HLA antigens and 19 other genetic marker systems were studied in 12 families containing 2 or more members diagnosed as schizophrenic. In contrast with previous reports we could exclude linkage between the disorder and HLA, and we found no evidence of linkage with Gm or Ge. The disagreement between our results and those of a previous study, which suggested linkage between HLA and schizophrenia, could not be explained on the basis of genetic heterogeneity within the disorder. The problems of performing a linkage study in the face of diagnostic uncertainty and an unknown mode of inheritance of the main trait are discussed, and the measures taken in attempts to overcome these difficulties are described. Despite present drawbacks, genetic marker studies hold future promise as a means of detecting major gene effects in schizophrenia and other familial psychiatric disorders.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (Huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2½ years.

Analysis of variance on data obtained from behavioural observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2½ years after injection by automated activity monitoring.

There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation.

Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.

Dangerous and even fatal interactions can occur in man following combinations of antidepressants which include non-selective MAO inhibitors. To ascertain the causation, interactions reproducing the clinical phenomena have been elicited in animals with these combinations, and the mechanisms involved have been explored by various pharmacological strategies; 5-HT re-uptake inhibitors proved especially hazardous in combination. Interactions could, however, be avoided even with the 5-HT re-uptake inhibitors, by combination with relatively selective MAO A or B inhibitors, an approach with potential clinical value.

The frequencies of various forms of eating-related behaviour (such as vomiting and laxative abuse) are reported for a series of non-anorectic bulimia patients seen for evaluation in an eating disorders clinic. The results of serum electrolyte, glucose and other screening tests in these patients are presented. Electrolyte abnormalities were found in 82 of the 168 patients (48·8%) who were diagnosed as having either bulimia or atypical eating disorder. The most common abnormality was metabolic alkalosis (27·4%); hypochloremia (23·8%) and hypokalemia (13·7%) were also commonly seen. No significant blood sugar abnormalities were encountered. An elevated serum amylase level was found to be associated with frequent binge-eating and vomiting behaviour. The pathophysiology of electrolyte abnormalities in this patient group is briefly reviewed.

Twelve manic patients were treated for 2 weeks with oral haloperidol; in 6 patients treatment commenced with intravenous haloperidol, and intravenous ‘test’ doses were given after 1, 3–5 and 14 days of oral medication. From 24 hours to 14 days baseline serum prolactin levels rose towards a plateau, as did the improvement in clinical ratings. After the first intravenous test doses of haloperidol, prolactin levels peaked at 1 hour; however, they fell to a low point at 24 hours, and no response to further test doses was seen for 3–5 days. The response tended to return at 14 days. The mechanisms underlying the changes in prolactin levels, and in clinical state, are discussed.

In a series of 36 patients with acute schizophrenia flupenthixol dosage was blindly adjusted to give a fixed level of sedation. Patients were then randomly allocated to procyclidine or placebo. The patients receiving procyclidine experienced more positive schizophrenic symptoms and less severe extrapyramidal features by comparison with placebo patients. Blood levels of prolactin and flupenthixol estimated by radloimmunoassay were not significantly changed by the addition of procyclidine. Flupenthixol dosage and levels and prolactin levels were significantly related. There was no significant association between clinical and laboratory measures, with the exception that a curvilinear (inverted U) relationship was demonstrated between flupenthixol levels and antipsychotic and extrapyramidal effects. This relationship may be due to the fact that, in a study of this design, patients resistant to the effects of neuroleptic medication are likely to be given the highest doses. The findings support earlier claims that anticholinergic medication has adverse effects on schizophrenic symptoms.

The rate of occurrence of conduct disorder and affective illness was studied for a sample of 112 offspring of 34 Huntington's Disease (HD) patients. Psychiatric disorder in the offspring was assessed as a function of: (1) age of the parent at the onset of symptoms of HD; (2) family disorganization; and (3) psychiatric disorder in either parent. The findings indicated an increased frequency of conduct disorder in disrupted families, most especially in those where the HD parent had an early onset of symptoms and the non-HD parent showed psychiatric disorder. Affective disorder in the offspring was most strongly associated with the presence of similar symptoms in the HD parent. Affective disorder, but not conduct disorder, may be an early manifestation of the HD gene. The implication of these findings for genetic counselling is discussed.

When amphetamines are administered to humans every few hours for several days, either during the ‘speed runs’ of addicts or in controlled laboratory settings, the psychosis which reliably results is similar to paranoid schizophrenia in a number of important aspects. This unique regimen of drug intake, which involves the continuous presence of stimulants over a prolonged period of time, can be simulated in animals using subcutaneously implanted slow-release silicone pellets containing d-amphetamine base. Monkeys and rats implanted with these pellets develop stages of behavioural alterations which are somewhat similar in sequence to those observed in humans who have received frequent doses of amphetamine. An initial period of hyperactivity and exploratory behaviour is followed by the gradual development of motor stereotypies which become virtually incessant. A period of relative inactivity then appears which is followed, at 4–5 days after pellet implantation, by a late stage. This final stage is characterized by ‘wet-dog’ shakes, parasitotic-like grooming episodes, and a variety of other forms of hallucinatory-like behaviour. At about the same time there are distinctive and partially irreversible alterations in dopaminergic innervations of the caudate nucleus, but not in mesolimbic dopamine innervation of the nucleus accumbens or in several other neurotransmitter systems. Continuous amphetamine administration may reproduce some aspects of the prolonged excitation which accompanies an acute psychotic episode and may be a fruitful model for the clarification of the dopamine theory of schizophrenia.

One hundred and sixty-six unipolar and bipolar out-patients (21–78 years) on long-term lithium treatment were studied on a prospective basis. Although there was a possible tendency for manic attacks to increase in prevalence and severity with age, it was difficult to demonstrate a general age-related decline in lithium efficacy. There was a tendency for the prevalence and severity of fine hand tremor to increase with age. This was not seen with polydipsia/polyuria, the other typical lithium side-effect.

The study explored associations between the cerebral event-related slow potentials (ERSP) and psychiatric symptoms and syndromes as reflected by the Present State Examination (PSE) in 36 randomly selected psychiatric in-patients. Independent raters measured the readiness potential (RP), contingent negative variation (CNV) and post-imperative negative variation (PINV) in terms of their amplitude and duration. The 360 individual PSE items were grouped into units of analysis (UA) and further collapsed into groups of units of analysis (GUA). Canonical correlations were computed between two sets of variables (psychological and electrophysiological). Kendall's rank-order correlation was used as the main statistical approach. Some psychotic signs were associated with increased PINV amplitude. Obsessive thoughts, ideas of reference and verbal hallucinations correlated with longer PINV duration. Hopelessness and suicidal thoughts (affect-laden thoughts) as well as first-rank Schneiderian symptoms (FRS) were negatively correlated with CNV amplitude. The results support the hypothesis that CNV and PINV, alone or in combination, can be used to indicate the presence or absence of identifiable psychiatric symptoms and syndromes. The implications of electrophysiological correlates of psychopathology for psychiatric nosology and for the validity of psychiatric symptoms and syndromes were discussed

Memory functions were examined in a group of 53 patients with affective disorders before commencing prophylactic lithium therapy and then after 4 and 12 months of lithium treatment. The memory tests administered were the 30 Figure Test, the 30 Word-Pair Test, the 30 Person-Data Test (these tests are included in the Cronhoim–Molander test battery) and the 30 Face Test. Three scores were obtained: immediate memory score, delayed memory score and forgetting score. There were no statistical significant differences between these scores before lithium therapy or after 4 and 12 months, except for immediate and delayed memory on the Person-Data Test and the 30 Face Test which showed an increased score of memory functions. The results of this study support the view that long-term lithium treatment with serum levels of about 0·6 mmol/1 does not induce memory disturbances.

Electrodermal, electroencephalographic and perceptual measures of lateral hemispheric function were obtained from groups of chronic schizophrenics, depressives and normals on 2 occasions, separated by 4 weeks. The measures of hemispheric function were derived from previous research. About half of the schizophrenics were medicated on both occasions; the other schizophrenics underwent drug ‘washout’ before the first session. Results revealed that the measures of laterality were not strongly intercorrelated. In the perceptual task, the schizophrenics and normals displayed different laterality effects. Unlike the normals, the schizophrenics' left hemisphere function appeared to be inferior to the right hemisphere function in the perceptual task. The laterality effects of the depressives and normals differed on two electrodermal measures: skin conductance level and skin conductance response amplitude. The depressives' electrodermal activity from the right hand was diminished as compared with the left hand; the normals did not show this effect. Medication decreased electrodermal activity in the schizophrenics, but had no significant effect on laterality. These results suggest that the various measures of laterality used singly in previous research in psychopathology may not all assess the same phenomenon.

Bouffée délirante is an historic and unique French diagnostic term for a short-lived psychosis. The key diagnostic features are acute, floridly psychotic symptoms with complete remission. Its use in a Paris hospital has been examined, and it appears that the term is declining in popularity. A case-controlled study indicated that the diagnosis is likely to be given to migrants on first admission. A re-diagnosis of case summaries indicated no particular correspondence of bouffée délirante to any one lCD category. However, the usefulness of having a special diagnostic term for psychosis with a good outcome is discussed.

Major affective disorder clinically similar to the disorder found in conditions other than Huntington's Disease (HD) was found in 41% of patients with HD in a consecutive case series ascertained through multiple sources in a defined geographical area. The association appears to be confined to certain families, and affective disorder may appear as long as 20 years before the onset of chorea and dementia. The association may represent genetic heterogeneity in HD.

The EEG synchrony between hemispheres during cognitive activity differs from that during rest. With common reference recording and a visual imagery task it increases in healthy right-handers and neurotic patients, and it decreases in healthy left-handers and schizophrenic patients. It is suggested that this implies a less lateralized brain organization in schizophrenia which may account for the often reported association with left-handedness. When associated with impaired corpus callosum transmission, it may contribute to the disturbed behaviour and thought processes in this condition.

Renal concentrating capacity following 18 hours of fluid deprivation was measured in 75 patients receiving prophylactic lithium therapy, and in 30 affectively ill subjects receiving other drugs. The lithium-treated patients had significantly lower urine osmolality and higher serum osmolality than the control subjects. Older subjects, patients maintained at higher serum lithium levels and those with a history of previous neurotoxicity showed the most impairment. Ten patients with urine osmolalities of less than 700 mOsm/l following this test were investigated further. Inulin and para-amino hippurate (PAH) clearance rates were determined and the effect of a subpressor challenge of dopamine on these measures was observed. Half of the patients showed some reduction in inulin and PAH clearance, which was greatest in those patients who had been taking lithium for over 10 years. However, all of the patients tested showed the expected increase in renal blood flow and sodium and water excretion in response to dopamine. Six additional patients had clearance estimations made before starting lithium treatment which were repeated after a period of 3–6 months on the drug. No consistent changes in haemodynamics were observed.

Lithium clearly reduces renal concentrating capacity, but other measures of renal tubular function were well preserved in patients receiving long-term therapy. Glomerular function may be slightly reduced in patients taking lithium for long periods. The results show that prophylactic lithium treatment does not affect renal cortical function adversely in the majority of patients, but impaired renal concentrating ability is a common accompaniment.

A review of the literature describing patients with functional visual loss reveals that a significant proportion of them do not manifest psychiatric disease as defined by current nomenclature. Apparently, these individuals are highly suggestible and do not necessarily have psychological pathology. The ramifications of this finding are discussed.

Within a sample of 141 female anorexia nervosa patients comparative investigations were carried out between three subgroups: dieters, binge-eaters, and vomiters/purgers. A number of significant differences were found, especially with respect to age and duration of illness, previous treatment failures, and long-term outcome. The results appear to support the authors' view that the staic idea of anorexia nervosa as a unitary illness should be abandoned and replaced by a dynamic dimensional model according to which, in the course of time, changes may occur in the clinical picture of dysorectic patients.

A prospective study of tardive dyskinesia was carried out to gain information regarding the natural history of the condition and to identify risk factors. Out of an original cohort of 182 psychiatric patients receiving maintenance antipsychotic drugs 99 were available for reassessment after 3 years. In this follow-up group the point prevalence of oro-facial dyskinesia increased from 39% to 47% over the 3-year period. Twenty-two patients developed the disorder, while remission occurred in 14 others. Risk factors predicting the presence of oro-facial dyskinesia at follow-up included being over 50 years of age and the presence of akathisia. There was no convincing association between the duration of antipsychotic drug treatment and the presence or severity of oro-facial dyskinesia. Patients receiving over 1000mg chlorpromazine equivalents of antipsychotic drug per day were unlikely to have the condition. The amount of purposeless trunk and limb movement present proved to be a relatively stable phenomenon, showing only a slight increase with age and no change over the follow-up period. The implications of these findings are discussed, with particular consideration being given to the effects of loss of patients to follow-up.

On each of a sequence of trials subjects had to guess whether a cross would appear on the left or the right side of a computer screen. The sequence of cross positions was random. Normal controls, manic-depressive patients and patients with senile dementia produced relatively random sequences of responses, as did acute schizophrenic patients with positive symptoms. Acute schizophrenic patients with negative symptoms and chronic patients produced more stereotyped sequences with many response alternations (LRLR). Chronic schizophrenic patients with negative symptoms and intellectual deterioration (defect state) produced very stereotyped sequences with many preservations (LLLL). This severe restriction of response sequences is similar to that shown by animals after treatment with amphetamine. It is suggested that it is due to an impairment of a higher order control process which normally inhibits the repetition of sequences of behaviour when these have proved inappropriate.