Erythrocyte transketolase activation by thiamin diphosphate has been studied in elderly patients with moderate or severe chronic dementia, acute alcoholic admissions and chronic alcoholics with evidence of brain damage, mostly of the Wernicke–Korsakoff type. Significantly more patients in each group than controls showed abnormal activation of transketolase, not only by 0·3 mM thiamin diphosphate (TDP) but also in further activation by increase to 3 mM. This indicated the presence in a proportion of the alcoholic and the demented patients of an abnormal enzyme variant, similar to that previously found in vitro. The modified transketolase activation test may warn not only of marginal thiamin deficiency but also independently, of susceptibility to brain damage in patients at risk.

In three studies of comparable design, 47 schizophrenics received anticholinergic anti-Parkinsonism (AP) medications for two to four weeks along the course of neuroleptic treatment. Clinical ratings during the AP phase were contrasted against the preceding and following two-week periods on neuroleptic alone, and these changes were analysed for a total of 27 psychopathology dimensions and for clusters of seven positive and seven negative symptoms. Schizophrenics overall exhibited significant exacerbation of total psychopathology, and positive but not negative symptoms. Only those with a predominantly positive syndrome when drug-free were susceptible to AP therapeutic reversal. However, other subgroup analyses revealed worsening of total psychopathology and positive symptoms among catatonic, schizophreniform, chronic, and good outcome cases, but negative symptoms alone were significantly increased among paranoids. The results were not supportive of a positive–negative dichotomy of schizophrenia, but instead suggested a tripartite model: a distinct paranoid group and a division of the non-paranoids into a positive and a negative type.

The effect of diazepam on brain 5-HT-mediated neuroendocrine responses was studied in healthy male volunteers. An acute dose of diazepam (15 mg) significantly attenuated the prolactin and growth hormone responses to intravenous L-tryptophan. After 3 weeks administration of diazepam (25 mg/d) these responses had returned to normal despite much higher plasma diazepam concentrations, suggesting that tolerance had occurred. A reduction in brain 5-HT function may underlie some of the acute therapeutic actions of benzodiazepines. It is possible that excessive ‘rebound’ 5-HT activity may contribute to the abstinence syndrome seen on benzodiazepine withdrawal.

The psychobiology of anorexia nervosa is described and explained under four headings; (1) the psychopathology as related to the motivation for fasting; (2) metabolic and somatic consequences of starvation, including brain morphology; (3) endocrine abnormalities in the hypothalamic-pituitary-adrenal and gonadal axis; and (4) the hunger drive and its possible perversions in terms of aspects of neuroethology and the reward system in the brain.

In a sample of chronic schizophrenic patients, a group of symptoms which included poverty of speech and lack of spontaneous movement was found to be associated with poor performance in tests of conceptual thinking, object naming and long-term memory, and also with cortical neurological signs. A second group of symptoms which included formal thought disorder and inappropriate affect was associated with poor performance in tests of concentration, immediate recall and word learning, and with cortical neurological signs. The findings suggest that these two syndromes are associated with dysfunction at two different sites within the frontal lobes. A third group of symptoms, comprising various delusions and hallucinations, was associated with poor figure-ground perception, and might reflect temporal lobe dysfunction.

Urinary excretions of arginine vasopressin (AVP), sodium, potassium, osmoles and creatinine were measured in three in-patients with bipolar manic-depressive psychosis on at least eight 24-hour periods in each affective phase. Mood and body weight were recorded twice daily. The excretion by each patient of sodium, water and osmoles was greater in mania than during depression. Comparison of electrolytes and osmoles suggested that the increase was due to increased intake of salt and water rather than of total diet. There was a fall of mean AVP excretion during mania, the magnitude of the fall being related to the increase of water throughput.

Compared with controls, AVP excretion was high and variable. It did not show the normal relationship to urine osmolality. Days with very high AVP were not associated with any characteristic feature of the other measurements; nor were they confined to any one point in the manic-depressive cycle.

AVP does not appear to play a major role in the salt and water changes characteristic of manicdepressive psychosis and we have no evidence of its having any direct relationship to mood changes. We suggest that the observed abnormalities of AVP excretion are another manifestation of the central defect of this disease.

The hypothesis that ECT produces selective effects on hypothalamic–pituitary activity was investigated by determining the effect of ECT on pituitary hormone release in nine depressed patients. After ECT there were massive and rapid increases in the plasma concentrations of nicotine-and oestrogen-stimulated neurophysin (NSN and ESN), prolactin (PRL) and adrenocorticotropin (ACTH), smaller increases in plasma luteinizing hormone (LH) and cortisol, a significant decrease in plasma growth hormone (GH) concentration but no change in plasma thyrotropin (TSH). There was significant attenuation of PRL responses with repeated ECT. The hormonal responses to ECT cannot simply be attributed to stress, since a similar pattern of increases in plasma hormone concentrations did not occur in psychologically normal patients in whom plasma hormone concentrations were measured during induction of anaesthesia and abdominal incision for cholecystectomy. Analysis of these hormonal responses in terms of the knowledge available on the neurotransmitter control of pituitary hormone release suggests that some of these hormonal responses to ECT may be mediated by the activation of serotonergic neurones, while others are probadly due to direct stimulation of the neuroendocrine neurones themselves.

In order to ascertain the extent of hypothalamo-pituitary-adrenal cortical (HPA) hyperactivity in endogenous depression, we determined circadian serum cortisol patterns, cortisol responses to dexamethasone (DEX) administration, and urine free cortisol excretion before and after DEX administration in 40 definite endogenous depressives diagnosed with the Research Diagnostic Criteria. The cortisol measures ranged from normal to clearly elevated. To elucidate the clinical correlates of these hormone measures in the patients, we examined the relationships of the pre- and post-DEX cortisol measures to the diagnosis of endogenous/melancholic depression by different systems and to the overall severity and specific dimensions of depressive symptomatology.

In this group of endogenous depressives, none of the diagnostic schemes for endogenous/melancholic depression which we studied was significantly related to the pre- or post-DEX cortisol measures. Of the other subject and symptom variables, only age and the agitation/anxiety factor of the Hamilton depression scale showed consistent relationships with the cortisol measures. Both were positively correlated, to a moderate degree, with the hormone measures, and they were not correlated with each other. Together they explained approximately 20% of the variance in the cortisol measures. Thus, within a group of moderately to severely ill endogenous depressives, the older and the more agitated anxious patients have a significantly greater likelihood of showing increased HPA activity. These findings indicate that age should be controlled in studies of the HPA axis and that the subjective experience of anxiety may contribute to HPA hyperactivity in endogenous depression.

The effects of physostigmine on test performance of a patient with multiple cognitive deficits were observed in a double-blind, placebo-controlled study. Scores on tests of learning and memory and tests of visuo-spatial and constructional ability were both improved by physostigmine, while lecithin improved scores only on the former tests.

In 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Neuropsychological studies have shown that the integrity of the posterior corpus callosum is necessary for accurate colour naming in the left visual field (LVF) and colour matching across hemifields. Using this model, 22 schizophrenics, 14 depressive and 16 healthy matched controls were given a battery of tachistoscopic tests of colour perception. The schizophrenics made significantly more errors, in naming colours in the LVF compared to depressives, and in matching colours across fields compared to depressives and normals. There were no differences between groups for right visual (RVF) colour naming or matching within right and left visual fields. These findings support the hypothesis that trans-callosal transmission may be impaired in schizophrenia and are unlikely to be due to a specific disorder of colour perception, neuroleptic drugs or generally impaired performance. Those schizophrenics whose LVF naming errors exceeded RVF errors were more likely to have first rank symptoms and showed less cerebral atrophy but did not differ on other variables. The techniques described may be useful for further research into interhemispheric function in schizophrenia.

Effective community treatment of schizophrenia involves not merely the removal of florid symptoms, but restoration of effective social role functioning. The efficacy of a family management approach is compared with an individual approach of similar intensity in terms of its impact on the patient's social adjustment after a florid episode of schizophrenia. Clinical reports, patient self-reports, and interviews with the family members of 36 patients, who were randomly assigned to family or individual management, demonstrated a consistent superiority for family management. The advantages for the family approach were sustained over a two-year period. The potential mechanisms through which the family approach may have achieved its greater efficacy are discussed from a multi-determined perspective.

The CNS maintains a fundamental distinction between actions elicited by external stimuli and actions elicited by internal goals (acts of will). As a result the intact organism can monitor centrally three aspects of its own actions: (1) the action appropriate to current external stimulation (stimulus intention or meaning); (2) the action appropriate to current goals (willed intention); and (3) the action which was actually selected (corollary discharge). In Type I (acute) schizophrenic patients, intentions of will lead to actions, but these willed intentions are not monitored correctly. This apparent discrepancy between will and action gives rise to experiential (1st rank) positive symptoms (e.g. delusions of control and passivity). In Type II (chronic) patients, intentions of will are no longer properly formed and so actions are rarely elicited via this route. This gives rise to behavioural negative signs (e.g. poverty of speech).

The behaviour of Type II schizophrenics has surface similarities to that shown by patients with Parkinson's disease and patients with frontal lobe lesions in that all three types of patient show a relative deficit of actions elicited by willed intentions. Dopamine blocking drugs reduce positive symptoms in Type I patients precisely because they induce Parkinsonism, i.e. reduce the likelihood of actions being initiated by willed intentions. This in turn reduces the likelihood that actions will occur for which the patient had no awareness of his intention to act.

The vasopressin analogue 1-desamino-8-D-arginine vasopressin (DDAVP) has been shown in healthy male volunteers to cause significant improvement in short-term memory and to reduce alcohol-induced amnesia. There was no significant effect upon semantic retrieval or simple reaction time. It was concluded that vasopressin benefited the initial processes of consolidation and learning, while the reduction of the amnesic effects of alcohol may support the contentions of other authors that the peptide improves memory in states of mild amnesia.

This paper describes research which sought to investigate and describe the interpersonal relationships and vulnerability to psychiatric disturbance in severely closed head injured subjects. The head injured subjects were severely injured, with mild or extremely severely injured individuals being excluded from this study. Self-report by the injured individual was compared with relatives' reports. Fifteen head injured people were individually matched with non-head injured people from the general population who acted as controls. Each subject nominated one ‘close other’ for comparative interview. The dependent variables included interpersonal relationships, non-psychotic psychiatric disturbance and behavioural change.

The head injured group differed significantly from the control group in the quantity of interaction but not in the perceived quality of interaction. The groups differed significantly on behavioural change. No significant difference was found between responses given by the head injured and their ‘close other’ compared with the controls. Deficient quantity of interpersonal relationships and greater vulnerability to psychiatric disorders was shown in this sample. Further research on the assessment of long-term social outcome and psychiatric stability in the head injured could assist in the improved long-term rehabilitation of the survivors.

Platelet-rich plasma from healthy controls was pre-treated with neuroleptics of the phenothiazine, butyrophenone or benzamide variety before aggregation with one of the following agonist agents: ADP, adrenaline, 5-HT, collagen, platelet activating factor or ristocetin. All compounds effective as antipsychotics, except sulpiride, depressed aggregation. Unmedicated schizophrenics showed aggregation responses indistinguishable from healthy controls. However, within days of treatment with either trifluoroperazine or haloperidol responses became abnormal in acutely psychotic patients. Increased responses to 5-HT and depressed responses to platelet activating factor were detected. After 4 weeks of treatment responses tended to return to normal. Aggregation responses were normal in those patients on long-term depot neuroleptics.

The principle of distinguishing between selective memory deterioration and global intellectual decline has been applied to 38 patients with alcoholic Korsakoff's syndrome. Indices were developed for each type of deficit and their distributions explored. Considerable variation was seen in both parameters, the transition from pure memory loss to global intellectual deficits appearing to be gradual. Differences were found in the sex and CT scan associations of the indices. The implications of the distinction for future research are discussed.

The relationship between memory performance and CT scan measures of ventricular size was investigated in a sample of 39 chronic alcoholics and 39 controls. Measures of verbal, non-verbal, recognition and recall memory were derived from the tests administered and were viewed in relation to the lateral ventricle and third ventricular size measurements. The results showed that the memory performance of male alcoholics was significantly related to measures of third ventricular size, but probably not to measures of the lateral ventricles. An association between verbal memory performance and CT scan measures was found in the male controls.

Using the family history method, we assessed the morbid risk for psychiatric disorders the first-degree relatives of 69 probands with bulimia, 24 probands with major depression, and nonpsychiatric control probands. The morbid risk for major affective disorder among the first-degree relatives of the bulimic probands was 32%, significantly greater than that found in the nonpsychiatric control probands. The rate of familial major affective disorder was significantly greater in bulimic probands who had a history of major affective disorder themselves than in bulimic probands without such a history - but the latter group, in turn, displayed significantly higher rates than the nonpsychiatric control probands. Eating disorders were slightly, but not significantly, more prevalent in the families of bulimic probands than nonpsychiatric control probands. We present two alternative hypotheses which might explain these findings.

Five idiots savants whose artistic output was judged to be at art school entrance standard were matched for performance and verbal IQ with control subjects who had no special artistic talent. Each subject was given tests of reproductive skill with both concrete pictures and unfamiliar and unnameable geometric designs. They were also asked to draw a man, and a test of picture completion was given which involved constructive imagination. In all tests the idiots savants proved clearly superior to IQ-matched controls, indicating the presence of an IQ-independent talent. The results are interpreted in terms of a superior image memory and ready access to a ‘picture lexicon’. In addition, the existence of superior graphically directed motor programmes must be assumed.