THE SCHIZOPHRENIAS AND PARANOID STATES
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receptors in the brains of schizophrenic patients (see later) A further connection is based on the nding by Williams and colleagues of an allelic variation in the gene on chromosome 13 encoding for a serotonin receptor (5-HT2A) that confers a susceptibility to schizophrenia A similar nding has been reported in a Japanese population The variation in this gene is not suf cient to explain the presence of the disease in any one individual, if for no other reason than that many patients who are homozygous for the suspect allele do not develop schizophrenia Perhaps a nearby region relating to the receptor may be at fault through linkage disequilibrium (see commentary by Harrison and Geddes) A third hypothesis derives from the psychosis syndrome produced by chronic ingestion of phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) antagonist This implicates the glutaminergic system but it must be pointed out that the dopaminergic and glutaminergic systems converge on certain cortical neurons and that glutaminergic release is modulated in several places in the brain by dopamine A great variety of physiologic and endocrine differences between schizophrenic and healthy subjects have been claimed None has proved to be signi cant Since psychoses may complicate corticosteroid administration and certain endocrine disorders (Cushing syndrome, thyrotoxicosis, see later), there have been many attempts to uncover such abnormalities in the schizophrenic patient All have failed Psychosocial Hypotheses The notion that psychosocial factors play an important role in the genesis of schizophrenia was a recurrent theme in older psychiatric writings but is now given little credence Prominent in these early writings was Freud s view, already mentioned, that the schizophrenic process represents a xation at an early autoerotic stage of sexual development There is no way of af rming or refuting this proposition The same can be said for the many suggestions that disturbed intrafamily relationships engender schizophrenic traits or possibly provoke psychosis in persons who are genetically vulnerable Behind all these suggestions was the notion that disturbed interpersonal relations in the family in some way interfered with the normal maturation of personality Adolf Meyer believed that schizophrenia was a reaction to a series of traumatic life situations a maladaptive response to some organic, psychologic, or sociologic factor Others have stressed the importance of disturbed interpersonal relationships However, with all these hypotheses, proof is lacking that such environmental factors are unique to the development of schizophrenia Furthermore, the extent to which these aberrations of family relationships are primary or secondary cannot be ascertained The often-cited observations of Harlow on the deleterious effects of maternal and peer deprivation in primates opened the possibility that similar deprivations in humans may be responsible for the development of schizophrenia However, such severe degrees of familial deprivation have rarely been documented in humans and when they were, as in some orphans, the effects were only transitory
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sional-hallucinatory syndrome in which there is little if any disturbance of consciousness Although such a syndrome is characteristic of schizophrenia, it may occur in the manic phase of manic-depressive disease, encephalitis, temporal lobe epilepsy, chronic amphetamine intoxication, withdrawal from alcohol after a sustained period of intoxication, and most often in the emergency department, PCP, angel dust, LSD, and other drug intoxications On rare occasions it is seen with postpartum psychosis (see further on) and with certain endocrine and metabolic disorders, in which consciousness is not impaired Whenever this syndrome is recognized, therefore, these several causes need to be differentiated On our services, less than one out of ve of the acute schizophreniform psychoses have proved to be due to the disease schizophrenia This distinction is made by the premorbid history and the course of the illness Restated, a longitudinal observation is necessary before concluding that a particular acute syndrome is due to schizophrenia If the patient had been reclusive, withdrawn, and socially maladept and does not seem to recover fully from the acute psychosis, then the diagnosis of schizophrenia is more likely Lacking these features, and in particular with a full remission, one assumes the occurrence of hypomania or of a toxic-metabolic psychosis, which can usually be detected by laboratory screening for drugs and endocrine diseases Only 10 percent of patients with classic schizophrenia will have such an acute episode Adherence to the criteria enumerated earlier, particularly to those devised by Feighner and colleagues, will avoid most errors in diagnosis It is the present authors opinion that the status of acute schizophrenia and of the so-called schizothymic and schizoaffective states brings to light a crucial nosologic problem Namely, is the traditional separation of depressive disease, manic-depressive disease, and schizophrenia biologically sound The suggestion is that they are linked in some way by these transitional forms Neurologists should keep an open mind about these and other theoretical problems that lack a rm genetic and neuropathologic basis In addition to the acute schizophreniform psychosis described earlier, the authors have encountered the greatest dif culties in the diagnosis of schizophrenia in the following clinical situations: A patient with a healthy family and premorbid history with an acute illness having many of the typical features of schizophrenia but associated with confusion, forgetfulness, and/or clouding of consciousness Mood change may be prominent Thus the illness combines the features of an affective disorder, schizophrenia, and a confusional state This syndrome is characteristic of chronic hallucinogenic drug use, particularly phencyclidine intoxication, corticosteroid psychosis (drug-induced or Cushing disease), thyrotoxic psychosis, puerperal psychosis, and combat fatigue of wartime Usually recovery is complete, and schizophrenia is excluded by the fact that the patient remains well This may be a form of schizoaffective disorder 2 Adolescents and young adults whose social relationships are disorganized and who are unusually sensitive, resentful, rebellious, fearful, discouraged, in trouble with school authorities and the law, and using drugs The latter may have caused seizures, hallucinations, and withdrawal symptoms or may have resulted in addiction Such patients are usually classi ed as having a borderline personality or character disorder that appears to go back several years; if they are incorrigible, unable to pro t by experience, amoral, and in trouble with social agencies, they are called sociopaths This 1
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