Schizophrenia

Concepts of schizophrenia

Clinical descriptions

Concepts of etiology

Therapy

Perspective

BIBLIOGRAPHY

Schizophrenia constitutes the core problem of insanity. The conditions subsumed under the heading are among the most devastating to which man is heir, blighting him in the process of development or in the prime years of life and commonly leading to his progressive enclosure in an autistic world beset by delusion, hallucination, and fear of involvement with life and people. Because of the diverse manifestations, courses, and outcomes, schizophrenic reactions elude precise definition and concise description. They may be defined as gross failures to achieve or maintain integrated personality functioning in which a person, unable to cope with problems of living and irreconcilable conflicts, withdraws and seeks solutions by breaking through the confines imposed by the culture’s ways of thinking and reasoning and by regressing to a period of childhood when reality gave way to fantasy and when the self and others were not yet clearly distinguished. The condition tends to be self-perpetuating because the patient abandons testing his ideas in terms of how they help master his environment and promote collaborative interaction with others. However, restitutive efforts are usually made because a person cannot achieve an equilibrium as an isolate and because fears of uncontrollable impulses interfere with autistic gratification.

Incidence and prevalence. Schizophrenia is among the most common conditions leading to profound incapacitation. Of the daily hospital census in the United States of about 1.4 million patients, approximately one-fourth are hospitalized because of schizophrenia. Although the large majority are discharged within the first year after admission, the average length of stay is 13 years because a sizable number remain in hospitals from adolescence or early adulthood until death from old age or some disease. Incidence and prevalence can be estimated only very roughly because of the number of schizophrenic patients who are never hospitalized or even diagnosed and because of the vague boundaries of the condition. It has been estimated that between 14 and 20 of every 1,000 children born in the United States will be hospitalized at some time in their lives with an illness diagnosed as schizophrenia. A minimum annual prevalence rate of 290 per 100,000 has been suggested for Western societies (Lemkau Crocetti 1958). Surveys in New Haven (Hollingshead Redlich 1958) and in England (Brooke 1959) have shown that both incidence and prevalence are much higher among the lower socioeconomic segments of the population than among the upper-middle and upper classes. [SeeMental Disorders, article onEpidemiology.]

Concepts of schizophrenia

The profound divergencies of opinion concerning the nature, etiology, and treatment of schizophrenic conditions reflect differing concepts of the nature of human adaptation and integration more than they reflect divergent findings. Traditionally, psychiatrists have considered that the profound incapacitations of schizophrenic patients and, particularly, the disordered thinking that forms a critical aspect of the condition must be due to some unknown biological impairment—a structural defect of the brain or some hereditary metabolic or toxic factor influencing cerebral functioning. A large majority continues to believe that the high familial incidence indicates a hereditary predisposition that is affected by environmental factors, perhaps through aggravating a metabolic dysfunction. However, others consider schizophrenic reactions as an extreme type of aberrant personality functioning resulting from faulty and distorting child rearing in deviant family environments.

The way in which schizophrenia is conceptualized is not simply a matter of academic interest but of vital moment, as it influences the direction of scientific investigations and therapeutic efforts and, as will become apparent, has even profoundly influenced the clinical picture and course of the condition. The conviction that schizophrenia is a disease due to a biological impairment leads to concentration of research in neuropathological, physiological, and biochemical fields and has created therapeutic pessimism. This attitude has often contributed to the neglect of patients and, at times, virtually condemned them to crowded and impersonal institutions that aggravated their autistic withdrawal. Such orientation left little room for the participation of social scientists, other than in studies of the economic and social implications of a devastating disease. In contrast, the conceptualization of schizophrenia as a type of aberrant personality development has made it possible to consider schizophrenic reactions in the study of how the developmental process can go awry and thus perhaps to clarify critical issues concerning human integration and emotional homeostasis. Investigations of such matters as the role of language in human adaptation, of the family as a critical social institution that mediates between biological and cultural directives and between the individual and society, of the influence of social class on the incidence of mental illness and how it relates to child-rearing practices, of cross-cultural influences on personality development, and of the social and political structure of mental hospitals and the society’s system of caring for the ill, and numerous other areas of study become a vital part of the effort to understand, control, and treat schizophrenic reactions. Further, as schizophrenia constitutes one of the dominant unsolved health problems, the training of all physicians as well as of psychiatrists in particular will be affected profoundly by the conceptualization of the problems and the projection of an approach to their solution.

Historical considerations. The concept of schizophrenia as a clinical entity derives from Emil Kraepelin’s recognition in 1896 of the relationship between three forms of insanity—catatonia, described by K. Kahlbaum in 1863; hebephrenia, described by E. Hecker in 1871; and the deteriorating paranoid psychoses—and his uniting them under the designation “dementia praecox,” which B. Morel had used for a type of deteriorating adolescent psychosis. Kraepelin brought a degree of order to psychiatric taxonomy by differentiating dementia praecox from the manic-depressive psychoses. He emphasized the progressive course of dementia starting in youth and envisioned a distinct disease entity for which a specific structural pathology or causative agent would be found. The term “schizophrenia” was introduced by Eugen Bleuler in 1911, because not all sufferers from dementia praecox were youthful and not all became demented; it also served to emphasize the splitting of the psychic functions—the intellectual, affective, and conative—in these patients. Bleuler considered the possibility of a psychological causation but favored a hereditary etiology. He considered that the unknown etiologic agent produced primary symptoms of disturbances in associations, abnormalities of affect, emotional and intellectual ambivalence, and turning from reality to fantasy, as well as autism, whereas such symptoms as delusions, hallucinations, motor disorders, etc., were secondary and amenable to psychological treatment. He also stressed the intact capacities for perception, memory, and intellectual functioning that differentiate schizophrenia from the organic and toxic psychoses. In essence, he outlined the critical paradox of schizophrenic conditions: thought disorders form a critical aspect and diagnostic requisite, but the anatomical and physiological capacities for perceiving, thinking, and remembering remain intact. Together with Carl Gustav Jung, Bleuler brought psychoanalytic insights into the study of the psychology of schizophrenia. [See the biographies ofBleuler; Jung; Kraepelin.]

Adolf Meyer’s view. For the vast majority of psychiatrists throughout the world, the schizophrenic syndrome has remained essentially unchanged since the publication of Bleuler’s monograph (1911), although many have adhered more closely to Kraepelin’s concepts of a clear-cut disease entity, as the collected papers of the 1957 World Congress devoted to schizophrenia demonstrate (World Congress . . . 1959). However, Adolf Meyer, the dominant American contemporary of Bleuler, did not consider schizophrenia as an illness but as a reaction type that could be brought on by faulty “habit patterns,” including habits of thinking and relating (Meyer 1896-1937). For many years Meyer was almost the only important influence advocating longitudinal dynamic studies of life histories of schizophrenic patients, and he countered the prevailing therapeutic pessimism with his melioristic approach which advocated a type of psychotherapeutic management in a socializing milieu. Meyer is largely responsible for the different perspectives concerning schizophrenia held by many American psychiatrists in contrast to those of their Continental colleagues. [See the biography ofMeyer.]

Psychoanalysis. Even though Freud had excluded the treatment of schizophrenia from the province of psychoanalysis because he tacitly accepted an organic or toxic etiology and considered that the regression to narcissism prevented formation of a transference relationship, psychoanalysis still made many major contributions to understanding schizophrenic patients and their symptoms. Such concepts as narcissistic fixation and regression, the psychosexual stages of development, infantile sexuality, the withdrawal of cathexes (libidinal investment) from objects, primary process thinking, the interpretation of dreams, the exposition of the defense mechanisms —particularly those of projection and introjection— and of the importance of homosexuality to paranoid states, etc., opened the way for a dynamic understanding of schizophrenic patients and for comprehension of productions that previously had seemed to be the incomprehensible utterances of a diseased mind. Harry Stack Sullivan was among the first analysts who focused attention on the treatment of schizophrenic patients and whose psychoanalytic orientation was greatly modified by work with them. In the process he found need and use for contributions from various behavioral sciences. Sullivan (1924-1933) and his colleague Fromm-Reichmann (1948) were major forces in demonstrating by determined efforts that psychoanalytic therapy could be adapted to the treatment of schizophrenic patients. [See the biography ofSullivan.]

Clinical descriptions

The nature of the disorder varies widely. Most often schizophrenic reactions become manifest in the adolescent or young adult when the impact of sexual drives and the attainment of independence, an identity, and a way of life present critical problems. The young person may gradually and insidiously become increasingly withdrawn, preoccupied, and resistant to direction from others. He may avoid facing problems and relating to others by sleeping through much of the day. Sudden outbursts of irritability or hostility toward family members ward off intrusions. Rumination over personal and philosophical problems increases, and intellectualizations displace commitment and show of emotions. Differentiation from adolescent “identity crises” or other types of adolescent turmoil is difficult, and the future of the youth may hang in the balance. Gradually withdrawal becomes more extreme, indecision paralyzing, and ambivalence of feelings pronounced. Appearance and bodily hygiene may be neglected. Communication becomes vague, missing the mark and leaving the listener puzzled. Feelings of unreality and de-personalization are common. Self-direction is rescinded or paralyzed, allowing drive, impulse, and fantasy to gain increased motivating force. Control of drives and hostilities becomes a major preoccupation, while motivation is sought through interpreting coincidental events and reading meanings into people’s expressions and gestures. Then delusional solutions and hallucinated directives are found. Unacceptable feelings and impulses are projected onto others, who become malevolent figures. Hypochondriacal complaints are common and may reflect fears of transformation into the opposite sex. Increasingly the patient lives in an autistic world, gaining a sense of worth or even greatness through fantasy; he is also a prey to delusions of persecution and to terror lest homicidal, suicidal, or incestuous impulses overwhelm him. In some patients the first serious indication of the psychosis comes in an outbreak of panic over loss of control or over projected dangers. Frequently, when the patient can remain isolated or when he is neglected in an institution, habits and bodily care deteriorate, communications become disorganized and bizarre, and the patient comes to live in a world of delusion and hallucination. He exists in a state of almost living death, a nonparticipant in society and its conventions, virtually beyond the reach of therapeutic intervention. However, such outcomes are not inherent to schizophrenic reactions and need not occur, and with improved treatment they are becoming less common even in large institutions. The course and outcome vary widely and are influenced markedly by the treatment provided. Under average current conditions, approximately two-thirds of hospitalized patients will be discharged within 12 months: about half of these will remain reasonably well, while the remainder will have further serious difficulties and tend to have a downhill course. The outlook is poor for those who cannot be discharged within the first year. However, as less flagrant forms of schizophrenia are now diagnosed more often than formerly and as better treatment opportunities are available to some, the diagnosis need not imply so poor a prognosis. Schizophrenic reactions are most likely to occur in persons who have socialized poorly and who tend to be shy, introspective, somewhat eccentric, and, perhaps, compliantly overcon-scientious. Still, a fair proportion have not been notably schizoid, and some have been outgoing but impetuous individuals. Lifelong difficulties in socializing and an early progressive withdrawal decrease chances of recovery.

Types of schizophrenia. Conventionally, four types of schizophrenia are described. Actually, most patients can be fitted into these types only arbitrarily, showing admixtures of two or more types, with shifts in the dominant symptomatology over time. However, brief outlines of these subgroupings will serve to describe some of the different clinical pictures.

Catatonic schizophrenia. In catatonic schizophrenia extremes of violent motor excitement or rigid immobility dominate the picture. Onset is often abrupt. The patient may maintain difficult postures for hours, days, or months and requires complete care. Alternations between extreme excitement and rigidity may occur. Frequently these patients are in the midst of some mystical experience, believing themselves in heaven or hell; they are often immobile and refuse to speak because they believe any movement or word can produce a universal catastrophe. Although they may appear out of contact, they are aware of and sensitive to their surroundings. The prognosis is more favorable than for other types but unpredictable in the individual case. Chronic catatonic states, once fairly common, are becoming infrequent in modern hospitals.

Simple schizophrenia. Simple schizophrenia usually refers to a gradual withdrawal of interest and a progressive decline of responsible behavior with absence of commitment to a definite way of life. The potentialities shown in youth dissipate, and the patient idles about the home or becomes a vagrant, etc. Theoretically, Bleuler’s primary symptoms are present with minimal secondary symptoms; however, many patients given this diagnosis are delusional but noncommunicative about their delusions and hallucinations.

Hebephrenic schizophrenia. Hebephrenic schizophrenia usually starts in adolescence and progresses rapidly: the patient soon displays silly, impulsive, and disorganized behavior. Delusions and hallucinations are poorly organized and shifting. Speech is often fragmented and almost incomprehensible, marked by frequent intrusions of primary process material.

Paranoid schizophrenia. In paranoid schizophrenia delusions of a persecutory type dominate thought and behavior; ideas of reference are common and blend with auditory hallucinations. Meg-alomanic delusions relate to ideas of being the focus of widespread plots. The later in life the onset, the more likely it is that the delusions will be systematized and the reaction type approach the condition described under paranoid states. [SeeParanoid Reactions.]

Other subcategories. The current official nomenclature includes a schizoaffective type to cover the numerous patients who display an admixture of schizophrenic and manic-depressive symptoms: if these are considered separate entities, such patients would be suffering from both conditions. However, if schizophrenic reactions are regarded as a type of aberrant development leading to failures of personality integration, other such combined diagnoses will be used. Sociopathic youths can also be more or less schizophrenic; hypochon-driacal neuroses may shift to psychoses with somatic or hypochondriacal delusions; obsessive patients can decompensate with obsessive thoughts becoming increasingly bizarre and delusional. Further, although the typical schizophrenic reactions are readily diagnosed, there are no clear boundaries that delimit the use of the diagnosis.

Those who are reluctant to relinquish the concept of schizophrenia as a progressive deteriorating disease seek to distinguish between process and nonprocess schizophrenia or between schizophrenia and schizophreniform conditions (Langfeldt 1933): the patients who recover or who are amenable to psychotherapy, etc., are not considered as true schizophrenics and supposedly can be distinguished by their premorbid behavior, heredity, and symptomatology—a view not widely shared in the United States.

The diagnosis of pseudoneurotic schizophrenia (Hoch Polatin 1949) is used by some psychiatrists to indicate patients with panneurotic symptomatology who are not amenable to psychotherapy because they are really schizophrenic, but others consider these as “borderline” patients whose neurotic symptoms form a defense against personality disorganization. Borderline schizophrenia refers to patients who maintain a tenuous integration with meager defenses against incursions of primitive impulses and strange primary process material into consciousness.

Childhood schizophrenia refers to cases occurring before adolescence. It is not clear if cases occurring early in childhood are related to the adult condition. Early infantile autism is a puzzling illness that occurs in the first few years of life; the child begins to display peculiar repetitive behavior and regresses, paying little attention to other persons. Some of these children clearly suffer from brain anomalies or brain damage; others have been raised by unempathic, intellectualizing parents. These conditions cannot be discussed adequately in this section. [SeeMental Disorders, article onchildhood mental disorders.]

The confusions concerning nomenclature have been presented because the various terms are in common usage but also because they reflect the difficulties and ambiguities in the field. Terms may be used in the literature with a certainty that can be misleading, leaving the inexperienced person— and even the experienced one—feeling ignorant rather than perplexed when he cannot make a clear-cut diagnosis.

Concepts of etiology

Impairment of brain functioning. The conviction that such profound personality disorganizations, marked by disordered thinking and often progressing to an almost vegetative state of existence, must reflect impairment of brain functioning has led to intensive investigations of post-mortem and biopsy sections of the brain and of every endocrine, toxic, and biochemical factor that might conceivably affect cerebral functioning. The erroneous assumption that insulin coma therapy cured schizophrenia led to an upsurge of such studies in the 1930s and 1940s, and currently the meliorating effects of the phenothiazine drugs have provided renewed impetus. Investigators have again and again reported some biochemical factor they consider specific to schizophrenia, and each of these findings has been invalidated sooner or later. A number of these factors have turned out to be related to such things as dietary inadequacies or are concerned with physiological disturbances secondary to chronic emotional disturbances or to prolonged inactivity or some other influence of chronic hospitalization.

Neuroanatomical investigations. None of the numerous reports of an abnormality of the brain has been validated. The similarities of the personalities and developmental histories of patients with psychomotor epilepsy and schizophrenia form an interesting lead that is under study.

Endocrine investigations. Although the thyroid, pituitary, gonadal, pineal, and adrenal cortical and medullary secretions have all been implicated, no evidence has held up. The intriguing hypothesis that epinephrine undergoes an anomalous breakdown into psychotoxic substances is being pursued (Hoffer 1964), but recent evidence does not bear out the initial enthusiasm.

Biochemical investigations. Recently emphasis has been directed to the study of brain amines and indole excretion, and to psychotogenic agents such as LSD-25 and the supposedly psychotogenic extracts of schizophrenic serum. Various theories relating several such factors have been proposed. Intensive work is advancing knowledge of brain chemistry and fosters hope for future discoveries pertinent to schizophrenia, but recent premature enthusiasms indicate a need for more carefully controlled and validated work before publication. [SeeMental disorders, article onbiological aspects.]

Genetic hypothesis. The high familial incidence of schizophrenia had led to virtual acceptance of the belief that some genetically transmitted factor plays an important role in the etiology of schizophrenia [see mental disorders, article on genetic aspects]. It has been primarily the evidence from twin studies that seemed to demand acceptance of a strong hereditary influence. Until very recently all twin studies reported a much higher concordance rate in identical twins than in same-sexed fraternal twins or siblings—as high as 86 per cent in identical as against 17 per cent in same-sexed fraternal twins. Lately, several investigators noted puzzling inconsistencies in the data. The only two studies of all twins born within a given span of time rather than of samples of hospitalized patients fail to validate the earlier findings. A survey of all male twins born in Finland between 1930 and 1935 found that none of the 16 schizophrenic patients among the identical twins had a schizophrenic co-twin (Tienari 1963). Studies in Norway of an even larger sample, although still incomplete, indicate that concordance rates for identical twins will not be much higher than for same-sexed siblings (Kringlen 1964). It appears as if the striking results of prior twin studies were due to sampling errors and that this basis for the genetic hypothesis of schizophrenia has been badly shaken.

Family environment. A high familial incidence of personality traits or illnesses has often led to erroneous overemphasis of genetic factors. Attention has been directed increasingly to the role of the family environment in producing schizophrenic offspring. Psychoanalytic theory, in considering schizophrenia related to fixations at the oral stage of development, drew attention to failures in the earliest mother-child transactions. As early as 1924, Sullivan emphasized the noxious influence of certain mothers on the development of their schizophrenic sons, both directly and because of their attitudes toward their husbands (1924-1933). Considerable etiologic significance has been given to the “schizophrenogenic mother” who is either aloof, unempathic, and unable to cathect in the child properly or, more typically, cannot establish boundaries between herself and the child, engulfing and controlling a child she needs to complete her life. Studies since 1949 (Lidz et al. 1965) have revealed deficiencies and abnormalities in the total intrafamilial environment. The fathers are frequently just as severely disturbed as the mothers. The family is split by enduring conflict between the parents in which each demolishes the worth of the other to the children, or the family transactions are distorted because one parent acquiesces to the spouse’s strange ways of rearing children and patterning the family life. The generation roles within the family are confused in a variety of ways such as parental rivalry with a child or parental dependency upon an immature child, including heterosexual or homosexual incestuous proclivities. Parents fail to adhere to their respective sex-linked roles, either because of homosexual tendencies or through reversing maternal and paternal roles, or because a mother cannot fill an affectional-expressive role or a father an instrumental role. The parent of the same sex as the child who becomes schizophrenic does not form an adequate model for identification, a situation that is often aggravated because this parent’s worth is undercut by the spouse.

Communication within the family is always disturbed and often clearly irrational or paralogical. The intrafamilial culture may deviate markedly from that of the society into which the child must eventually emerge. These families teach or indirectly inculcate irrationality, providing a poor foundation in reality testing and for understanding verbal and nonverbal communications outside of the family. The schizophrenic patient’s siblings are almost always seriously affected: more are psychotic than are reasonably well-integrated, and with rare exception their occasional “normality” is achieved at the price of serious constriction of the personality.

The finding that schizophrenic patients always grow up in seriously disturbed families forms the most consistent lead concerning the etiology of schizophrenia. Essentially similar phenomena have been reported by research groups in many different countries. In conceptualizing how such disturbed family transactions can lead to schizophrenia in an offspring, some investigators focus primarily upon how the disturbed patterns of communication foster the schizophrenic thought disorder. The “double bind” hypothesis (Bateson et al. 1956) notes how the patient is habitually caught in a bind because a parent covertly sends conflicting messages that perplex and paralyze, causing him to be rebuffed whichever way he responds; or he is caught between the opposing needs and demands of his two parents, and satisfying either parent provokes rejection by the other. Various other communication problems have been noted: the ways in which the child is taught to deny or ignore what should be obvious; the distortions of meanings to support a parent’s tenuous emotional equilibrium; the fostering of distrust in the utility of verbal communications; the teaching of eccentric or delusional beliefs; the blurring of the system of meanings and constructs by inconsistent reinforcement by parents, etc. (Lidz et al. 1965). The amorphous or fragmented nature of the thinking and communicating of one or both parents has been carefully documented (Wynne Singer 1963). Studies of the family communication patterns clarify why the patient suffers from a thought disorder and how such resultant impairments in thinking and communicating create profound disturbances in ego functioning.

The family disturbances, however, clearly affect the child’s development deleteriously in other significant ways. A broader approach to the problem takes cognizance of how failures of parental nur-turance, particularly the mother’s difficulties in relating to the child, interfere with the development of adequate autonomy; how the disturbances in the family structure distort the structuring of the child’s personality by improper channeling of drives, through confusing child and parent roles, by creating confusions in sexual identity, by impeding proper resolution of the oedipal situation, etc.; as well as of how parents’ failure to transmit adequately basic adaptive or instrumental techniques of the culture, including its system of meanings, impairs ego functioning and socializing capacities (Lidz et al. 1965).

The family studies have thus far been largely exploratory, paving the way for the formulation of hypotheses that are now being studied with more rigorous methodology. Although not definitive, they have served to move research concerning the etiology of schizophrenia out of the frustrating whirlpool in which it had been caught. Many puzzling aspects of schizophrenia now seem far more comprehensible. The findings interdigitate with those of other approaches, such as studies of the relationship between social class and incidence of schizophrenia, twin studies, and psychoanalytic concepts of developmental dynamics. The knowledge gained from these studies has also had a marked impact upon therapy, particularly through drawing attention to the need to consider the family as a unit rather than simply to focus upon the individual patient.

Therapy

Despite the absence of any specific method of treatment, marked changes have taken place in the therapy of schizophrenic patients since 1940. Perhaps the most important change has been the gradual but progressive abandonment of the defeatist attitude concerning schizophrenia that had pervaded most of psychiatry since the mid-nineteenth century. Although debates have waged concerning the value of insulin coma, electroshock, frontal lobotomy, milieu therapy, and various forms of individual and group psychotherapy, psychiatrists and other personnel finding something they could do or try to do became interested in the patients, and the patients responded. It became apparent to increasing numbers of psychiatrists that schizophrenic patients need not follow a downhill course, and that many of the extreme manifestations were products of neglect and virtual abandonment in impersonal institutions. The enormity of the problem of caring for and attempting to treat the masses of institutionalized patients has been overwhelming, and adequate treatment for any other than selected patients has had to await reorganizations of hospital systems and the training of the necessary personnel.

Therapeutic efforts must be suited to the patient, the facilities available, and the therapist’s abilities. Whereas the prognosis for schizophrenic reactions collectively is generally discouraging, the outlook for the individual patient, particularly if treatment begins soon after symptoms appear and intensive care can be provided, may be regarded hopefully.

“Organic” treatments. Although insulin coma therapy, introduced in 1933, did much to revive interest in the treatment of schizophrenic patients, it has now been virtually discarded, its apparent efficacy having resulted from the increased attention to patients it required. Electric convulsive treatments are of occasional value as a means of quieting extremely excited patients. Various tran-quilizing drugs, particularly the phenothiazines, have largely replaced other “organic” treatments. The phenothiazines serve to lessen anxiety and agitation and probably diminish distraction by extraneous stimuli and primary process intrusions. Trifluoperazine may be particularly useful in diminishing hallucinations. An array of psychotropic drugs is now available, and opinions differ as to the merits of each. Properly controlled experiments on the relative worth of these medications are extremely difficult to conduct. It seems reasonably certain that many patients can return to or remain in the community largely because of these agents. A major influence of tranquilizing drugs has been indirect; they have helped quiet the wards in mental institutions and provided a means of controlling seriously disturbed patients. This has helped produce great changes in mental hospitals through unlocking doors, permitting patients greater freedom, and allowing the staff time and opportunity to improve the therapeutic milieu. [SeeMental disorders, treatment of, article Onsomatic treatment.]

Milieu therapy. Establishing a suitable therapeutic hospital milieu has altered the prognosis for schizophrenic patients as much as the tranquilizing drugs, but in all except certain select institutions, reorganization had to await the quieting effects of the shock therapies and then the tranquilizers. Milieu therapy seeks to counter schizophrenic patients’ tendencies to withdraw; it also fosters socialization, promotes responsibility, and provides retraining in interpersonal relationships. The therapy includes a gamut of measures ranging from discarding restraints; minimizing isolation; giving attentive care and interest; fostering socializing, educational, and occupational activities; and providing group therapy to holding patient-staff meetings and setting up patient government to provide channels of communication and to encourage responsibility for the self and others. Opening the doors of hospitals has a salutary influence and can markedly change the attitudes of both patients and staff, but some patients who are afraid of their impulsivity, aggressions, or suicidal tendencies feel more secure and can socialize more readily when protected within a limited area until they are ready to assume responsibility for their actions.

As schizophrenic patients tend to regress, withdraw, and become passively dependent in institutions, there has been a movement to return such patients to the community as soon as feasible or to attempt to keep them out of hospitals altogether. On the other hand, efforts are often made to promote early hospitalization, for the chances of recovery are greater if treatment starts before symptoms become well established and if the patient can be removed from a pathogenic environment. The paradox revolves around the nature of the treatment a hospital can offer; optimally a hospital should be able to counter regressive tendencies. As yet, relatively few institutions can provide intensive care and treatment that seeks to promote essential- personality change rather than mere remission from a psychotic state.

Psychotherapy. Establishing a relationship to another person often—perhaps always—provides the impetus and forms the bridge for the schizophrenic patient’s return from psychotic withdrawal. The crux of the initial phases of psychotherapeutic work with these patients is the therapist’s use of himself to gain the patient’s trust and willingness to risk relating again despite the shattering dis-illusionments of the past. A persistent warm and honest interest by an untrained person may suffice and succeed where a highly trained but intel-lectualized and uncommitted therapist fails. Schizophrenic patients are usually highly sensitive to pretense, to being used by another person, and to another person’s withdrawal in the face of their intense needs or their hostilities. Usually, however, considerable skill and understanding of schizophrenic patients are required. Trust follows upon understanding, understanding requires communication, and the therapist faces the task of establishing communication across barriers imposed by the patient’s idiosyncratic language usage, his personalized metaphor, his efforts to conceal and yet convey, the delusions and hallucinatory interruptions, and the projections of the patient’s thoughts and feelings onto the therapist, etc. The therapist must be prepared and able to counter or weather the patient’s flights into withdrawal, particularly when the patient feels on the verge of trusting and becoming involved—setbacks that test the therapist’s commitment. Bringing a patient out of his psychotic regression and withdrawal can be a very real and rewarding achievement, but something that often occurs without specific psychotherapy; the process is more successful when the therapist is a focal point in a proper therapeutic milieu that counters the patient’s regression in many ways than when the emphasis is solely upon the individual psychotherapy.

Psychotherapy of schizophrenia usually implies more than bringing the patient out of the psychotic episode or into socially acceptable behavior. It often involves the effort to promote profound personality changes through psychoanalytically oriented interpersonal transactions. Such work with schizophrenic patients differs markedly from the analysis of psychoneurotic patients. It seeks to strengthen ego functioning through fostering a more cohesive identity, firmer boundaries between the self and others, and control of primitive impulses. Treatment almost always includes extensive re-evaluation of parental figures and efforts to modify the sway of sabotaging parental introjects. The intense nature of the transference relationship once it is established, together with the frangibility of the relationship, places great demands upon the therapist. It is a task for highly skilled therapists with specific experience and training in the field and will not be discussed here. The effectiveness of intensive psychotherapy with schizophrenic patients cannot be evaluated in statistical terms: the belief in its value derives from the excellent results obtained with a number of individuals and from the meaningfulness of the material gained in the process. Much depends on the specific therapist as well as on the specific patient. The aims of such work are directed in part toward the future—to increasing knowledge and improving techniques. [SeeClinical Psychology; Mental Disorders, Treatment of, especially the article onPsychological Treatment; Psychiatry.]

Family therapy. Recent advances in understanding of the pathology in the schizophrenic’s family of origin have brought the family into the therapeutic efforts in a variety of ways. Social workers or psychiatrists have worked with parents individually or in groups to allay their anxiety and guilt; to counter the common tendency of parents to interfere with or disrupt the patient’s therapy; to modify the parents’ attitudes toward each other as well as toward the patient; and to foster more direct and forthright communication. With some families a major effort is made to prevent exclusion of a hospitalized patient and withdrawal of interest in him and in others to help prevent disintegration of the family after the patient has been hospitalized. Conjoint family therapy in which parents and patient or the entire family are seen in group sessions has been found advantageous. The therapist has an opportunity to view directly the nature of the disturbed relationships and communications; the patient may gain a new perception of his parents and an appreciation of their limitations and idiosyncrasies; and other family members may recognize their own roles in provoking or continuing the patient’s illness, gain insights concerning the family transactions, and begin to relate differently. Although some psychiatrists consider conjoint family therapy to be the optimal treatment procedure, others use it as an important adjunct to alternative therapeutic measures.

Perspective

The disagreements between virtually all schools of psychiatry concerning the nature and etiology of schizophrenia have interfered with the presentation of a coherent and cohesive approach to the problem. Although schizophrenia is traditionally considered a disease of unknown etiology, a great deal is now known about the developmental problems and the dynamic psychopathology of these patients and about the family environments that tend to produce them. Man is unique in the degree that his adaptation rests on a lengthy period of dependency upon parental figures during which he must assimilate the instrumental techniques of his culture to implement his inborn adaptive capacities. There are countless chances for misdirection, confusion, and conflict to arise in the process. The very mechanism that permits his inordinate adaptability contains a major vulnerability. He depends upon language and a coherent way of thinking to guide him into the future and on an ability to communicate to enable collaborative interaction. Yet linguistic meanings and a system of logic are not inborn but acquired as a means of problem solving by communication with others and by sorting out life experiences. How correctly meanings are learned and how firmly they become ingrained depend largely on the parental tutors—the consistency of their communications as an aid to problem solving and the emotional relationships between parents and child. There are countless ways in which the enculturation process can go wrong. When a person is caught in insoluble conflicts, when a path into the future is barred, when even regression serves little because the persons upon whom one could depend are distrusted or feared, there is still a way. One can alter the perception of his own needs and motives and those of others. One can abandon causal logic, change his internal representation of events, retreat to a period of childhood when reality gave way to fantasy, and cut off movement toward a realistic future; that is, one can become schizophrenic. This path is so clearly open to man, particularly to those who have had confused or confusing guides to follow into adulthood and have received poor foundations in meaning systems and reality testing, or who have actually been trained to irrational ways in childhood, that conditions such as schizophrenia must be expected as anomalies of the human developmental process. The acceptance of such a theory that schizophrenic reactions result from anomalous socialization processes and that the family forms the primary enculturating agency provides numerous guides for research and therapy, and it directs the psychiatrist toward increased collaboration with behavioral scientists.

Theodore Lidz

[Directly related are the entriesMental disorders; Psychosis. Other relevant material may be found inMental disorders, treatment of; Psychiatry; Psychoanalysis; and in the biographies ofKraepelin; Meyer; Sullivan.]

BIBLIOGRAPHY

Alanen, Y. O. 1958 The Mothers of Schizophrenic Patients: A Study of the Personality and the Mother-Child Relationship of 100 Mothers and the Significance of These Factors in the Pathogenesis of Schizophrenia in Comparison With Heredity. Acta psychiatrica scandinavica 33 (Supplement 124).

Akieti, Silvano 1955 Interpretation of Schizophrenia. New York: Brunner. A readable and cogent presentation of a modern dynamic approach.

Bateson, Gregory et al. 1956 Toward a Theory of Schizophrenia. Behavioral Science 1:251-264.

Bellak, Leopold (editor) 1958 Schizophrenia: A Review of the Syndrome. New York: Logos. Reviews work in the field between 1946 and 1956; contains 4,000 references.

Bleuler, Eugen (1911) 1950 Dementia Praecox: Or, the Group of Schizophrenias. New York: International Universities Press. Still an outstanding work on the topic. Includes an extensive BIBLIOGRAPHY to 1950. First published as “Dementia Praecox oder die Gruppe der Schizophrenien” in Aschaffenburg’s Handbuch der Psychiatric.

Brody, Eugene B.; and Redlich, F. C. (editors) 1952 Psychotherapy With Schizophrenics. New York: International Universities Press.

Brooke, Eileen M. 1959 National Statistics in the Epidemiology of Mental Illness. Journal of Mental Science 105:893—908. Now called the British Journal of Psychiatry. CAMERON, NORMAN A. 1938 Reasoning, Regression and Communication in Schizophrenics. Psychological Monographs. Vol. 50, no. 1. Columbus, Ohio: Ohio State University. -* A classic study of schizophrenic thinking.

Delay, Jean; Denikeh, P.; and Green, A. 1957-1962 Le milieu familial des schizophrenes. 3 parts. En-cephale 46:189-232; 49:1-21; 51:5-73. Part 1: Position du probleme, 1957. Part 2: Methodes d’ap-proche, 1960. Part 3: Resultats et hypotheses, 1962.

Freeman, Thomas; Cameron, John L.; and McGhie, Andrew 1958 Chronic Schizophrenia. New York: International Universities Press.

Fromm-Reichmann, Frieda 1948 Notes on the Development of Treatment of Schizophrenics by Psychoanalytic Psychotherapy. Psychiatry 11:263-273.

Hoch, Paul; and Polatin, Phillip 1949 Pseudoneu-rotic Forms of Schizophrenia. Psychiatric Quarterly 23:248-276.

Hoffer, Abram 1964 The Adrenochrome Theory of Schizophrenia: A Review. Diseases of the Nervous System 25:173-178.

Hollingshead, August B.; and Reduce, F. C. 1958 Social Class and Mental Illness: A Community Study. New York: Wiley.

Jackson, Don D. (editor) 1960 The Etiology of Schizophrenia. New York: Basic Books. → An excellent collection of papers on various contemporary theories.

Kasanin, J. S. (editor) 1944 Language and Thought in Schizophrenia. Berkeley and Los Angeles: Univ. of California Press. Brief articles by various authorities that can serve as an introduction to the topic.

Kringlen, Einar 1964 Schizophrenia in Male Monozy-gotic Twins. Acta psychiatrica scandinavica 40 (Supplement 178):1-76.

Langfeldt, G. 1933 Some Points Regarding the Symptomatology and Diagnosis of Schizophrenia. Acta psychiatrica et neurologica scandinavica Supplement 80:7—26. → Now called Acta psychiatrica scandinavica.

Lemkau, Paul V.; and Crocetti, Guroo M. 1958 Vital Statistics of Schizophrenia. Pages 64-81 in Leopold Bellak (editor), Schizophrenia: A Review of the Syndrome. New York: Logos.

Lidz, Theodore; Fleck, Stephen; and Coknelison, Alice R. 1965 Schizophrenia and the Family. New York: International Universities Press. → Collected papers of an intensive study of the intrafamilial environment of schizophrenic patients.

Meyer, Adolf (1896-1937)1951 Collected Papers. Volume 2: Psychiatry. Baltimore: Johns Hopkins Press. For the origins of the genetic-dynamic approach, see the chapters “Dementia Praecox” and “Paranoia” on pages 413-560.

Rees, W. Linford 1957 Physical Characteristics of the Schizophrenic Patient. Pages 1-14 in Derek Richter (editor), Schizophrenia: Somatic Aspects. London: Pergamon.

Die Schizophrenie. 1932 Volume 9, special part 5 in Karl Wilmanns (editor), Handbuch der Geistes-krankheiten. Berlin: Springer. An authoritative source for the German approach in the Kraepelinian tradition. Contains an outstanding BIBLIOGRAPHY.

Singer, Margaret T.; and Wynne, Lyman C. 1965a Thought Disorder and Family Relations of Schizophrenics: III. Methodology Using Protective Techniques. Archives of General Psychiatry 12:187-200.

Singer, Margaret T.; and WYNNE, LYMAN C. 1965b Thought Disorder and Family Relations of Schizophrenics: IV. Results and Implications. Archives of General Psychiatry 12:201-212.

Sullivan, Harry Stack (1924-1933) 1962 Schizophrenia as a Human Process. New York: Norton.

Symposium international sur la psychotherapie de la schizophrenic. 1957 Acta psychotherapeutica, psychosomatica et orthopaedagogica 5:99-360.

Symposium ON Schizophrenia, San Francisco, 1958 1959 Schizophrenia: An Integrated Approach. Edited by Alfred Auerbach. New York: Ronald Press.

Tienari, P. 1963 Psychiatric Illnesses in Identical Twins. Acta psychiatrica scandinavica 39 (Supplement 171). The whole supplement is devoted to Tienari’s study.

World Congress OF Psychiatry, Second, Zurich, 3957 1959 Report. 4 vols. Zurich: Fiissli.

Wynne, Lyman C.; and Singer, Margaret T. 1963 Thought Disorder and Family Relations of Schizophrenics. 2 parts. Archives of General Psychiatry 9: 191-206. → Part 1: A Research Strategy. Part 2: A Classification of Forms of Thinking.

Schizophrenia

Definition

Description

Causes and symptoms

Demographics

Diagnosis

Treatments

Prognosis

Prevention

Resources

Definition

Schizophrenia is a psychotic disorder or group of disorders whose symptoms include disturbances in thinking, emotional responsiveness, and behavior. Schizophrenia is the most chronic and disabling of the severe mental disorders, associated with abnormalities of brain structure and function, disorganized speech and behavior, delusions , and hallucinations . It is considered a psychotic disorder or a psychosis .

Description

People diagnosed with schizophrenia do not always have the same set of symptoms; in addition, a given patient’s symptoms may change over time. Since the nineteenth century, doctors have recognized different subtypes of the disorder, but no single classification system has gained universal acceptance. Some psychiatrists prefer to speak of schizophrenia as a group or family of disorders (“the schizophrenias”) rather than as a single entity. A standard professional reference, The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) acknowledges that its present classification of subtypes is not fully satisfactory for either clinical or research purposes; and states that “alternative subtyping schemes are being actively investigated.”

E. FULLER TORREY (1937&)

Psychiatrist E. Fuller Torrey, who has been especially involved in researching and treating schizophrenia, is the author of numerous works of nonfiction dealing with mental illness. In his first major work, The Mind Game: Witchdoctors and Psychiatrists, he compares modern psychiatric practices to those of primitive witchdoctors, and in The Death of Psychiatry he alleges that modern psychiatry has misdiagnosed maladjustment as mental illness. In the latter work, Torrey advocates support systems for the socially traumatized and recommends neurological help for the truly unbalanced.

Torrey’s other writings include Why Did You Do That? Rainy Day Games for a Post-Industrial Society, a game-book in which he counsels readers on the importance of recognizing biological, sociological, and psychological factors in assessing human behavior. He also

wrote Surviving Schizophrenia: A Family Manual, in which he supplements a detailed account of the disease’s genetic origin and symptoms with testimony from schizophrenics. Surviving Manic Depression: A Manual on Bipolar Disorder for Patients, Families, and Providers, written with Michael B. Knable, discusses changes in the classification and approach to manic depression, or bipolar disorder, over the years. They also discuss reasons why many people who suffer from the effects of the disorder have not been treated. The authors include material on the risk factors and causes of manic depression as well as details on the variety of treatments available. Beatty concluded that the work is an “important book that may be useful for years.” Library Journal critic Mary Ann Hughes felt that Surviving Manic Depression is “the best general book available on the subject” of bipolar disorder and its treatment.

The symptoms of schizophrenia can appear at any time after age six or seven, although onset during adolescence and early adult life is the most common pattern. There are a few case studies in the medical literature of schizophrenia in children younger than five, but they are extremely rare. Schizophrenia that appears after age 45 is considered late-onset schizophrenia. About 1–2% of cases are diagnosed in patients over 80.

The onset of symptoms in schizophrenia may be either abrupt (sudden) or insidious (gradual). Often, however, it goes undetected for two to three years after the onset of diagnosable symptoms, because the symptoms occur in the context of a previous history of cognitive and behavioral problems. The patient may have had panic attacks, social phobia , or substance abuse problems, any of which can complicate the process of diagnosis . In most cases, however, the patient’s first psychotic episode is preceded by a prodromal (warning) phase, with a variety of behaviors that may include angry outbursts, withdrawal from social activities, loss of attention to personal hygiene and grooming, anhedonia (loss of one’s capacity for enjoyment), and other unusual behaviors. The psychotic episode itself is typically characterized by delusions, which are false but strongly held beliefs that result from the patient’s inability to separate real from unreal events, and hallucinations, which are disturbances of sense perception. Hallucinations can affect any of the senses, although the most common form of hallucination in schizophrenia is auditory (“hearing voices”). Autobiographical accounts by people who have recovered from schizophrenia indicate that these hallucinations are frightening and confusing. Patients often find it difficult to concentrate on work, studies, or formerly pleasurable activities because of the constant “static” or “buzz” of hallucinated voices.

There is no “typical” pattern or course of the disorder following the first acute episode. The patient may never have a second psychotic episode; others have occasional episodes over the course of their lives but can lead fairly normal lives otherwise. About 70% of patients diagnosed with schizophrenia have a second psychotic breakdown within five to seven years after the first one. Some patients remain chronically ill; of these, some remain at a fairly stable level while others grow steadily worse and become severely disabled.

About 20% of patients with schizophrenia recover the full level of functioning that they had before the onset of the disorder, according to NIMH statistics; but the remaining 80% have problems reintegrating into mainstream society. These patients are often underachievers in school and in the workplace, and they usually have difficulty forming healthy relationships with others. The majority (60–70%) of patients with schizophrenia do not marry or have children, and most have very few friends or social contacts. The impact of these social difficulties as well as the stress caused by the symptoms themselves is reflected in the high suicide rate among patients with schizophrenia. About 10% commit suicide within the first 10 years after their diagnosis—a rate 20 times higher than that of the general population.

Subtypes of schizophrenia

The DSM-IV-TR specifies five subtypes of schizophrenia:

• Paranoid type. The central feature of this subtype is the presence of auditory hallucinations or delusions alongside relatively unaffected mood and cognitive functions. The patient’s delusions usually involve persecution, grandiosity, or both. About a third of schizophrenias diagnosed in the United States belong to this subtype.
• Disorganized type. The core features of this subtype include disorganized speech, disorganized behavior, and flat or inappropriate affect. The person may lose the ability to perform most activities of daily living, and may also make faces or display other oddities of behavior. This type of schizophrenia was formerly called “hebephrenic” (derived from the Greek word for puberty), because some of the patients’ behaviors resemble adolescent silliness.
• Catatonic type. Catatonia refers to disturbances of movement, whether remaining motionless for long periods of time or excessive and purposeless movement. The absence of movement may take the form of catalepsy, which is a condition in which the patient’s body has a kind of waxy flexibility and can be reposi-tioned by others; or negativism, a form of postural rigidity in which the patient resists being moved by others. A catatonic patient may assume bizarre postures or imitate the movements of other people.
• Undifferentiated type. Patients in this subtype have some of the characteristic symptoms of schizophrenia but do not meet the full criteria for the paranoid, disorganized, or catatonic subtypes.
• Residual type. Patients in this category have had at least one psychotic episode, continue to have some negative symptoms of schizophrenia, but do not have current psychotic symptoms.

Cultural variables

There appear to be some differences across cultures in the symptoms associated with schizophrenia. The catatonic subtype appears to be more common in non-Western countries than in Europe or North America. Other studies indicate that persons diagnosed with schizophrenia in developing countries have a more acute onset of the disorder but better outcomes than patients in the industrialized countries.

Causes and symptoms

Causes

Schizophrenia is considered the end result of a combination of genetic, biochemical, developmental, and environmental factors, some of which are still not completely understood. There is no known single cause of the disorder.

Researchers have known for many years that first-degree biological relatives of patients with schizophrenia have a 10% risk of developing the disorder, as compared with 1% in the general population. The monozygotic (identical) twin of a person with schizophrenia has a 40–50% risk. The fact that this risk is not higher, however, indicates that environmental as well as genetic factors are implicated in the development of schizophrenia.

Some specific regions on certain human chromosomes have been linked to schizophrenia. However, these regions tend to vary across ethnic groups. Scientists are inclined to think that the genetic factors underlying schizophrenia vary across different ethnic groups, so that it is highly unlikely that susceptibility to the disorder is determined by only one gene. Because of this, schizophrenia is considered a polygenic disorder.

There is some evidence that schizophrenia may be a type of developmental disorder related to the formation of faulty connections between nerve cells during fetal development. The changes in the brain that normally occur during puberty then interact with these connections to trigger the symptoms of the disorder. Other researchers have suggested that a difficult childbirth may result in developmental vulnerabilities that eventually lead to schizophrenia.

In early 2002, researchers at the NIMH demonstrated the existence of a connection between two abnormalities of brain functioning in patients with schizophrenia. The researchers used radioactive tracers and positron emission tomography (PET) to show that reduced activity in a part of the brain called the prefrontal cortex was associated in the patients, but not in the control subjects, with abnormally elevated levels of dopamine in the striatum. High levels of dopamine are related to the delusions and hallucinations of psychotic episodes in schizophrenia. These findings suggest that treatment directed at the prefrontal cortex might be more effective than present anti-psychotic medications, which essentially target dopamine levels without regard to specific areas of the brain.

Certain environmental factors during pregnancy are also associated with an increased risk of schizophrenia in the offspring. These include the mother’s exposure to starvation or famine, influenza during the second trimester of pregnancy, and Rh incompatibility in a second or third pregnancy.

Some researchers are investigating a possible connection between schizophrenia and viral infections of the hippocampus, a structure in the brain that is associated with memory formation and the human stress response. It is thought that damage to the hippocampus might account for the sensory disturbances found in schizophrenia. Another line of research related to viral causes of schizophrenia concerns a protein deficiency in the brain.

Environmental stressors related to home and family life (e.g., parental death or divorce, family dysfunction) or to separation from the family of origin in late adolescence (e.g., going away to college or military training; marriage) may trigger the onset of schizophrenia in individuals with genetic or psychological vulnerabilities.

Symptoms

The symptoms of schizophrenia are divided into two major categories: positive symptoms , which are defined by DSM-IV-TR as excesses or distortions of normal mental functions; and negative symptoms, which represent a loss or reduction of normal functioning. Of the two types, the negative symptoms are more difficult to evaluate because they may be influenced by a concurrent depression or a dull and unstimulating environment, but they account for much of the morbidity (unhealthiness) associated with schizophrenia.

POSITIVE SYMPTOMS

The positive symptoms of schizophrenia include four so-called “first-rank” or Schneiderian symptoms, named for a German psychiatrist who identified them in 1959:

• Delusions. A delusion is a false belief that is resistant to reason or to confrontation with actual facts. The most common form of delusion in patients with schizophrenia is persecutory; the person believes that others—family members, clinical staff, terrorists, etc.—are “out to get” them. Another common delusion is referential, which means that the person interprets objects or occurrences in the environment (a picture on the wall, a song played on the radio, laughter in the corridor, etc.) as being directed at or referring to them.
• Somatic hallucinations. Somatic hallucinations refer to sensations or perceptions about one’s body that have no known medical cause, such as feeling that snakes are crawling around in one’s intestines or that one’s eyes are emitting radioactive rays.
• Hearing voices commenting on one’s behavior or talking to each other. Auditory hallucinations are the most common form of hallucination in schizophrenia, although visual, tactile, olfactory, and gustatory hallucinations may also occur. Personal accounts of recovery from schizophrenia often mention “the voices” as one of the most frightening aspects of the disorder.
• Thought insertion or withdrawal. These terms refer to the notion that other beings or forces (God, aliens from outer space, the CIA, etc.) can put thoughts or ideas into one’s mind or remove them.

Other positive symptoms of schizophrenia include:

• Disorganized speech and thinking. A person with schizophrenia may ramble from one topic to another (derailment or loose associations); may give unrelated answers to questions (tangentiality); or may say things that cannot be understood because there is no grammatical structure to the language (“word salad” or incoherence).
• Disorganized behavior. This symptom includes such behaviors as agitation; age-inappropriate silliness; inability to maintain personal hygiene; dressing inappropriately for the weather; sexual self-stimulation in public; shouting at people, etc. In one case study, the patient played his flute for hours on end while standing on top of the family car.
• Catatonic behavior. Catatonic behaviors have been described with regard to the catatonic subtype of schizophrenia. This particular symptom is sometimes found in other mental disorders.

NEGATIVE SYMPTOMS

The negative symptoms of schizophrenia include:

• Blunted or flattened affect. This term refers to loss of emotional expressiveness. The person’s face may be unresponsive or expressionless, and speech may lack vitality or warmth.
• Alogia. Alogia is sometimes called poverty of speech. The person has little to say and is not able to expand on their statements. A doctor examining the patient must be able to distinguish between alogia and unwillingness to speak.
• Avolition. The person is unable to begin or stay with goal-directed activities. They may sit in one location for long periods of time or show little interest in joining group activities.
• Anhedonia. Anhedonia refers to the loss of one’s capacity for enjoyment or pleasure.

OTHER SYMPTOMS AND CHARACTERISTICS

Although the following symptoms and features are not diagnostic criteria of schizophrenia, most patients with the disorder have one or more:

• Dissociative symptoms, particularly depersonaliza-tion and derealization.

• Anosognosia. This term originally referred to the inability of stroke patients to recognize their physical disabilities, but is sometimes used to refer to lack of insight in patients with schizophrenia. Anosognosia is associated with higher rates of noncompliance with treatment, a higher risk of repeated psychotic episodes, and a poorer prognosis for recovery.
• High rates of substance abuse disorders. About 50% of patients diagnosed with schizophrenia meet criteria for substance abuse or dependence. While substance abuse does not cause schizophrenia, it can worsen the symptoms of the disorder. Patients may have particularly bad reactions to amphetamines, cocaine, PCP (“angel dust”) or marijuana. It is thought that patients with schizophrenia are attracted to drugs of abuse as self-medication for some of their symptoms. The most common substance abused by patients with schizophrenia is tobacco; 90% of patients are heavy cigarette smokers, compared to 25-30% in the general adult population. Smoking is a serious problem for people with schizophrenia because it interferes with the effectiveness of their antipsychotic medications as well as increasing their risk of lung cancer and other respiratory diseases.
• High risk of suicide. About 40% of patients with schizophrenia attempt suicide at least once, and 10% eventually complete the act.
• High rates of obsessive-compulsive disorder and panic disorder.
• Downward drift. Downward drift is a sociological term that refers to having lower levels of educational achievement and/or employment than one’s parents.

VIOLENT BEHAVIOR

The connection between schizophrenia and personal assault or violence deserves mention because it is a major factor in the reactions of family members and the general public to the diagnosis. Researchers in both the United Kingdom and the United States have found that schizophrenia carries a heavier stigma than most other mental disorders, largely because of the mass media’s fascination with bizarre murders, dismemberment of animals, or other gruesome acts that are found to have been committed by a person with schizophrenia. Many patients report that the popular image of a schizophrenic as “a time bomb waiting to explode” is a source of considerable emotional stress.

Risk factors for violence in a patient diagnosed with schizophrenia include male sex, age below 30, prediagnosis history of violence, paranoid subtype, nonadherence to medication regimen, and heavy substance abuse. On the other hand, it should be noted that most crimes of violence are committed by people without a diagnosis of schizophrenia.

Demographics

In the United States, Canada, and Western Europe, the sex ratio in schizophrenia is 1.2:1, with males being affected slightly more often than females. There is a significant gender difference in average age at onset, however; the average for males is between ages 18 and 25, whereas for women there are two peaks, one between ages 25 and 35, and a second rise in incidence after age 45. About 15% of all women who develop schizophrenia are diagnosed after age 35. In some women, the first symptoms of the disorder appear postpartum (after giving birth). Many women with schizophrenia are initially misdiagnosed as having depression or bipolar disorder , because women with schizophrenia are likely to have more difficulties with emotional regulation than men with the disorder. In general, however, females have higher levels of functioning prior to symptom onset than males.

The incidence of schizophrenia in the United States appears to be uniform across racial and ethnic groups, with the exception of minority groups in urban neighborhoods in which they are a small proportion of the total population. A study done in the United Kingdom replicated American findings: There are significantly higher rates of schizophrenia among racial minorities living in large cities. The rates of schizophrenia are highest in areas in which these minority groups form the smallest proportion of the local population. The British study included Africans, West Indians of African descent, and Asians.

The incidence of schizophrenia in most developed countries appears to be higher among people born in cities than among those born in rural areas. In addition, there appears to be a small historical/generational factor, with the incidence of schizophrenia gradually declining in later-born groups.

Schizophrenia is a leading cause of disability, not only in the United States, but in other developed countries around the world. The World Health Organization (WHO) counts schizophrenia as in the world’s ten leading cause of disability. According to the National Institute of Mental Health (NIMH), 2.2 million American adults, or 1.1% of the population over age 18, suffer from schizophrenia. Other estimates run as high as 1.5% of the population.

Schizophrenia is disproportionately costly to society for reasons that go beyond the sheer number of people affected by the disorder. Although patients with schizophrenia are little more than 1% of the

population, they account for 2.5% of all health care costs. In the United States, patients with schizophrenia fill 25% of all hospital beds and account for about 20% of all Social Security disability days.

In addition, the onset of the disorder typically occurs during a young person’s last years of high school or their first years in college or the workforce; thus it often destroys their long-term plans for their future. According to the federal Agency for Healthcare Research and Quality, 70–80% of people diagnosed with schizophrenia are either unemployed or underemployed (working in jobs well below their actual capabilities). Ten percent of Americans with permanent disabilities have schizophrenia, as well as 20–30% of the homeless population.

Diagnosis

There are no symptoms that are unique to schizophrenia and no single symptom that is a diagnostic hallmark of the disorder. In addition, there are no laboratory tests or imaging studies that can establish or confirm a diagnosis of schizophrenia. The diagnosis is based on a constellation or group of related symptoms that are, according to DSM-IV-TR, “associated with impaired occupational or social functioning.”

As part of the process of diagnosis, the doctor will take a careful medical history and order laboratory tests of the patient’s blood or urine in order to rule out general medical conditions or substance abuse disorders that may be accompanied by disturbed behavior. X rays or other imaging studies of the head may also be ordered. Medical conditions to be ruled out include epilepsy, head trauma, brain tumor, Cushing’s syndrome, Wilson’s disease, Huntington’s disease, and encephalitis. Drugs of abuse that may cause symptoms resembling schizophrenia include amphetamines (“speed”), cocaine, and phencyclidine (PCP). In older patients, dementia and delirium must be ruled out. If the patient has held jobs involving exposure to mercury, polychlorinated biphenyls (PCBs), or other toxic substances, environmental poisoning must also be considered in the differential diagnosis.

The doctor must also rule out other mental disorders that may be accompanied by psychotic symptoms, such as mood disorders; brief psychotic disorders; dissociative disorder not otherwise specified or dissociative identity disorder ; delusional disorder; schizo-typal, schizoid, or paranoid personality disorders ; and pervasive developmental disorders . In children, childhood-onset schizophrenia must be distinguished from communication disorders with disorganized speech and from attention-deficit/hyperactivity disorder.

After other organic and mental disorders have been ruled out, it must be determined whether the patient meets the following criteria, as specified by DSM-IV-TR:

• Presence of positive and negative symptoms. The patient must have two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms.
• Decline in social, interpersonal, or occupational functioning, including personal hygiene or self-care.
• Duration. The symptomatic behavior must last for at least six months.

Treatments

Current treatment of schizophrenia focuses on symptom reduction and relapse prevention , since the causes of the disorder have not yet been clearly identified. Unfortunately, not all patients with schizophrenia receive adequate treatment. In addition, may schizophrenics do not take their medication because it does not adequately control their symptoms or produces adverse side effects.

Medications

Antipsychotic medications are the primary treatment for schizophrenia. Drug therapy for the disorder, however, is complicated by several factors: the unpredictability of a given patient’s response to specific medications, the number of potentially troublesome side effects, the high rate of substance abuse among patients with schizophrenia, and the possibility of drug interactions between antipsychotic medications and antidepressants or other medications that may be prescribed for the patient.

NEUROLEPTICS

The first antipsychotic medications for schizophrenia were introduced in the 1950s, and known as dopamine antagonists, or DAs. They are sometimes called neuroleptics, and include haloperidol (Haldol), chlorpromazine (Thorazine), per-phenazine (Trilafon), and fluphenazine (Prolixin). About 40% of patients, however, fail to respond to treatment with these medications. Neuroleptics can control most of the positive symptoms of schizophrenia as well as reduce the frequency and severity of relapses but they have little effect on negative symptoms. In addition, these medications have problematic side effects, ranging from dry mouth, blurry vision, and restlessness (akathisia) to such long-term side effects as tardive dyskinesia (TD). TD is a disorder characterized by involuntary movements of the mouth, lips, arms, or legs; it affects about 15-20% of

patients who have been receiving neuroleptic medications over a period of years. Discomfort related to these side effects is one reason why 40% of patients treated with the older antipsychotics do not adhere to their medication regimens.

ATYPICAL ANTIPSYCHOTICS

The atypical antipsychotics are newer medications introduced in the 1990s. They are sometimes called serotonin dopamine antagonists, or SDAs. These medications include aripiprazole (Abilify), clozapine (Clozaril), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geo-don), and olanzapine (Zyprexa). These newer drugs are more effective in treating the negative symptoms of schizophrenia and have fewer side effects than the older antipsychotics. Clozapine has been reported to be effective in patients who do not respond to neuro-leptics, and to reduce the risk of suicide attempts. The atypical antipsychotics, however, do have weight gain as a side effect; and patients taking clozapine must have their blood monitored periodically for signs of agranulocytosis, or a drop in the number of white blood cells.

Recently, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Study was a Phase IV clinical trial funded by the National Institute of Mental Health and coordinated by the University of North Carolina at Chapel Hill. The study investigated the effectiveness of several atypical antipsychotic drugs against that of a conventional drug. Contrary to expectations, however, it was found that the new drugs did not perform significantly better than the older drug. The results of the CATIE study also had implications to help schizophrenics and their physicians make decisions about which other drugs to try when one antipsychotic medication was unacceptable either because it did not adequately control symptoms or produced adverse side effects.

OTHER PRESCRIPTION MEDICATIONS

Patients with schizophrenia have a lifetime prevalence of 80% for major depression; others suffer from phobias or other anxiety disorders . The doctor may prescribe antide-pressants or a short course of benzodiazepines along with antipsychotic medications.

Inpatient treatment

Patients with schizophrenia are usually hospitalized during acute psychotic episodes, to prevent harm to themselves or to others, and to begin treatment with antipsychotic medications. A patient having a first psychotic episode is usually given a computed tomography (CT) or magnetic resonance imaging (MRI) scan to rule out structural brain disease.

Outpatient treatment

In recent years, patients with schizophrenia who have been stabilized on antipsychotic medications have been given psychosocial therapies of various types to assist them with motivation, self-care, and forming relationships with others. In addition, because many patients have had their education or vocational training interrupted by the onset of the disorder, they may be helped by therapies directed toward improving their social functioning and work skills.

Specific outpatient treatments that have been used with patients with schizophrenia include:

• Rehabilitation programs. These programs may offer vocational counseling, job training, problem-solving and money management skills, use of public transportation, and social skills training.
• Cognitive-behavioral therapy and supportive psychotherapy.
• Family psychoeducation. This approach is intended to help family members understand the patient’s illness, cope with the problems it creates for other family members, and minimize stresses that may increase the patient’s risk of relapse.
• Self-help groups. These groups provide mutual support for family members as well as patients. They can also serve as advocacy groups for better research and treatment, and to protest social stigma and employment discrimination.

Alternative and complementary therapies

Alternative and complementary therapies that are being investigated for the treatment of schizophrenia include gingko biloba, an Asian shrub, and vitamin therapy. One Chinese study reported that a group of patients who had not responded to conventional anti-psychotic medications benefited from a thirteen-week trial of gingko extract, with significantly fewer side effects. Vitamin therapy is recommended by naturo-pathic practitioners on the grounds that many hospitalized patients with schizophrenia suffer from nutritional deficiencies. The supplements recommended include folic acid, niacin, vitamin B6, and vitamin C.

Prognosis

The prognosis for patients diagnosed with schizophrenia varies. About 20% recover their previous level of functioning, while another 10% achieve significant and lasting improvement. About 30-35% show some improvement with intermittent relapses and some disabilities, while the remainder are severely and permanently incapacitated. Factors associated with a good prognosis include relatively good

KEY TERMS

Affect —The expression of emotion displayed to others through facial expressions, hand gestures, tone of voice, etc. Types of affect include: flat (inanimate, no expression), blunted (minimally responsive), inappropriate (incongruous expressions of emotion relative to the content of a conversation), and labile (sudden and abrupt changes in type and intensity of emotion).

Agranulocytosis —A blood disorder characterized by a reduction in the number of circulating white blood cells (granulocytes). White blood cells defend the body against infections. Agranulocytosis is a potential side effect of some of the newer antipsychotic medications used to treat schizophrenia.

Akathisia —Agitated or restless movement, usually affecting the legs. Movement is accompanied by a sense of discomfort and an inability to sit, stand still, or remain inactive for periods of time. Akathisia is a common side effect of some neuroleptic (antipsychotic) medications.

Anhedonia —Loss of the capacity to experience pleasure. Anhedonia is one of the so-called negative symptoms of schizophrenia, and is also a symptom of major depression.

Anosognosia —Lack of awareness of the nature of one’s illness. The term is usually applied to stroke patients, but is sometimes used to refer to lack of insight on the part of patients with schizophrenia. Anosognosia appears to be caused by the illness itself; it does not appear to be a form of denial or inappropriate coping mechanism. It is, however, a factor in nonadherence to treatment regimens and the increased risk of relapse.

Atypical antipsychotics —A group of newer medications for the treatment of psychotic symptoms that were introduced in the 1990s. The atypical antipsychotics include clozapine, risperidone, que-tiapine, ziprasidone, and olanzapine. They are sometimes called serotonin dopamine antagonists, or SDAs.

Blunted affect —A term that refers to the loss of emotional expressiveness sometimes found in patients with schizophrenia. It is sometimes called flattened affect.

Catatonia —Disturbance of motor behavior with either extreme stupor or random, purposeless activity.

Delusion —A false belief that is resistant to reason or contrary to actual fact. Common delusions in schizophrenia include delusions of persecution, delusions about one’s importance (sometimes called delusions of grandeur), or delusions of being controlled by others.

Dementia praecox —A late nineteenth-century term for schizophrenia.

Dopamine —A neurotransmitter that acts within certain brain cells to help regulate emotions and movement. Some of the symptoms of schizophrenia are related to excessive levels of dopamine activity in a part of the brain called the striatum.

Dystonia —A neurological disorder characterized by involuntary muscle spasms. The spasms can cause a painful twisting of the body and difficulty walking or moving.

First-rank symptoms —A list of symptoms that have been considered to be diagnostic of schizophrenia. They include delusions; somatic hallucinations; hearing voices commenting on one’s behavior; and thought insertion or withdrawal. First-rank symptoms are sometimes called Schneiderian symptoms, after the name of Kurt Schneider, the German psychiatrist who listed them in 1959.

functioning prior to the first psychotic episode; a late or sudden onset of illness; female sex; treatment with antipsychotic medications shortly after onset; good compliance with treatment; a family history of mood disorders rather than schizophrenia; minimal cognitive impairment; and a diagnosis of paranoid or non-deficit subtype. Factors associated with a poor prognosis include early age of onset; a low level of prior functioning; delayed treatment; heavy substance abuse; noncompliance with treatment; a family history of schizophrenia; and a diagnosis of disorganized or deficit subtype with many negative symptoms.

Prevention

The multifactorial and polygenic etiology (origins or causes) of schizophrenia complicates the search for preventive measures against the disorder. It is possible that the complete mapping of the human genome will identify a finite number of

Gingko biloba —A shade tree native to China with fan-shaped leaves and fleshy seeds with edible kernels. Gingko biloba extract is being studied as a possible complementary or adjunctive treatment for schizophrenia.

Hallucination —False sensory perceptions. A person experiencing a hallucination may “hear” sounds or “see” people or objects that are not really present. Hallucinations can also affect the senses of smell, touch, and taste.

Hebephrenic schizophrenia —An older term for what is now known as the disorganized subtype of schizophrenia.

Insidious —Proceeding gradually and inconspicuously but with serious effect. Schizophrenia sometimes has an insidious rather than an acute onset.

Morbidity —The unhealthiness or disease characteristics associated with a mental disorder.

Negative symptoms —Symptoms of schizophrenia that represent a loss or reduction of normal functioning.

Neuroleptic —Another name for the older antipsychotic medications, such as haloperidol (Haldol) and chlorpromazine (Thorazine).

Polygenic —A trait or disorder that is determined by a group of genes acting together. Most human characteristics, including height, weight, and general body build, are polygenic. Schizophrenia and late-onset Alzheimer’s disease are considered polygenic disorders.

Positive symptoms —Symptoms of schizophrenia that represent excesses or distortions of normal mental functions.

Prodromal —Premonitory; having the character of a warning. The first psychotic episode in schizophrenia is often preceded by a prodromal phase.

Psychosis —Severe state that is characterized by loss of contact with reality and deterioration in normal social functioning; examples are schizophrenia and paranoia. Psychosis is usually one feature of an over-arching disorder, not a disorder in itself. (Plural: psychoses)

Reality testing —A phrase that refers to a person’s ability to distinguish between subjective feelings and objective reality. A person who knows that their body is real even though they may be experiencing it as unreal, for example, is said to have intact reality testing.

Referential —A type of delusion in which the person misinterprets items, minor occurrences, or other people’s behavior as referring to them. Misinterpretations of this sort that are not as resistant to reality as a delusion are sometimes called ideas of reference.

Schneiderian symptoms —Another name for first-rank symptoms of schizophrenia.

Striatum —A part of the basal ganglia, a deep structure in the cerebral hemisphere of the brain. Abnormally high levels of dopamine in the striatum are thought to be related to the delusions and hallucinations of schizophrenia.

Supportive —An approach to psychotherapy that seeks to encourage the patient or offer emotional support to him or her, as distinct from insight-oriented or educational approaches to treatment.

Tardive dyskinesia —A condition that involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles that usually occurs either late in antipsychotic therapy or even after the therapy is discontinued. It may be irreversible.

Thought insertion/withdrawal —The notion that an outside force (space aliens, evil people, etc.) can put thoughts or ideas into one’s mind or remove them. It is considered one of the first-rank symptoms of schizophrenia.

genes that contribute to susceptibility to schizophrenia. The NIMH has presently compiled the world’s largest registry of families affected by schizophrenia in order to pinpoint specific genes for further study. The NIMH also sponsors a Prevention Research Initiative to identify points in the development of schizophrenia at which patients could benefit from the application of preventive efforts.

See alsoMedication-induced movement disorders.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text rev. Washington D.C.:American Psychiatric Association, 2000.

Kingdon, David G., and Douglas Turkington. Cognitive Therapy of Schizophrenia. New York: The Guilford Press, 2004.

Lieberman, Jeffrey A., T. Scott Stroup, and Diana O. Perkins, eds. The American Psychiatric Publishing

Textbook of Schizophrenia. Arlington, VA: American Psychiatric Publishing, 2006.

Marley, James A. Family Involvement in Treating Schizophrenia: Models, Essential Skills, and Process. Bing-hamton, NY: Haworth, 2003.

Shean, Glenn. Understanding and Treating Schizophrenia: Contemporary Research, Theory, and Practice. Bing-hamton, NY: Haworth Clinical Practice Press, 2004.

VandenBos, Gary R., ed. APA Dictionary of Psychology. Washington D.C.: American Psychological Association, 2007.

Williamson, Peter. Mind, Brain, and Schizophrenia. New York: Oxford University Press, 2005.

PERIODICALS

Barrowclough, Christine, and others. “Group Cognitive-Behavioural Therapy for Schizophrenia.” British Journal of Psychiatry 189.6 (Dec. 2006): 527–32.

Carr, Vaughan J., Terry J. Lewin, and Amanda L. Neil. “What Is the Value of Treating Schizophrenia?” Australian and New Zealand Journal of Psychiatry 40.11–12 (Nov. 2006): 963–71.

Gray, Richard, et al. “Adherence Therapy for People with Schizophrenia.” British Journal of Psychiatry 189.6 (Dec. 2006): 508–14.

Lawrence, R., T. Bradshaw, and H. Mairs. “Group Cognitive Behavioural Therapy for Schizophrenia: A Systematic Review of the Literature.” Journal of Psychiatric and Mental Health Nursing 13.6 (Dec. 2006): 673–81.

Lipkovich, I., et al. “Predictors of Risk for Relapse in Patients With Schizophrenia or Schizoaffective Disorder During Olanzapine Drug Therapy.” Journal of Psychiatric Research 41.3–4 (Apr.–Jun. 2007): 305–10.

Masand, Prakash S., et al. “Polypharmacy in Schizophrenia.” International Journal of Psychiatry in Clinical Practice 10.4 (Dec. 2006): 258–63.

Yanos, P. T., and R. H. Moos. “Determinants of Functioning and Well-Being Among Individuals With Schizophrenia: An Integrated Model.” Clinical Psychology Review 27.1 (Jan. 2007): 58–77.

ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry. 3615 Wisconsin Avenue, NW, Washington, DC 20016-3007. Telephone: (202) 966-7300. Fax: (202) 966-2891. www.aacap.org

The National Alliance for the Mentally Ill (NAMI). 200 North Glebe Road, Suite 1015, Arlington, VA 22203-3754. Telephone: (800) 950-NAMI or (703) 524-7600. www.nami.org

National Alliance for Research on Schizophrenia and Depression (NARSAD). 60 Cutter Mill Road, Suite 404, Great Neck, NY 11021. Telephone: (516) 829-0091. www.mhsource.com

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. Telephone: (301) 443-4513. www.nimh.nih.gov

National Mental Health Association (NMHA). 1021 Prince Street, Alexandria, VA 22314-2971. Telephone: (800) 969-6942 or (703) 684-7722. www.nmha.org

OTHER

National Institute of Mental Health (NIMH). The Numbers Count. NIH Publication No. 01-4584 (2000). www.nimh.nih.gov/publicat/numbers.cfm

National Institutes of Health (NIH). News Release, January 28, 2002. “Scans Link 2 Key Pieces of Schizophrenia Puzzle.” www.nih.gov/news/pr/jan2002/nimh-28.htm

Rebecca Frey, PhD Ruth A. Wienclaw, PhD

Schizophrenia

Definition

Schizophrenia is the most chronic and disabling of the severe mental disorders, associated with abnormalities of brain structure and function, disorganized speech and behavior, delusions , and hallucinations . It is sometimes called a psychotic disorder or a psychosis .

Description

People diagnosed with schizophrenia do not always have the same set of symptoms; in addition, a given patient's symptoms may change over time. Since the nineteenth century, doctors have recognized different subtypes of the disorder, but no single classification system has gained universal acceptance. Some psychiatrists prefer to speak of schizophrenia as a group or family of disorders ("the schizophrenias") rather than as a single entity. A standard professional reference, The Diagnostic and Statistical Manual of Mental Disorders (also known as the DSM-IV-TR) acknowledges that its present classification of subtypes is not fully satisfactory for either clinical or research purposes, and states that "alternative subtyping schemes are being actively investigated."

The symptoms of schizophrenia can appear at any time after age six or seven, although onset during adolescence and early adult life is the most common pattern. There are a few case studies in the medical literature of schizophrenia in children younger than five, but they are extremely rare. Schizophrenia that appears after age 45 is considered late-onset schizophrenia. About 1%–2% of cases are diagnosed in patients over 80.

The onset of symptoms in schizophrenia may be either abrupt (sudden) or insidious (gradual). Often, however, it goes undetected for about two to three years after the onset of diagnosable symptoms, because the symptoms occur in the context of a previous history of cognitive and behavioral problems. The patient may have had panic attacks, social phobia , or substance abuse problems, any of which can complicate the process of diagnosis . In most cases, however, the patient's first psychotic episode is preceded by a prodromal (warning) phase, with a variety of behaviors that may include angry outbursts, withdrawal from social activities, loss of attention to personal hygiene and grooming, anhedonia (loss of one's capacity for enjoyment), and other unusual behaviors. The psychotic episode itself is typically characterized by delusions, which are false but strongly held beliefs that result from the patient's inability to separate real from unreal events; and hallucinations, which are disturbances of sense perception. Hallucinations can affect any of the senses, although the most common form of hallucination in schizophrenia is auditory ("hearing voices"). Autobiographical accounts by people who have recovered from schizophrenia indicate that these hallucinations are experienced as frightening and confusing. Patients often find it difficult to concentrate on work, studies, or formerly pleasurable activities because of the constant "static" or "buzz" of hallucinated voices.

There is no "typical" pattern or course of the disorder following the first acute episode. The patient may never have a second psychotic episode; others have occasional episodes over the course of their lives but can lead fairly normal lives otherwise. About 70% of patients diagnosed with schizophrenia have a second psychotic breakdown within five to seven years after the first one.

Some patients remain chronically ill; of these, some remain at a fairly stable level while others grow steadily worse and become severely disabled.

About 20% of patients with schizophrenia recover the full level of functioning that they had before the onset of the disorder, according to NIMH statistics; but the remaining 80% have problems reintegrating into mainstream society. These patients are often underachievers in school and in the workplace, and they usually have difficulty forming healthy relationships with others. The majority (60%–70%) of patients with schizophrenia do not marry or have children, and most have very few friends or social contacts. The impact of these social difficulties as well as the stress caused by the symptoms themselves is reflected in the high suicide rate among patients with schizophrenia. About 10% commit suicide within the first 10 years after their diagnosis— a rate 20 times higher than that of the general population.

Subtypes of schizophrenia

DSM-IV-TR specifies five subtypes of schizophrenia:

• Paranoid type. The central feature of this subtype is the presence of auditory hallucinations or delusions alongside relatively unaffected mood and cognitive functions. The patient's delusions usually involve persecution, grandiosity, or both. About a third of patients diagnosed with schizophrenia in the United States belong to this subtype.
• Disorganized type. The core features of this subtype include disorganized speech, disorganized behavior, and flat or inappropriate affect. The person may lose the ability to perform most activities of daily living, and may also make faces or display other oddities of behavior. This type of schizophrenia was formerly called hebephrenic (derived from the Greek word for puberty), because some of the patients' behaviors resemble adolescent silliness.
• Catatonic type. Catatonia refers to disturbances of movement, whether remaining motionless for long periods of time or excessive and purposeless movement. The absence of movement may take the form of catalepsy, which is a condition in which the patient's body has a kind of waxy flexibility and can be repositioned by others; or negativism, a form of postural rigidity in which the patient resists being moved by others. A catatonic patient may assume bizarre postures or imitate the movements of other people.
• Undifferentiated type. Patients in this subtype have some of the characteristic symptoms of schizophrenia but do not meet the full criteria for the paranoid, disorganized, or catatonic subtypes.
• Residual type. Patients in this category have had at least one psychotic episode, continue to have some negative symptoms of schizophrenia, but do not have current psychotic symptoms.

Cultural variables

There appear to be some differences across cultures in the symptoms associated with schizophrenia. The catatonic subtype appears to be more common in non-Western countries than in Europe or North America. Other studies indicate that persons diagnosed with schizophrenia in developing countries have a more acute onset of the disorder but better outcomes than patients in the developed countries.

Causes and symptoms

Causes

As of 2002, schizophrenia is considered the end result of a combination of genetic, biochemical, developmental, and environmental factors, some of which are still not completely understood. There is no known single cause of the disorder.

GENETIC. Researchers have known for many years that first-degree biological relatives of patients with schizophrenia have a 10% risk of developing the disorder, as compared with 1% in the general population. The monozygotic (identical) twin of a person with schizophrenia has a 40%–50% risk. The fact that this risk is not higher, however, indicates that environmental as well as genetic factors are implicated in the development of schizophrenia.

Some specific regions on certain human chromosomes have been linked to schizophrenia. In late 2001, a multidisciplinary team of researchers reported positive associations for schizophrenia on chromosomes 15 and 13. Chromosome 15 is linked to schizophrenia in European-American families as well as some Taiwanese and Portuguese families. A recent study of the biological pedigrees found among the inhabitants of Palau (an isolated territory in Micronesia) points to chromosomes 2 and 13. Still another team of researchers has suggested that a disorder known as 22q deletion syndrome may actually represent a subtype of schizophrenia, insofar as people with this syndrome have a 25% risk of developing schizophrenia. At present scientists are inclined to think that the genetic factors underlying schizophrenia vary across different ethnic groups, so that it is highly unlikely that susceptibility to the disorder is determined by only one gene. As of 2002, schizophrenia is considered a polygenic disorder.

There appears to be a connection between aging and genetic mutations that increases susceptibility to schizophrenia. A recent Israeli study found that the age of a person's father is a risk factor for schizophrenia; the older the father, the higher the rate of mutations in sperm cells. The child of a father older than 50 is three times more likely to develop schizophrenia than children born to younger men. The researchers suggest that mutations in the sperm cells of older men help to explain why schizophrenia has persisted in the human population even though few schizophrenics marry and have children.

DEVELOPMENTAL. As of 2002, there is some evidence that schizophrenia may be a type of developmental disorder related to the formation of faulty connections between nerve cells during fetal development. The changes in the brain that normally occur during puberty then interact with these connections to trigger the symptoms of the disorder. Other researchers have suggested that a difficult childbirth may result in developmental vulnerabilities that eventually lead to schizophrenia.

NEUROBIOLOGICAL. In early 2002, researchers at the NIMH demonstrated the existence of a connection between two abnormalities of brain functioning in patients with schizophrenia. The researchers used radioactive tracers and positron emission tomography (PET) to show that reduced activity in a part of the brain called the prefrontal cortex was associated in the patients, but not in the control subjects, with abnormally elevated levels of dopamine in the striatum. High levels of dopamine are related to the delusions and hallucinations of psychotic episodes in schizophrenia. The findings suggest that treatment directed at the prefrontal cortex might be more effective than present antipsychotic medications, which essentially target dopamine levels without regard to specific areas of the brain.

Another area of investigation concerns abnormalities in brain structure that are found in some patients with schizophrenia. One of these abnormalities is the increased size of the ventricles, which are cavities in the interior of the brain filled with cerebrospinal fluid. Another is a decrease in size of some areas of the brain. A California study of MRI scans of teenagers with early-onset schizophrenia found that they lost over 10% of the gray matter of the brain over the course of five years. The frontal eye fields showed the most rapid rate of tissue loss—about 5% per year. A major difficulty in interpreting these findings is that these abnormalities are not found in the brains of all patients with schizophrenia. In addition, they sometimes occur in the brains of people who do not have the disorder.

ENVIRONMENTAL. Certain environmental factors during pregnancy are associated with an increased risk of schizophrenia in the offspring. These include the mother's exposure to starvation or famine; influenza during the second trimester of pregnancy; and Rh incompatibility in a second or third pregnancy.

Some researchers are investigating a possible connection between schizophrenia and viral infections of the hippocampus, a structure in the brain that is associated with memory formation and the human stress response. It is thought that damage to the hippocampus might account for the sensory disturbances found in schizophrenia. Another line of research related to viral causes of schizophrenia concerns a protein deficiency in the brain. Researchers at the University of Kiel in Germany think that the deficiency is the result of viral infections.

Environmental stressors related to home and family life (parental death or divorce, family dysfunction) or to separation from the family of origin in late adolescence (going away to college or military training; marriage) may trigger the onset of schizophrenia in individuals with genetic or psychological vulnerabilities.

Symptoms

The symptoms of schizophrenia are divided into two major categories: positive symptoms , which are defined by DSM-IV-TR as excesses or distortions of normal mental functions; and negative symptoms , which represent a loss or reduction of normal functioning. Of the two types, the negative symptoms are more difficult to evaluate because they may be influenced by a concurrent depression or a dull and unstimulating environment, but they account for much of the morbidity (unhealthiness) associated with schizophrenia.

POSITIVE SYMPTOMS. The positive symptoms of schizophrenia include four so-called "first-rank" or Schneiderian symptoms, named for a German psychiatrist who identified them in 1959:

• Delusions. A delusion is a false belief that is resistant to reason or to confrontation with actual facts. The most common form of delusion in patients with schizophrenia is persecutory; the person believes that others— family members, clinical staff, terrorists, etc.—are "out to get" them. Another common delusion is referential, which means that the person interprets objects or occurrences in the environment (a picture on the wall, a song played on the radio, laughter in the corridor, etc.) as being directed at or referring to them.
• Somatic hallucinations. Somatic hallucinations refer to sensations or perceptions about one's body organs that have no known medical cause, such as feeling that snakes are crawling around in one's intestines or that one's eyes are emitting radioactive rays.
• Hearing voices commenting on one's behavior or talking to each other. Auditory hallucinations are the most common form of hallucination in schizophrenia, although visual, tactile, olfactory, and gustatory hallucinations may also occur. Personal accounts of recovery from schizophrenia often mention "the voices" as one of the most frightening aspects of the disorder.
• Thought insertion or withdrawal. These terms refer to the notion that other beings or forces (God, aliens from outer space, the CIA, etc.) can put thoughts or ideas into one's mind or remove them.

Other positive symptoms of schizophrenia include:

• Disorganized speech and thinking. A person with schizophrenia may ramble from one topic to another (derailment or loose associations); may give unrelated answers to questions (tangentiality); or may say things that cannot be understood because there is no grammatical structure to the language ("word salad" or incoherence).
• Disorganized behavior. This symptom includes such behaviors as agitation; age-inappropriate silliness; inability to maintain personal hygiene; dressing inappropriately for the weather; sexual self-stimulation in public; shouting at people, etc. In one case study, the patient played his flute for hours on end while standing on top of the family car.
• Catatonic behavior. Catatonic behaviors have been described with regard to the catatonic subtype of schizophrenia. This particular symptom is sometimes found in other mental disorders.

NEGATIVE SYMPTOMS. The negative symptoms of schizophrenia include:

• Blunted or flattened affect. This term refers to loss of emotional expressiveness. The person's face may be unresponsive or expressionless, and speech may lack vitality or warmth.
• Alogia. Alogia is sometimes called poverty of speech. The person has little to say and is not able to expand on their statements. A doctor examining the patient must be able to distinguish between alogia and unwillingness to speak.
• Avolition. The person is unable to begin or stay with goal-directed activities. They may sit in one location for long periods of time or show little interest in joining group activities.
• Anhedonia. Anhedonia refers to the loss of one's capacity for enjoyment or pleasure.

OTHER SYMPTOMS AND CHARACTERISTICS. Although the following symptoms and features are not diagnostic criteria of schizophrenia, most patients with the disorder have one or more:

• Dissociative symptoms, particularly depersonalization and derealization.
• Anosognosia. This term originally referred to the inability of stroke patients to recognize their physical disabilities, but is sometimes used to refer to lack of insight in patients with schizophrenia. Anosognosia is associated with higher rates of noncompliance with treatment, a higher risk of repeated psychotic episodes, and a poorer prognosis for recovery.
• High rates of substance abuse disorders. About 50% of patients diagnosed with schizophrenia meet criteria for substance abuse or dependence. While substance abuse does not cause schizophrenia, it can worsen the symptoms of the disorder. Patients may have particularly bad reactions to amphetamines , cocaine, PCP ("angel dust") or marijuana. It is thought that patients with schizophrenia are attracted to drugs of abuse as self-medication for some of their symptoms. The most common substance abused by patients with schizophrenia is tobacco; 90% of patients are heavy cigarette smokers, compared to 25%–30% in the general adult population. Smoking is a serious problem for people with schizophrenia because it interferes with the effectiveness of their antipsychotic medications as well as increasing their risk of lung cancer and other respiratory diseases.
• High risk of suicide . About 40% of patients with schizophrenia attempt suicide at least once, and 10% eventually complete the act.
• High rates of obsessive-compulsive disorder and panic disorder.
• Downward drift. Downward drift is a sociological term that refers to having lower levels of educational achievement and/or employment than one's parents.

VIOLENT BEHAVIOR. The connection between schizophrenia and personal assault or violence deserves mention because it is a major factor in the reactions of family members and the general public to the diagnosis. Researchers in both the United Kingdom and the United States have found that schizophrenia carries a heavier stigma than most other mental disorders, largely because of the mass media's fascination with bizarre murders, dismemberment of animals, or other gruesome acts committed by people with schizophrenia. Many patients report that the popular image of a schizophrenic as "a time bomb waiting to explode" is a source of considerable emotional stress.

Risk factors for violence in a patient diagnosed with schizophrenia include male sex, age below 30, prediagnosis history of violence, paranoid subtype, nonadherence to medication regimen, and heavy substance abuse. On the other hand, it should be noted that most crimes of violence are committed by people without a diagnosis of schizophrenia. In addition, a study of patients with schizophrenia living in the community found that "... individuals in this sample were at least 14 times more likely to be victims of a violent crime than to be arrested for one."

Demographics

In the United States, Canada, and Western Europe, the sex ratio in schizophrenia is 1.2:1, with males being affected slightly more often than females. There is a significant gender difference in average age at onset, however; the average for males is between ages 18 and 25, whereas for women there are two peaks, one between ages 25 and 35, and a second rise in incidence after age 45. About 15% of all women who develop schizophrenia are diagnosed after age 35. In some women, the first symptoms of the disorder appear postpartum (after giving birth). Many women with schizophrenia are initially misdiagnosed as having depression or bipolar disorder , because women with schizophrenia are likely to have more difficulties with emotional regulation than men with the disorder. In general, however, females have higher levels of functioning prior to symptom onset than males.

The incidence of schizophrenia in the United States appears to be uniform across racial and ethnic groups, with the exception of minority groups in urban neighborhoods in which they are a small proportion of the total population. A recent study done in the United Kingdom replicated American findings: there are significantly higher rates of schizophrenia among racial minorities living in large cities. The rates of schizophrenia are highest in areas in which these minority groups form the smallest proportion of the local population. The British study included Africans, Caribbeans of African descent, and Asians.

The incidence of schizophrenia in most developed countries appears to be higher among people born in cities than among those born in rural areas. In addition, there appears to be a small historical/generational factor, with the incidence of schizophrenia gradually declining in later-born groups.

Schizophrenia is a leading cause of disability, not only in the United States, but in other developed countries around the world. In 1997, the World Health Organization (WHO) listed schizophrenia as the world's ninth leading cause of disability. According to the National Institute of Mental Health (NIMH), 2.2 million American adults, or 1.1% of the population over age 18, suffer from schizophrenia. Other estimates run as high as 1.5% of the population.

Schizophrenia is disproportionately costly to society for reasons that go beyond the sheer number of people affected by the disorder. Although patients with schizophrenia are little more than 1% of the population, they account for 2.5% of all health care costs—$40 billion per year in the United States, $2.35 billion in Canada (in Canadian dollars), and 2.6 billion pounds sterling (about $7.28 billion in US dollars) in Great Britain. In the United States, patients with schizophrenia fill 25% of all hospital beds and account for about 20% of all Social Security disability days.

In addition, the onset of the disorder typically occurs during a young person's last years of high school or their first years in college or the workforce; thus it often destroys their long-term plans for their future. According to the federal Agency for Healthcare Research and Quality, 70%–80% of people diagnosed with schizophrenia are either unemployed or underemployed (working in jobs well below their actual capabilities). Ten percent of Americans with permanent disabilities have schizophrenia, as well as 20%–30% of the homeless population.

Diagnosis

There are no symptoms that are unique to schizophrenia and no single symptom that is a diagnostic hallmark of the disorder. In addition, as of 2002 there are no laboratory tests or imaging studies that can establish or confirm a diagnosis of schizophrenia. The diagnosis is based on a constellation or group of related symptoms that are, according to DSM-IV-TR, "associated with impaired occupational or social functioning."

As part of the process of diagnosis, the doctor will take a careful medical history and order laboratory tests of the patient's blood or urine in order to rule out general medical conditions or substance abuse disorders that may be accompanied by disturbed behavior. X rays or other imaging studies of the head may also be ordered. Medical conditions to be ruled out include epilepsy, head trauma, brain tumor, Cushing's syndrome, Wilson's disease, Huntington's disease, and encephalitis. Drugs of abuse that may cause symptoms resembling schizophrenia include amphetamines ("speed"), cocaine, and phencyclidine (PCP). In older patients, dementia and delirium must be ruled out. If the patient has held jobs involving exposure to mercury, polychlorinated biphenyls (PCBs), or other toxic substances, environmental poisoning must also be considered in the differential diagnosis.

The doctor must then rule out other mental disorders that may be accompanied by psychotic symptoms, such as mood disorders; brief psychotic disorders; dissociative disorder not otherwise specified or dissociative identity disorder ; delusional disorder ; schizotypal, schizoid, or paranoid personality disorders ; and pervasive developmental disorders . In children, childhood-onset schizophrenia must be distinguished from communication disorders with disorganized speech and from attention-deficit/hyperactivity disorder .

After the doctor has ruled out other organic and mental disorders, he or she must then determine whether the patient meets the following criteria, as specified by DSM-IV-TR :

• Presence of positive and negative symptoms. The patient must have two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms.
• Decline in social, interpersonal, or occupational functioning, including personal hygiene or self-care.
• Duration. The symptomatic behavior must last for at least six months.

Treatments

Current treatment of schizophrenia focuses on symptom reduction and relapse prevention, since the causes of the disorder have not yet been clearly identified. Unfortunately, not all patients with schizophrenia receive adequate treatment. In 2000, the NIMH released the results of a large-scale community study, which indicated that fewer than half of patients with schizophrenia receive correct dosages of their medications or adequate psychosocial treatment.

Medications

Medications are the mainstay of treatment for schizophrenia. Drug therapy for the disorder, however, is complicated by several factors: the unpredictability of a given patient's response to specific medications, the number of potentially troublesome side effects, the high rate of substance abuse among patients with schizophrenia, and the possibility of drug interactions between antipsychotic medications and antidepressants or other medications that may be prescribed for the patient.

NEUROLEPTICS. The first antipsychotic medications for schizophrenia were introduced in the 1950s, and known as dopamine antagonists, or DAs. They are sometimes called neuroleptics, and include haloperidol (Haldol), chlorpromazine (Thorazine), perphenazine (Trilafon), and fluphenazine (Prolixin). About 40% of patients, however, fail to respond to treatment with these medications. Neuroleptics can control most of the positive symptoms of schizophrenia as well as reduce the frequency and severity of relapses but they have little effect on negative symptoms. In addition, these medications have problematic side effects, ranging from dry mouth, blurry vision, and restlessness (akathisia) to such long-term side effects as tardive dyskinesia (TD). TD is a disorder characterized by involuntary movements of the mouth, lips, arms, or legs; it affects about 15%–20% of patients who have been receiving neuroleptic medications over a period of years. Discomfort related to these side effects is one reason why 40% of patients treated with the older antipsychotics do not adhere to their medication regimens.

ATYPICAL ANTIPSYCHOTICS. The atypical antipsychotics are newer medications introduced in the 1990s. They are sometimes called serotonin dopamine antagonists, or SDAs. These medications include clozapine (Clozaril), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa). These newer drugs are more effective in treating the negative symptoms of schizophrenia and have fewer side effects than the older antipsychotics. Clozapine has been reported to be effective in patients who do not respond to neuroleptics, and to reduce the risk of suicide attempts. The atypical antipsychotics, however, do have weight gain as a side effect; and patients taking clozapine must have their blood monitored periodically for signs of agranulocytosis, or a drop in the number of white blood cells. These drugs are now considered first-line treatments for patients having their first psychotic episode.

OTHER PRESCRIPTION MEDICATIONS. Patients with schizophrenia have a lifetime prevalence of 80% for major depression; others suffer from phobias or other anxiety disorders. The doctor may prescribe antidepressants or a short course of benzodiazepines along with antipsychotic medications.

Inpatient treatment

Patients with schizophrenia are usually hospitalized during acute psychotic episodes, to prevent harm to themselves or to others, and to begin treatment with antipsychotic medications. A patient having a first psychotic episode is usually given a computed tomography (CT) or magnetic resonance imaging (MRI) scan to rule out structural brain disease.

Outpatient treatment

In recent years, patients with schizophrenia who have been stabilized on antipsychotic medications have been given psychosocial therapies of various types to assist them with motivation, self-care, and forming relationships with others. In addition, because many patients have had their education or vocational training interrupted by the onset of the disorder, they may be helped by therapies directed toward improving their social functioning and work skills.

Specific outpatient treatments that have been used with patients with schizophrenia include:

• Rehabilitation programs. These programs may offer vocational counseling, job training, problem-solving and money management skills, use of public transportation, and social skills training .
• Cognitive-behavioral therapy and supportive psychotherapy .
• Family psychoeducation . This approach is intended to help family members understand the patient's illness, cope with the problems it creates for other family members, and minimize stresses that may increase the patient's risk of relapse.
• Self-help groups . These groups provide mutual support for family members as well as patients. They can also serve as advocacy groups for better research and treatment, and to protest social stigma and employment discrimination.

Alternative and complementary therapies

Alternative and complementary therapies that are being investigated for the treatment of schizophrenia include gingko biloba , an Asian shrub, and vitamin therapy. One Chinese study reported that a group of patients who had not responded to conventional antipsychotic medications benefited from a thirteen-week trial of gingko extract, with significantly fewer side effects. Vitamin therapy is recommended by naturopathic practitioners on the grounds that many hospitalized patients with schizophrenia suffer from nutritional deficiencies. The supplements recommended include folic acid, niacin, vitamin B₆, and vitamin C.

Prognosis

The prognosis for patients diagnosed with schizophrenia varies. About 20% recover their previous level of functioning, while another 10% achieve significant and lasting improvement. About 30%–35% show some improvement with intermittent relapses and some disabilities, while the remainder are severely and permanently incapacitated. Factors associated with a good prognosis include relatively good functioning prior to the first psychotic episode; a late or sudden onset of illness; female sex; treatment with antipsychotic medications shortly after onset; good compliance with treatment; a family history of mood disorders rather than schizophrenia; minimal cognitive impairment; and a diagnosis of paranoid or nondeficit subtype. Factors associated with a poor prognosis include early age of onset; a low level of prior functioning; delayed treatment; heavy substance abuse; noncompliance with treatment; a family history of schizophrenia; and a diagnosis of disorganized or deficit subtype with many negative symptoms.

Prevention

The multifactorial and polygenic etiology (origins or causes) of schizophrenia complicates the search for preventive measures against the disorder. It is possible that the complete mapping of the human genome will identify a finite number of genes that contribute to susceptibility to schizophrenia. The NIMH has presently compiled the world's largest registry of families affected by schizophrenia in order to pinpoint specific genes for further study. The NIMH also sponsors a Prevention Research Initiative to identify points in the development of schizophrenia at which patients could benefit from the application of preventive efforts.

See also Medication-induced movement disorders

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edition, text revised. Washington, DC: American Psychiatric Association,2000.

Friedrich, Otto. Going Crazy: An Inquiry Into Madness in Our Time. New York: Avon Books, 1977.

Martin, John H., PhD. Neuroanatomy: Text and Atlas. Second edition. Norwalk, CT: Appleton and Lange, 1996.

North, Carol S., MD. Welcome Silence: My Triumph Over Schizophrenia. New York: Simon and Schuster, Inc.,1989.

Pelletier, Kenneth R., MD. "CAM Therapies for Specific Conditions: Schizophrenia." In The Best Alternative Medicine, Part II. New York: Simon and Schuster, 2002.

"Schizophrenia and Related Disorders." Section 15, Chapter 193 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2001.

Wahl, Otto F. Telling Is Risky Business: Mental Health Consumers Confront Stigma. New Brunswick, NJ: Rutgers University Press, 1999.

PERIODICALS

AACAP Council. "Practice Parameter for the Assessment and Treatment of Children and Adolescents with Schizophrenia." Journal of the American Academy of Child and Adolescent Psychiatry 40 (July 2001 Supplement): 4S–23S.

Barrowclough, Christine, Gillian Haddock, Nicholas Tarrier, and others. "Randomized Controlled Trial of Motivational Interviewing, Cognitive Behavior Therapy, and Family Intervention for Patients with Comorbid Schizophrenia and Substance Use Disorders." American Journal of Psychiatry 158 (October 2001): 1706–1713.

Bassett, A. S., S. O'Neill, J. Murphy, and others. "Expression of Schizophrenic Symptoms in 22q Deletion Syndrome." American Journal of Human Genetics 69 (October2001): 287.

Bower, Bruce. "Back from the Brink (Therapies for Schizophrenia)." Science News 159 (April 28, 2001): 268.

Boydell, J., J. van Os, K. McKenzie, and others. "Incidence of Schizophrenia in Ethnic Minorities in London: Ecological Study Into Interactions With the Environment." British Medical Journal 323 (December 8, 2001): 1336–1338.

Brekke, John S. "Risks for Individuals with Schizophrenia Who Are Living in the Community." Journal of the American Medical Association 286 (December 19, 2001): 2922.

Camp, Nicola J., Susan L. Neuhausen, Josepha Tiobech, and others. "Genomewide Multipoint Linkage Analysis of Seven Extended Palauan Pedigrees with Schizophrenia, by a Markov-Chain Monte Carlo Method." American Journal of Human Genetics 69 (December 2001): 1278–1289.

"Consider Clozapine for Reducing Suicide Risk in Schizophrenia." Clinical Psychiatry News 29 (November2001): 22.

Cormac, I., C. Jones, C. Campbell. "Cognitive Behaviour Therapy for Schizophrenia (Cochrane Review)." Cochrane Database Systems Review (2002): CD000524.

Fisher, Daniel B. "Recovering from Schizophrenia." (Guest Editorial). Clinical Psychiatry News 29 (November 2001): 30.

Frangou, Sophia. "How to Manage the First Episode of Schizophrenia: Early Diagnosis and Treatment May Prevent Social Disability Later." British Medical Journal 321 (September 2, 2000): 522.

Jancin, Bruce. "Women Often Defy Schizophrenia's Classic Course." Clinical Psychiatry News 29 (October 2001): 30.

Lehman, A. F., R. Goldberg, L. B. Dixon, and others. "Improving Employment Outcomes for Persons with Severe Mental Illness." Archives of General Psychiatry 59 (February 2002): 165–172.

McGrath, John. "Treatment of Schizophrenia." British Medical Journal 319 (October 16, 1999): 1045–1083.

"MRI Reveals Brain Changes Associated with Schizophrenia." Mental Health Weekly 11 (October 1,2001): 8.

Myin-Germeys I., L. Krabbendam, J. Jolles, and others. "Are Cognitive Impairments Associated with Sensitivity to Stress in Schizophrenia? An Experience Sampling Study." American Journal of Psychiatry 159 (March 2002): 443–449.

Nakaya, M., K. Kusumoto, K. Ohmori. "Subjective Experiences of Japanese Inpatients with Chronic Schizophrenia." Journal of Nervous and Mental Disorders 190 (February 2002): 80–85.

"Old Fathers and Schizophrenia." Harvard Mental Health Letter 18 (October 2001).

Ross, Brendan. "Novel Antipsychotic Drugs in the Management of Schizophrenia." Drug Topics (May 7,2001): 72–84.

"Schizophrenia May Be Linked to Brain Protein Deficiency." Mental Health Weekly 11 (November 19, 2001): 7.

Swofford, Cheryl D. "Double Jeopardy: Schizophrenia and Substance Abuse." American Journal of Drug and Alcohol Abuse 26 (August 2000): 343.

Weiser, Mark, Avraham Reichenberg, Jonathan Rabinowitz, and others. "Association Between Nonpsychotic Psychiatric Diagnoses in Adolescent Males and Subsequent Onset of Schizophrenia." Archives of General Psychiatry 58 (October 2001): 959–964.

Werbach, Melvyn R. "Vitamins for Treating Schizophrenia." Townsend Letter for Doctors and Patients (April 2001): 55–60.

ORGANIZATIONS

American Academy of Child and Adolescent Psychiatry. 3615 Wisconsin Avenue, NW, Washington, DC 20016-3007.(202) 966-7300. Fax: (202) 966-2891. <www.aacap.org>.

The National Alliance for the Mentally Ill (NAMI). 200 North Glebe Road, Suite 1015, Arlington, VA 22203-3754.(800) 950-NAMI or (703) 524-7600. <www.nami.org>.

National Alliance for Research on Schizophrenia and Depression (NARSAD). 60 Cutter Mill Road, Suite 404, Great Neck, NY 11021. (516) 829-0091. <www.mhsource.com>.

National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. <www.nimh.nih.gov>.

National Mental Health Association (NMHA). 1021 Prince Street, Alexandria, VA 22314-2971. (800) 969-6942 or(703) 684-7722. <www.nmha.org>.

OTHER

National Institute of Mental Health (NIMH). The Numbers Count. NIH Publication No. 01-4584 (2000). <www.nimh.nih.gov/publicat/numbers.cfm>.

National Institutes of Health (NIH). News Release, January 28, 2002. "Scans Link 2 Key Pieces of Schizophrenia Puzzle." <www.nih.gov/news/pr/jan2002/nimh-28.htm>.

Rebecca J. Frey, Ph.D.

Schizophrenia

Definition

Schizophrenia is a psychotic disorder (or a group of disorders) marked by severely impaired thinking, emotions, and behaviors. Schizophrenic patients are typically unable to filter sensory stimuli and may have enhanced perceptions of sounds, colors, and other features of their environment. Most schizophrenics, if untreated, gradually withdraw from interactions with other people, and lose their ability to take care of personal needs and grooming.

The prevalence of schizophrenia is thought to be about 1% of the population around the world; it is thus more common than diabetes, Alzheimer's disease, or multiple sclerosis. In the United States and Canada, patients with schizophrenia fill about 25% of all hospital beds. The disorder is considered to be one of the top ten causes of long-term disability worldwide.

Description

The course of schizophrenia in adults can be divided into three phases or stages. In the acute phase, the patient has an overt loss of contact with reality (psychotic episode) that requires intervention and treatment. In the second or stabilization phase, the initial psychotic symptoms have been brought under control but the patient is at risk for relapse if treatment is interrupted. In the third or maintenance phase, the patient is relatively stable and can be kept indefinitely on antipsychotic medications. Even in the maintenance phase, however, relapses are not unusual and patients do not always return to full functioning.

The English term schizophrenia comes from two Greek words that mean "split mind." It was observed around 1908, by a Swiss doctor named Eugen Bleuler, to describe the splitting apart of mental functions that he regarded as the central characteristic of schizophrenia.

Recently, some psychotherapists have begun to use a classification of schizophrenia based on two main types. People with Type I, or positive schizophrenia, have a rapid (acute) onset of symptoms and tend to respond well to drugs. They also tend to suffer more from the "positive" symptoms, such as delusions and hallucinations. People with Type II, or negative schizophrenia, are usually described as poorly adjusted before their schizophrenia slowly overtakes them. They have predominantly "negative" symptoms, such as withdrawal from others and a slowing of mental and physical reactions (psychomotor retardation).

There are five subtypes of schizophrenia:

Paranoid

The key feature of this subtype of schizophrenia is the combination of false beliefs (delusions) and hearing voices (auditory hallucinations), with more nearly normal emotions and cognitive functioning (cognitive functions include reasoning, judgment, and memory). The delusions of paranoid schizophrenics usually involve thoughts of being persecuted or harmed by others or exaggerated opinions of their own importance, but may also reflect feelings of jealousy or excessive religiosity. The delusions are typically organized into a coherent framework. Paranoid schizophrenics function at a higher level than other subtypes, but are at risk for suicidal or violent behavior under the influence of their delusions.

Disorganized

Disorganized schizophrenia (formerly called hebephrenic schizophrenia) is marked by disorganized speech, thinking, and behavior on the patient's part, coupled with flat or inappropriate emotional responses to a situation (affect). The patient may act silly or withdraw socially to an extreme extent. Most patients in this category have weak personality structures prior to their initial acute psychotic episode.

Catatonic

Catatonic schizophrenia is characterized by disturbances of movement that may include rigidity, stupor, agitation, bizarre posturing, and repetitive imitations of the movements or speech of other people. These patients are at risk for malnutrition, exhaustion, or self-injury. This subtype is presently uncommon in Europe and the United States. Catatonia as a symptom is most commonly associated with mood disorders.

Undifferentiated

Patients in this category have the characteristic positive and negative symptoms of schizophrenia but do not meet the specific criteria for the paranoid, disorganized, or catatonic subtypes.

Residual

This category is used for patients who have had at least one acute schizophrenic episode but do not presently have strong positive psychotic symptoms, such as delusions and hallucinations. They may have negative symptoms, such as withdrawal from others, or mild forms of positive symptoms, which indicate that the disorder has not completely resolved.

The risk of schizophrenia among first-degree biological relatives is ten times greater than that observed in the general population. Furthermore the presence of the same disorder is higher in monozygotic twins (identical twins) than in dizygotic twins (nonidentical twins). The research concerning adoption studies and identical twins also supports the notion that environmental factors are important, because not all relatives who have the disorder express it. There are several chromosomes and loci (specific areas on chromosomes which contain mutated genes), which have been identified. Research is actively ongoing to elucidate the causes, types and variations of these mutations.

Most patients are diagnosed in their late teens or early twenties, but the symptoms of schizophrenia can emerge at any age in the life cycle. The male/female ratio in adults is about 1.2:1. Male patients typically have their first acute episode in their early twenties, while female patients are usually closer to age 30 when they are recognized with active symptoms.

Schizophrenia is rarely diagnosed in preadolescent children, although patients as young as five or six have been reported. Childhood schizophrenia is at the upper end of the spectrum of severity and shows a greater gender disparity. It affects one or two children in every 10,000; the male/female ratio is 2:1.

Causes and symptoms

Theories of causality

One of the reasons for the ongoing difficulty in classifying schizophrenic disorders is incomplete understanding of their causes. It is thought that these disorders are the end result of a combination of genetic, neurobiological, and environmental causes. A leading neurobiological hypothesis looks at the connection between the disease and excessive levels of dopamine, a chemical that transmits signals in the brain (neurotransmitter). The genetic factor in schizophrenia has been underscored by recent findings that first-degree biological relatives of schizophrenics are ten times as likely to develop the disorder as are members of the general population.

Prior to recent findings of abnormalities in the brain structure of schizophrenic patients, several generations of psychotherapists advanced a number of psychoanalytic and sociological theories about the origins of schizophrenia. These theories ranged from hypotheses about the patient's problems with anxiety or aggression to theories about stress reactions or interactions with disturbed parents. Psychosocial factors are now thought to influence the expression or severity of schizophrenia rather than cause it directly.

As of 2004, migration is a social factor that is known to influence people's susceptibility to psychosis. Psychiatrists in Europe have noted the increasing rate of schizophrenia and other psychotic disorders among immigrants to almost all Western European countries. Black immigrants from Africa or the Caribbean appear to be especially vulnerable. The stresses involved in migration include family breakup, the need to adjust to living in large urban areas, and social inequalities in the new country.

Another hypothesis suggests that schizophrenia may be caused by a virus that attacks the hippocampus, a part of the brain that processes sense perceptions. Damage to the hippocampus would account for schizophrenic patients' vulnerability to sensory overload. As of 2004, researchers are focusing on the possible role of the herpes simplex virus (HSV) in schizophrenia, as well as human endogenous retroviruses (HERVs). The possibility that HERVs may be associated with schizophrenia has to do with the fact that antibodies to these retroviruses are found more frequently in the blood serum of patients with schizophrenia than in serum from control subjects.

Symptoms of schizophrenia

Patients with a possible diagnosis of schizophrenia are evaluated on the basis of a set or constellation of symptoms; there is no single symptom that is unique to schizophrenia. In 1959, the German psychiatrist Kurt Schneider proposed a list of so-called first-rank symptoms, which he regarded as diagnostic of the disorder.

These symptoms include:

• delusions
• somatic
• hallucinations
• hearing voices commenting on the patient's behavior
• thought insertion or thought withdrawal

Somatic hallucinations refer to sensations or perceptions concerning body organs that have no known medical cause or reason, such as the notion that one's brain is radioactive. Thought insertion and/or withdrawal refer to delusions that an outside force (for example, the FBI, the CIA, Martians, etc.) has the power to put thoughts into one's mind or remove them.

POSITIVE SYMPTOMS. The positive symptoms of schizophrenia are those that represent an excessive or distorted version of normal functions. Positive symptoms include Schneider's first-rank symptoms as well as disorganized thought processes (reflected mainly in speech) and disorganized or catatonic behavior. Disorganized thought processes are marked by such characteristics as looseness of associations, in which the patient rambles from topic to topic in a disconnected way; tangentially, which means that the patient gives unrelated answers to questions; and "word salad," in which the patient's speech is so incoherent that it makes no grammatical or linguistic sense. Disorganized behavior means that the patient has difficulty with any type of purposeful or goal-oriented behavior, including personal self-care or preparing meals. Other forms of disorganized behavior may include dressing in odd or inappropriate ways, sexual self-stimulation in public, or agitated shouting or cursing.

NEGATIVE SYMPTOMS. Schizophrenia includes three so-called negative symptoms. They are called negative because they represent the lack or absence of behaviors. The negative symptoms that are considered diagnostic of schizophrenia are a lack of emotional response (affective flattening), poverty of speech, and absence of volition or will. In general, the negative symptoms are more difficult for doctors to evaluate than the positive symptoms.

Diagnosis

A doctor must make a diagnosis of schizophrenia on the basis of a standardized list of outwardly observable symptoms, not on the basis of internal psychological processes. There are no specific laboratory tests that can be used to diagnose schizophrenia. Researchers have, however, discovered that patients with schizophrenia have certain abnormalities in the structure and functioning of the brain compared to normal test subjects. These discoveries have been made with the help of imaging techniques such as computed tomography scans (CT scans).

When a psychiatrist assesses a patient for schizophrenia, he or she will begin by excluding physical conditions that can cause abnormal thinking and some other behaviors associated with schizophrenia. These conditions include organic brain disorders (including traumatic injuries of the brain), temporal lobe epilepsy, Wilson's disease, prion diseases, Huntington's chorea, and encephalitis. The doctor will also need to rule out heavy metal poisoning and substance abuse disorders, especially amphetamine use.

After ruling out organic disorders, the clinician will consider other psychiatric conditions that may include psychotic symptoms or symptoms resembling psychosis. These disorders include mood disorders with psychotic features; delusional disorder; dissociative disorder not otherwise specified (DDNOS) or multiple personality disorder ; schizotypal, schizoid, or paranoid personality disorders ; and atypical reactive disorders. In the past, many individuals were incorrectly diagnosed as schizophrenic. Some patients who were diagnosed prior to the changes in categorization should have their diagnoses, and treatment, reevaluated. In children, the doctor must distinguish between psychotic symptoms and a vivid fantasy life, and also identify learning problems or disorders. After other conditions have been ruled out, the patient must meet a set of criteria specified:

• the patient must have two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms
• decline in social, interpersonal, or occupational functioning, including self-care
• the disturbed behavior must last for at least six months
• mood disorders, substance abuse disorders, medical conditions, and developmental disorders have been ruled out

Treatment

The treatment of schizophrenia depends in part on the patient's stage or phase. Psychotic symptoms and behaviors are considered psychiatric emergencies, and persons showing signs of psychosis are frequently taken by family, friends, or the police to a hospital emergency room. A person diagnosed as psychotic can be legally hospitalized against his or her will, particularly if he or she is violent, threatening to commit suicide, or threatening to harm another person. A psychotic person may also be hospitalized if he or she has become malnourished or ill as a result of failure to feed, dress appropriately for the climate, or otherwise take care of him- or herself.

A patient having a first psychotic episode should be given a CT or MRI (magnetic resonance imaging ) scan to rule out structural brain disease.

Antipsychotic medications

The primary form of treatment of schizophrenia is antipsychotic medication. Antipsychotic drugs help to control almost all the positive symptoms of the disorder. They have minimal effects on disorganized behavior and negative symptoms. Between 60-70% of schizophrenics will respond to antipsychotics. In the acute phase of the illness, patients are usually given medications by mouth or by intramuscular injection. After the patient has been stabilized, the antipsychotic drug may be given in a long-acting form called a depot dose. Depot medications last for two to four weeks; they have the advantage of protecting the patient against the consequences of forgetting or skipping daily doses. In addition, some patients who do not respond to oral neuroleptics have better results with depot form. Patients whose long-term treatment includes depot medications are introduced to the depot form gradually during their stabilization period. Most people with schizophrenia are kept indefinitely on antipsychotic medications during the maintenance phase of their disorder to minimize the possibility of relapse.

As of the early 2000s, the most frequently used antipsychotics fall into two classes: the older dopamine receptor antagonists, or DAs, and the newer serotonin dopamine antagonists, or SDAs. (Antagonists block the action of some other substance; for example, dopamine antagonists counteract the action of dopamine.) The exact mechanisms of action of these medications are not known, but it is thought that they lower the patient's sensitivity to sensory stimuli and so indirectly improve the patient's ability to interact with others.

DOPAMINE RECEPTOR ANTAGONIST. The dopamine antagonists include the older antipsychotic (also called neuroleptic) drugs, such as haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks: it is often difficult to find the best dosage level for the individual patient, and a dosage level high enough to control psychotic symptoms frequently produces extrapyramidal side effects, or EPS. EPSs include parkinsonism, in which the patient cannot walk normally and usually develops a tremor; dystonia, or painful muscle spasms of the head, tongue, or neck; and akathisia, or restlessness. A type of long-term EPS is called tardive dyskinesia, which features slow, rhythmic, automatic movements. Schizophrenics with AIDS are especially vulnerable to developing EPS.

SEROTONIN DOPANINE ANTAGONISTS. The serotonin dopamine antagonists, also called atypical antipsychotics, are newer medications that include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). The SDAs have a better effect on the negative symptoms of schizophrenia than do the older drugs and are less likely to produce EPS than the older compounds. The newer drugs are significantly more expensive in the short term, although the SDAs may reduce long-term costs by reducing the need for hospitalization. They are also presently unavailable in injectable forms. The SDAs are commonly used to treat patients who respond poorly to the DAs. However, many psychotherapists now regard the use of these atypical antipsychotics as the treatment of first choice; in particular, clozapine appears to be more effective than other antipsychotics in controlling persistent aggression in some patients.

NEWER DRUGS. Some newer antipsychotic drugs have been approved by the Food and Drug administration (FDA) in the early 2000s. These drugs are sometimes called second-generation antipsychotics or SGAs. Aripiprazole (Abilify), which is classified as a partial dopaminergic agonist, received FDA approval in August 2003. Two drugs that are still under investigation, a neurokinin antagonist and a serotonin 2A/2C antagonist respectively, show promise in the treatment of schizophrenia and schizoaffective disorder.

Psychotherapy

Most schizophrenics can benefit from psychotherapy once their acute symptoms have been brought under control by antipsychotic medication. Psychoanalytic approaches are not recommended. Behavior therapy, however, is often helpful in assisting patients to acquire skills for daily living and social interaction. It can be combined with occupational therapy to prepare the patient for eventual employment.

Family therapy

Family therapy is often recommended for the families of schizophrenic patients, to relieve the feelings of guilt that they often have as well as to help them understand the patient's disorder. The family's attitude and behaviors toward the patient are key factors in minimizing relapses (for example, by reducing stress in the patient's life), and family therapy can often strengthen the family's ability to cope with the stresses caused by the schizophrenic's illness. Family therapy focused on communication skills and problem-solving strategies is particularly helpful. In addition to formal treatment, many families benefit from support groups and similar mutual help organizations for relatives of schizophrenics.

Prognosis

One important prognostic sign is the patient's age at onset of psychotic symptoms. Patients with early onset of schizophrenia are more often male, have a lower level of functioning prior to onset, a higher rate of brain abnormalities, more noticeable negative symptoms, and worse outcomes. Patients with later onset are more likely to be female, with fewer brain abnormalities and thought impairment, and more hopeful prognoses.

The average course and outcome for schizophrenics are less favorable than those for most other mental disorders, although as many as 30% of patients diagnosed with schizophrenia recover completely and the majority experience some improvement. Two factors that influence outcomes are stressful life events and a hostile or emotionally intense family environment. Schizophrenics with a high number of stressful changes in their lives, or who have frequent contacts with critical or emotionally over-involved family members, are more likely to relapse. Overall, the most important component of long-term care of schizophrenic patients is complying with their regimen of antipsychotic medications.

KEY TERMS

Affective flattening— A loss or lack of emotional expressiveness. It is sometimes called blunted or restricted affect.

Akathisia— Agitated or restless movement, usually affecting the legs and accompanied by a sense of discomfort. It is a common side effect of neuroleptic medications.

Catatonic behavior— Behavior characterized by muscular tightness or rigidity and lack of response to the environment. In some patients rigidity alternates with excited or hyperactive behavior.

Delusion— A fixed, false belief that is resistant to reason or factual disproof.

Depot dosage— A form of medication that can be stored in the patient's body tissues for several days or weeks, thus minimizing the risk of the patient forgetting daily doses. Haloperidol and fluphenazine can be given in depot form.

Dopamine receptor antagonists (DAs)— The older class of antipsychotic medications, also called neuroleptics. These primarily block the site on nerve cells that normally receive the brain chemical dopamine.

Dystonia— Painful involuntary muscle cramps or spasms.

Extrapyramidal symptoms (EPS)— A group of side effects associated with antipsychotic medications. EPS include parkinsonism, akathisia, dystonia, and tardive dyskinesia.

First-rank symptoms— A set of symptoms designated by Kurt Schneider in 1959 as the most important diagnostic indicators of schizophrenia. These symptoms include delusions, hallucinations, thought insertion or removal, and thought broadcasting. First-rank symptoms are sometimes referred to as Schneiderian symptoms.

Hallucination— A sensory experience of something that does not exist outside the mind. A person can experience a hallucination in any of the five senses. Auditory hallucinations are a common symptom of schizophrenia.

Huntington's chorea— A hereditary disease that typically appears in midlife, marked by gradual loss of brain function and voluntary movement. Some of its symptoms resemble those of schizophrenia.

Negative symptoms— Symptoms of schizophrenia characterized by the absence or elimination of certain behaviors. DSM-IV specifies three negative symptoms: affective flattening, poverty of speech, and loss of will or initiative.

Neuroleptic— Another name for the older type of antipsychotic medications given to schizophrenic patients.

Parkinsonism— A set of symptoms originally associated with Parkinson disease that can occur as side effects of neuroleptic medications. The symptoms include trembling of the fingers or hands, a shuffling gait, and tight or rigid muscles.

Positive symptoms— Symptoms of schizophrenia that are characterized by the production or presence of behaviors that are grossly abnormal or excessive, including hallucinations and thought-process disorder. DSM-IV subdivides positive symptoms into psychotic and disorganized.

Poverty of speech— A negative symptom of schizophrenia, characterized by brief and empty replies to questions. It should not be confused with shyness or reluctance to talk.

Psychotic disorder— A mental disorder characterized by delusions, hallucinations, or other symptoms of lack of contact with reality. The schizophrenias are psychotic disorders.

Serotonin dopamine antagonist (SDA)— The newer second-generation antipsychotic drugs, also called atypical antipsychotics. SDAs include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa).

Wilson disease— A rare hereditary disease marked by high levels of copper deposits in the brain and liver. It can cause psychiatric symptoms resembling schizophrenia.

Word salad— Speech that is so disorganized that it makes no linguistic or grammatical sense.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., revised. Washington, D.C.: American Psychiatric Association, 2000.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Psychiatric Emergencies." Section 15, Chapter 194 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Schizophrenia and Related Disorders." Section 15, Chapter 193 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L. Stang. Nurse's Drug Guide 2003. Upper Saddle River, NJ: Prentice Hall, 2003.

PERIODICALS

DeLeon, A., N. C. Patel, and M. L. Crismon. "Aripiprazole: A Comprehensive Review of Its Pharmacology, Clinical Efficacy, and Tolerability." Clinical Therapeutics 26 (May 2004): 649-666.

Frankenburg, Frances R., MD. "Schizophrenia." eMedicine June 17, 2004. 〈http://www.emedicine.com/med/topic2072.htm〉.

Hutchinson, G., and C. Haasen. "Migration and Schizophrenia: The Challenges for European Psychiatry and Implications for the Future." Social Psychiatry and Psychiatric Epidemiology 39 (May 2004): 350-357.

Meltzer, H. Y., L. Arvanitis, D. Bauer, et al. "Placebo-Controlled Evaluation of Four Novel Compounds for the Treatment of Schizophrenia and Schizoaffective Disorder." American Journal of Psychiatry 161 (June 2004): 975-984.

Mueser, K. T., and S. R. McGurk. "Schizophrenia." Lancet 363 (June 19, 2004): 2063-2072.

Volavka, J., P. Czobor, K. Nolan, et al. "Overt Aggression and Psychotic Symptoms in Patients with Schizophrenia Treated with Clozapine, Olanzapine, Risperidone, or Haloperidol." Journal of Clinical Psychopharmacology 24 (April 2004): 225-228.

Yolken, R. "Viruses and Schizophrenia: A Focus on Herpes Simplex Virus." Herpes 11, Supplement 2 (June 2004): 83A-88A.

ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW, Washington DC 20005. (888) 357-7924. 〈http://www.psych.org〉.

National Alliance for the Mentally Ill (NAMI). Colonial Place Three, 2107 Wilson Blvd., Suite 300 Arlington, VA 22201. (703) 524-7600 HelpLine: (800) 950-NAMI. 〈http://www.nami.org/〉.

National Institute of Mental Health (NIMH). 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. 〈http://www.nimh.nih.gov〉.

Schizophrenics Anonymous. 15920 W. Twelve Mile, Southfield, MI 48076. (248) 477-1983.

United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. 〈http://www.fda.gov〉.

OTHER

"Schizophrenia." Internet Mental Health. 〈http://www.mentalhealth.com/dis/p20-ps01.html〉.

Schizophrenia

Definition

Schizophrenia is a psychotic disorder (or a group of disorders) marked by severely impaired thinking, emotions, and behaviors. Schizophrenic persons are typically unable to filter sensory stimuli and may have enhanced perceptions of sounds, colors, and other features of their environment. Most schizophrenics, if untreated, gradually withdraw from interactions with other people, and lose their ability to take care of personal needs and grooming.

Description

The course of schizophrenia in adults can be divided into three phases or stages. In the acute phase, a person has an overt loss of contact with reality (psychotic episode) that requires intervention and treatment. In the second or stabilization phase, the initial psychotic symptoms have been brought under control but the person is at risk for relapse if treatment is interrupted. In the third or maintenance phase, an individual is relatively stable and can be kept indefinitely on antipsychotic medications. Even in the maintenance phase, however, relapses are not unusual and people do not always return to full functioning.

The term schizophrenia comes from two Greek words that mean split mind. It was first used by a Swiss doctor named Eugen Bleuler in 1908 to describe the splitting apart of mental functions that he regarded as the central characteristic of schizophrenia.

Recently, some psychotherapists have begun to use a classification of schizophrenia based on two main types. People with Type I, or positive schizophrenia, have a rapid (acute) onset of symptoms and tend to respond well to drugs. They also tend to suffer more from so-called positive symptoms, such as delusions and hallucinations. People with Type II, or negative schizophrenia, are usually described as poorly adjusted before their schizophrenia slowly overtakes them. They have predominantly negative symptoms, such as withdrawal from others and a slowing of mental and physical reactions (psychomotor retardation).

The fourth (1994) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) specifies five subtypes of schizophrenia.

PARANOID. The key feature of this subtype of schizophrenia is the combination of false beliefs (delusions) and hearing voices (auditory hallucinations), with more nearly normal emotions and cognitive functioning (cognitive functions include reasoning, judgment, and memory ). The delusions of paranoid schizophrenics usually involve thoughts of being persecuted or harmed by others or exaggerated opinions of their own importance, but may also reflect feelings of jealousy or excessive religiosity. The delusions are typically organized into a coherent framework. Paranoid schizophrenics function at a higher level than other subtypes, but are at risk for suicidal or violent behavior under the influence of their delusions.

DISORGANIZED. Disorganized schizophrenia (formerly called hebephrenic schizophrenia) is marked by disorganized speech, thinking, and behavior by an affected person, coupled with flat or inappropriate emotional responses to a situation (affect). An individual may act silly or withdraw socially to an extreme extent. Most people in this category have weak personality structures prior to their initial acute psychotic episode.

CATATONIC. Catatonic schizophrenia is characterized by disturbances of movement that may include rigidity, stupor, agitation, bizarre posturing, and repetitive imitations of the movements or speech of other people. These people are at risk for malnutrition, exhaustion, or self-injury. This subtype is presently uncommon in Europe and the United States. Catatonia as a symptom is most commonly associated with mood disorders.

UNDIFFERENTIATED. Persons in this category have the characteristic positive and negative symptoms of schizophrenia but do not meet the specific criteria for the paranoid, disorganized, or catatonic subtypes.

RESIDUAL. This category is used for persons who have had at least one acute schizophrenic episode but do not presently have strong positive psychotic symptoms, such as delusions and hallucinations. They may have negative symptoms, such as withdrawal from others, or mild forms of positive symptoms, which indicate that the disorder has not completely resolved.

Genetic profile

The risk of schizophrenia among first-degree biological relatives is 10 times greater than that observed in the general population. Furthermore the presence of the same disorder is higher in monozygotic (identical) twins than in dizygotic (non-identical) twins. Research concerning adoption studies and identical twins also supports the notion that environmental factors are important, because not all relatives have the disorder or express it. There are several chromosomes and loci (specific areas on chromosomes that contain mutated genes) that have been identified. Research is ongoing to elucidate the causes, types and variations of these mutations.

Demographics

A number of studies indicate that about 1% of the world's population is affected by schizophrenia, without regard to race, social class, level of education, or cultural influences. The outcome may vary from culture to culture, depending on the familial support of an affected person. Most people are diagnosed in their late teens or early twenties, but the symptoms of schizophrenia can emerge at any age in the life cycle. The male to female ratio in adults is about 1.2:1. Males typically have their first acute episode in their early twenties, while females are usually closer to age 30 when they are recognized with active symptoms.

Schizophrenia is rarely diagnosed in preadolescent children, although individuals as young as five or six have been reported. Childhood schizophrenia is at the upper end of the spectrum of severity and shows a greater gender disparity. It affects one or two children in every 10,000; the male to female ratio is 2:1.

Causes and symptoms

Theories of causality

One of the reasons for the ongoing difficulty in classifying schizophrenic disorders is incomplete understanding of their causes. As of 2001, it is thought that these disorders are the end result of a combination of genetic, neurobiological, and environmental causes. A leading neurobiological hypothesis emphasizes the connection between the disease and excessive levels of dopamine, a chemical that transmits signals in the brain (neurotransmitter). The genetic factor in schizophrenia has been underscored by recent findings that first-degree biological relatives of schizophrenics are 10 times more likely to develop the disorder than are members of the general population.

Prior to recent findings of abnormalities in the brain structure of schizophrenic persons, several generations of psychotherapists advanced a number of psychoanalytic and sociological theories about the origins of schizophrenia. These theories ranged from hypotheses about a person's problems with anxiety or aggression to theories about stress reactions or interactions with disturbed parents. Psychosocial factors are now thought to influence the expression or severity of schizophrenia, rather than directly cause it.

Another hypothesis suggests that schizophrenia may be caused by a virus that attacks the hippocampus, a part of the brain that processes sense perceptions. Damage to the hippocampus would account for a schizophrenic person's vulnerability to sensory overload. As of mid-2001, researchers are testing antiviral medications on schizophrenics.

Symptoms of schizophrenia

People with a possible diagnosis of schizophrenia are evaluated on the basis of a set or constellation of symptoms. There is no single symptom that is unique to schizophrenia. In 1959, the German psychiatrist Kurt Schneider proposed a list of so-called first-rank symptoms, which he regarded as diagnostic of the disorder.

These symptoms include:

• delusions
• somatic hallucinations
• hallucinations
• hearing voices commenting on a person's behavior
• thought insertion or thought withdrawal

Somatic hallucinations refer to sensations or perceptions concerning body organs that have no known medical cause or reason, such as the notion that one's brain is radioactive. Thought insertion and/or withdrawal refer to delusions that an outside force (for example, the FBI, the CIA, Martians, etc.) has the power to put thoughts into one's mind or remove them.

POSITIVE SYMPTOMS. The positive symptoms of schizophrenia are those that represent an excessive or distorted version of normal functions. Positive symptoms include Schneider's first-rank symptoms as well as disorganized thought processes (reflected mainly in speech) and disorganized or catatonic behavior. Disorganized thought processes are marked by such characteristics as looseness of association, in which a person rambles from topic to topic in a disconnected way; tangentiality, which means that an individual gives unrelated answers to questions; and flights of ideas or "word salad," in which a person's speech is so incoherent that it makes no grammatical or linguistic sense. Disorganized behavior means that a person has difficulty with any type of purposeful or goal-oriented behavior, including personal self-care or preparing meals. Other forms of disorganized behavior may include dressing in odd or inappropriate ways, sexual self-stimulation in public, or agitated shouting or cursing.

NEGATIVE SYMPTOMS. The DSM-IV definition of schizophrenia includes three so-called negative symptoms. They are called negative because they represent the lack or absence of behaviors. The negative symptoms that are considered diagnostic of schizophrenia are a lack of emotional response (affective flattening), poverty of speech, and absence of volition or will. In general, the negative symptoms are more difficult for doctors to evaluate than the positive symptoms.

Diagnosis

A doctor must make a diagnosis of schizophrenia on the basis of a standardized list of outwardly observable symptoms, not on the basis of internal psychological processes. There are no specific laboratory tests that can be used to diagnose schizophrenia. Researchers have, however, discovered that persons with schizophrenia have certain abnormalities in the structure and functioning of the brain compared to normal test subjects. These discoveries have been made with the help of imaging techniques such as computed tomography scans (CT scans ).

When a psychiatrist assesses an individual for schizophrenia, the doctor will begin by excluding physical conditions that can cause abnormal thinking and some other behaviors associated with schizophrenia. These conditions include organic brain disorders (including traumatic injuries of the brain), temporal lobe epilepsy, Wilson's disease, Huntington's chorea, and encephalitis. The doctor will also need to rule out substance abuse disorders, especially amphetamine use.

After ruling out organic disorders, a clinician will consider other psychiatric conditions that may include psychotic symptoms or symptoms resembling psychosis. These disorders include mood disorders with psychotic features; delusional disorder; dissociative disorder not otherwise specified (DDNOS) or multiple personality disorder; schizotypal, schizoid, or paranoid personality disorders ; and atypical reactive disorders. In the past, many individuals were incorrectly diagnosed as being schizophrenic. Some people who were diagnosed prior to the changes in categorization introduced by DSM-IV should have their diagnoses, and treatment, reevaluated. In children, a doctor must distinguish between psychotic symptoms and a vivid fantasy life, and also identify learning problems or disorders. After other conditions have been ruled out, a person must meet a set of criteria specified by DSM-IV:

• Characteristic symptoms. To make a diagnosis of schizophrenia, a person must exhibit two (or more) of the following symptoms during a one-month period: delusions; hallucinations; disorganized speech; disorganized or catatonic behavior; negative symptoms.
• Decline in social, interpersonal, or occupational functioning, including self-care.
• Duration. The disturbed behavior must last for at least six months.
• Diagnostic exclusions. Mood disorders, substance abuse disorders, medical conditions, and developmental disorders have been ruled out.

Treatment

The treatment of schizophrenia depends in part on an individual's stage or phase. People in the acute phase are hospitalized in most cases, to prevent harm to themselves or to others and to begin treatment with antipsychotic medications. A person having a first psychotic episode should be given a CT (computed tomography) or MRI (magnetic resonance imaging ) scan to rule out structural brain abnormalities or disease.

Antipsychotic medications

The primary form of treatment of schizophrenia is antipsychotic medication. Antipsychotic drugs help to control almost all the positive symptoms of the disorder. They have minimal effect on disorganized behavior and negative symptoms. Between 60–70% of schizophrenics will respond to antipsychotics. In the acute phase of the illness, people are usually given medications by mouth or by intramuscular injection . After an affected person has been stabilized, the antipsychotic drug may be given in a long-acting form called a depot dose. Depot medications last for two to four weeks and have the advantage of protecting a person against the consequences of forgetting or skipping daily doses. In addition, some people who do not respond to oral neuroleptic medications have better results with depot form. Persons whose long-term treatment includes depot medications are introduced to the depot form gradually during their stabilization period. Most people with schizophrenia are kept on antipsychotic medications indefinitely during the maintenance phase of their disorder to minimize the possibility of relapse.

As of 2001, the most frequently used antipsychotics fall into two classes: the older dopamine receptor antagonists, or DAs, and the newer serotonin dopamine antagonists, or SDAs. Antagonists block the action of some other substance. For example, dopamine antagonists counteract the action of dopamine. The exact mechanisms of action of these medications are not known, but it is thought that they lower a person's sensitivity to sensory stimuli and so indirectly improve the person's ability to interact with others.

DOPAMINE RECEPTOR ANTAGONIST. The dopamine antagonists include the older antipsychotic (also called neuroleptic) drugs, such as haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin). These drugs have two major drawbacks. It is often difficult to find the best dosage level for a given individual, and a dosage level high enough to control psychotic symptoms frequently produces extrapyramidal side effects, or EPS. EPSs include parkinsonism, in which a person cannot walk normally and usually develops a tremor; dystonia, or painful muscle spasms of the head, tongue, or neck; and akathisia, or restlessness. A type of long-term EPS is called tardive dyskinesia, which features slow, rhythmic, automatic movements. Schizophrenics with AIDS are especially vulnerable to developing EPS.

SERATONIN DOPAMINE ANTAGONISTS. The serotonin dopamine antagonists, also called atypical antipsychotics, are newer medications that include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa). The SDAs have a better effect on the negative symptoms of schizophrenia than do the older drugs and are less likely to produce EPS than the older compounds. The newer drugs are significantly more expensive in the short term, although the SDAs may reduce long-term costs by reducing the need for hospitalization. They are also presently unavailable in injectable forms. The SDAs are commonly used to treat persons who respond poorly to the DAs. However, many psychotherapists now regard the use of these atypical antipsychotics as the treatment of first choice.

Psychotherapy

Most schizophrenics can benefit from psychotherapy once their acute symptoms have been brought under control by antipsychotic medication. Psychoanalytic approaches are not recommended. Behavior therapy, however, is often helpful in assisting people to acquire skills for daily living and social interaction. It can be combined with occupational therapy to prepare individuals for eventual employment.

Family therapy

Family therapy is often recommended for the families of schizophrenic patients, to relieve the feelings of guilt that they often have as well as to help them understand a schizophrenic's disorder. The family's attitude and behaviors toward the schizophrenic are key factors in minimizing relapses (for example, by reducing stress in an individual's life), and family therapy can often strengthen the family's ability to cope with the stresses caused by the schizophrenic's illness. Family therapy that focuses on communication skills and problem-solving strategies is particularly helpful. In addition to formal treatment, many families benefit from support groups and similar mutual help organizations for relatives of schizophrenics.

KEY TERMS

Affective flattening —A loss or lack of emotional expressiveness. It is sometimes called blunted or restricted affect.

Akathisia —Agitated or restless movement, usually affecting the legs and accompanied by a sense of discomfort. It is a common side effect of neuroleptic medications.

Catatonic behavior —Behavior characterized by muscular tightness or rigidity and lack of response to the environment. In some persons, rigidity alternates with excited or hyperactive behavior.

Delusion —A fixed, false belief that is resistant to reason or factual disproof.

Depot dosage —A form of medication that can be stored in a person's body tissues for several days or weeks, thus minimizing the risk of forgetting daily doses. Haloperidol and fluphenazine can be given in depot form.

Dopamine receptor antagonists (DAs) —The older class of antipsychotic medications, also called neuroleptics. These primarily block the site on nerve cells that normally receives the brain chemical dopamine.

Dystonia —Painful involuntary muscle cramps or spasms. Dystonia is one of the extrapyramidal side effects associated with some antipsychotic medications.

Extrapyramidal symptoms (EPS) —A group of side effects associated with antipsychotic medications. EPS include parkinsonism, akathisia, dystonia, and tardive dyskinesia.

First-rank symptoms —A set of symptoms designated by Kurt Schneider in 1959 as the most important diagnostic indicators of schizophrenia. These symptoms include delusions, hallucinations, thought insertion or removal, and thought broadcasting. First-rank symptoms are sometimes referred to as Schneiderian symptoms.

Hallucination —A sensory experience of something that does not exist outside the mind. A person can experience a hallucination in any of the five senses. Auditory hallucinations are a common symptom of schizophrenia.

Huntington's chorea —A hereditary disease that typically appears in midlife, marked by gradual loss of brain function and involuntary movements. Some of its symptoms resemble those of schizophrenia.

Negative symptoms —Symptoms of schizophrenia that are characterized by the absence or elimination of certain behaviors. DSM-IV specifies three negative symptoms: affective flattening, poverty of speech, and loss of will or initiative.

Neuroleptic —Another name for the older type of antipsychotic medications given to schizophrenic persons.

Parkinsonism —A set of symptoms originally associated with Parkinson's disease that can occur as side effects of neuroleptic medications. The symptoms include trembling of the fingers or hands, a shuffling gait, and tight or rigid muscles.

Positive symptoms —Symptoms of schizophrenia that are characterized by the production or presence of behaviors that are grossly abnormal or excessive, including hallucinations and thought process disorder. DSM-IV subdivides positive symptoms into psychotic and disorganized.

Poverty of speech —A negative symptom of schizophrenia, characterized by brief and empty replies to questions. It should not be confused with shyness or reluctance to talk.

Psychotic disorder —A mental disorder characterized by delusions, hallucinations, or other symptoms of lack of contact with reality. The schizophrenias are psychotic disorders.

Serotonin dopamine antagonists (SDAs) —The newer second-generation antipsychotic drugs, also called atypical antipsychotics. SDAs include clozapine (Clozaril), risperidone (Risperdal), and olanzapine (Zyprexa).

Wilson's disease —A rare hereditary disease marked by high levels of copper deposits in the brain, eyes and liver. It can cause psychiatric symptoms resembling schizophrenia.

Word salad —Speech that is so disorganized that it makes no linguistic or grammatical sense.

Prognosis

One important prognostic sign is a person's age at onset of psychotic symptoms. People with early onset of schizophrenia are more often male, have a lower level of functioning prior to onset, a higher rate of brain abnormalities, more noticeable negative symptoms, and worse outcomes. Persons with later onset are more likely to be female, with fewer brain abnormalities and thought impairment, and more hopeful prognoses.

The average course and outcome for schizophrenics are less favorable than those for most other mental disorders, although as many as 30% of people diagnosed with schizophrenia recover completely and the majority experience some improvement. Two factors that influence outcomes are stressful life events and a hostile or emotionally intense family environment. Schizophrenics with a high number of stressful changes in their lives, or who have frequent contacts with critical or emotionally overinvolved family members, are more likely to relapse. Overall, the most important component of long-term care for schizophrenic individuals is complying with their regimen of antipsychotic medications.

Health care team roles

Physicians such as a family doctor or internist often make an initial diagnosis of schizophrenia. Psychiatrists, psychologists, or other therapists may also provide an initial diagnosis. Psychiatrists, clinical psychologists, or other trained professionals provide intervention treatment and therapy. Counselors may provide support during and after treatment. Nurses often administer medications.

Prevention

With present levels of understanding about schizophrenia, there does not appear to be any way to prevent the disease. Better understanding holds the promise of prevention if specific causal factors are environmental, chemical or viral.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association, 1994.

Brenner, H.D., and R. Boker. Treatment of Schizophrenia: Status and Emerging Trends. Seattle: Hogrefe & Huber, 2001.

Corrigan, Patrick W., and David L. Penn. Social Cognition and Schizophrenia. Washington, DC: American Psychological Association, 2001.

Dalton, Richard, and Marc A. Forman. "Childhood schizophrenia." In Nelson Textbook of Pediatrics, 16th ed. Edited by Richard E. Behrman et al., Philadelphia: Saunders, 2000, 88-89.

Green, Michael F. Schizophrenia Revealed: From Neurons to Social Interaction. New York: W.W. Norton, 20001.

Sharma, Tonmoy, and Philip D. Harvey. Cognition in Schizophrenia: Impairments, Importance, and Treatment Strategies. New York: Oxford University Press, 2000.

Warner, Richard. The Environment of Schizophrenia: Innovations in Practice, Policy and Communications. New York: Warner, 2001.

PERIODICALS

Mason, SE, Miller R. Bulletin of the Menninger Clinic 65, no. 2 (2001): 179-193.

Meltzer, HY. "Treatment of suicidality in schizophrenia." Annals of the New York Academy of Science 932 (2001): 44-60.

Rungreangkulkij, S, Chesla C. "Smooth a heart with water: Thai mothers care for a child with schizophrenia." Archives of Psychiatric Nursing 15, no. 3 (2001): 120-127.

Sanders, AR, Gejman PV. "Influential Ideas and Experimental Progress in Schizophrenia Genetics Research." Journal of the American Medical Association 13, 285, no. 22(2001): 2831-2833.

Thaker, G, Adami H, Gold J. "Functional deterioration in individuals with schizophrenia spectrum personality symptoms." Journal of Personality Disorders 15, no. 3 (2001): 229-234.

Wiedemann, G, Hahlweg K, Muller U, Feinstein E, Hank G, Dose M. "Effectiveness of targeted intervention and maintenance pharmacotherapy in conjunction with family intervention in schizophrenia." European Archives of Psychiatry and Clinical Neuroscience 251, no. 2 (2001): 72-84.

ORGANIZATIONS

American Psychological Association. 750 First Street NW, Washington, DC, 20002-4242. (800) 374-2721 or (202) 336-5500. <http://www.apa.org/>.

National Alliance for Research on Schizophrenia and Depression. 60 Cutter Mill Road, Suite 404, Great Neck, NY 11021. (516) 829-0091. Fax: (516) 487-6930. <http://www.mhsource.com/narsad/>. [email protected].

National Institute of Mental Health. 6001 Executive Boulevard, Rm. 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. Fax (301) 443-4279. <http://www.nimh.nih.gov/home.cfm>. [email protected].

National Mental Health Association. 1021 Prince Street, Alexandria, VA 22314-2971. (800) 969-6942 or (703) 684-7722. Fax: (703) 684-5968. <http://www.nmha.org/>.

OTHER

American Academy of Child and Adolescent Psychiatry. <http://www.aacap.org/publications/factsfam/schizo.htm>.

Mental Health Source. <http://www.mhsource.com/schizophrenia/>.

Merck Manual. <http://www.merck.com/pubs/mmanual/section15/chapter193/193a.htm>.

National Institute of Mental Health. <http://www.nimh.nih.gov/publicat/schizsoms.cfm>.

National Library of Medicine. <http://www.nlm.nih.gov/medlineplus/schizophrenia.html>.

Schizophrenia Society of Canada. <http://www.schizophrenia.ca/refmanualindesign.html>.

World Fellowship for Schizophrenia and Allied Disorders. <http://www.world-schizophrenia.org/>.

L. Fleming Fallon, Jr., MD, DrPH