Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.

Few psychiatric disorders have yet been adequately validated and it is still an open issue whether there are genuine boundaries between the clinical syndromes recognized in contemporary classifications, or between these syndromes and normality. In the long run validation depends on the elucidation of aetiological processes. There are, however, a number of strategies which clinicians could use, but at present rarely do, in order to improve and validate existing classifications. Most of these involve studying populations which have been deliberately chosen to represent a broader grouping than a single diagnostic category, or even a group of related categories.

It has been my custom as Head of the Department of Psychiatry at Washington University to interview as many as possible of the medical students applying for positions in our residency training programme. I typically ask the candidates how they decided to apply to us, what they know about our programme, and what they have heard from others about our department. The answers to these questions have been interesting and informative to me and have characteristically provided a good basis for the discussions that followed, designed to help us decide about the applicants and, equally important, to help the applicants decide about us.

Ten patients with seasonal affective disorder received the following treatments for 5 days each: (a) artificial daylight (2500 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (b) red light (300 lux) from 20.00 to 23.00 and from 07.00 to 10.00 hours; (c) artificial daylight (2500 lux) from 22.00 to 23.00 and from 07.00 to 08.00 hours. The antidepressant effect of treatment (a) was superior to that of treatment (b), suggesting that the effect of light treatment in winter depression is more than that of a placebo. The antidepressant effect of treatment (a) was superior to that of treatment (c), although these two treatments equally suppressed plasma melatonin concentrations. Consequently, in these patients there is a dissociation between the effect of light treatment on melatonin and the reduction of depression ratings.

The secretion of prolactin and growth hormone (GH), together with subjective ratings of sedation and hunger, were determined in 13 in-patients with anorexia nervosa and 15 controls during the intravenous infusion of L-tryptophan (100 mg/kg). Prolactin responses were not different between groups but GH responses were markedly blunted in patients. In addition sedation responses in patients were attenuated compared with controls. Hunger ratings were reduced by the infusion in controls but were too variable to be interpreted in the patients. Plasma amino acid levels were also determined before and after infusion of L-tryptophan. Tryptophan levels were comparable in the two groups as were the levels of tyrosine, phenyl alanine, valine, leucine and iso-leucine. The results suggest that some aspects of 5-hydroxytryptamine function may be attenuated in anorexia nervosa. However, they undoubtedly contrast with the finding of enhanced hormonal responses in acute dieting and may be relevant to the interpretation of similar experiments in depressive illness.

There has been concern about whether standardized psychiatric interviews make valid diagnoses. Agreements between the Diagnostic Interview Schedule (DIS), as an example of a standardized interview, with independent assessments by a clinician are reasonably high in most studies, but the clinical assessment is itself of uncertain validity. Using predictive ability is an alternative way of judging validity. Data are presented to show that the DIS is almost as good at prediction as a clinician's assessment, but here too there are problems. Because prediction is probabilistic (i.e. the same disorder can have multiple outcomes, and different disorders can share outcomes), it is not possible to say how good prediction has to be to demonstrate perfect validity.

Across varied methods of validity assessment, some disorders are regularly found more validly diagnosed than others, suggesting that part of the source of invalidity lies in the diagnostic grammar of the systems whose criteria standardized interviews evaluate. Sources of invalidity inherent in the content and structure of a variety of diagnoses in DSM-III and its heir, DSM-III-R, are reviewed and illustrated, in part with results from the Epidemiological Catchment Area study.

The relationship between diagnostic criteria and standardized interviews is symbiotic. While attempts to adhere closely to existing diagnostic criteria contribute to the diagnostic accuracy of standardized interviews, the exercise of translating official diagnostic criteria into standardized questions highlights problems in the system's diagnostic grammar, enabling standardized interviews to contribute to improvements in diagnostic nosology.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia or neurological disease (Huntington's disease) which had been found to induce a cytopathic effect (CPE) in human embryonic fibroblast cell culture was injected intracerebrally into common marmosets. Behavioural observations were made on the animals during a period of 2½ years prior to injection and for 2½ years after injection. In an earlier study (Baker et al. 1983 b) we found that animals injected with CPE + ve CSF became progressively more inactive when compared with those injected with non-cytopathic (CPE – ve) CSF from control patients. In the present study we were unable to replicate this finding. No difference in behaviour emerged between animals injected with control CSF and animals injected with CSF from schizophrenics or patients with neurological disease, nor between animals injected with CPE + ve CSF and animals injected with CPE – ve CSF. The numbers of offspring produced and surviving did not differ between the groups. We conclude that the original findings were due to factors unconnected with the nature of the injected material.

Evidence is presented here in support of the efficacy of carbamazepine (CBZ) in a variety of different psychiatric conditions. While there is now considerable evidence to support the use of CBZ in the acute treatment of mania and in the prophylaxis of bipolar affective disorder, particularly as a second-line drug, its usefulness in other conditions is less well documented. Overactivity, aggression and poor impulse control appear to improve in a variety of different diagnostic categories, and it may possibly be more appropriately prescribed to control or prevent these symptoms than as a treatment for a particular disease entity. The use of CBZ as an antidepressant is not well proven. Most of the adverse effects reported are due to rapid initial escalation of dosage, which can be avoided, or are reversible such as drug rashes. Severe adverse effects have been reported but are rare. Frequent monitoring of drug plasma concentration is not required. Some reports of synergism with lithium have appeared and combination therapy may be a useful strategy. Drug interactions, the need for clinical monitoring, and the possible pharmacological mode of action of CBZ are also discussed.

The endocrine responses to Luteinizing Hormone Releasing Hormone (LHRH) of eight drug-free males with mania were determined. Basal levels of Luteinizing Hormone (LH) and the plasma levels following injection of LHRH were elevated in patients compared with controls; Follicle Stimulating Hormone (FSH) and testosterone were not different. Elevated levels of LH have been described previously in recovered manic patients and have been suggested to be state-independent features of mania. In order to clarify the status of this finding, the effects of lithium administration upon hormone responses to LHRH in six male volunteers were also investigated, together with the effects upon Thyrotrophin Releasing Hormone (TRH) stimulation of Thyroid Stimulating Hormone (TSH) and prolactin release. Lithium increased the basal levels of LH and levels after injection of LHRH without effect upon FSH and testosterone. Lithium also increased basal and TRH stimulated release of TSH and basal prolactin levels. Lithium was without effect upon prolactin responses to TRH. The results are discussed in relation to current information on the mechanism of lithium's action. The implications for neuroendocrine work on recovered patients taking lithium are also explored.

A wide range of abnormalities of the hypothalamo-pituitary-adrenal (HPA) axis has been described in depression. This paper reviews recent advances in the understanding of this system, and draws them together to construct a model for the purposes of further research and discussion. It is proposed that there are two fundamental changes which both originate in the hypothalamus: an increased secretion of corticotropin-releasing hormone, and a neurally mediated adrenal hyper-responsivity to ACTH. The resulting changes in hormone regulation would be expected to produce all the characteristic HPA axis abnormalities commonly seen in depression. The model makes several predictions which could be tested by future experiment.

Three variants of a simple reaction time task with regular and irregular series of different preparatory intervals (Pls) were presented to schizophrenics and a control group of alcoholics and normals: the visual warning signal (WS) either (1) remained fixed, (2) shrank at a constant rate, or (3) changed in size erratically. Time information provided by shrinking WSs reduced the average reaction time in all groups and attenuated the crossover effect (COE) of schizophrenics, although even here more schizophrenics than controls had COE-scores ≥ 25 msec. Erratically changing WSs introduced the COE in controls. Within groups the COE was not related to general response speed, age, duration of hospitalization, or medication. Results are interpreted as indicating that schizophrenics eschew controlled anticipatory processes on the basis of WS- and PI-information which are crucial for motor preparation when PIs are too long to allow an automatic perceptual grouping of warning and imperative stimulus. This may also occur in controls when time estimation is impeded by distraction.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for 67 elderly patients who met the DSM-III criteria for delirium and for 19 age-matched controls. As a group, and also when subdivided according to the type of delirium, severity of cognitive decline or the type of central nervous system disease, the delirious patients showed significant reductions of SLI compared with the controls, together with a declining trend associated with increasing cognitive dysfunction. These findings are in accordance with previous observations that reduced CSF SLI is associated with diseases in which cognitive function is disturbed and they extend this finding to delirium.

Three studies examine the role that provocative visual stimuli have in eliciting anxiety reactions in people with agoraphobia. Such stimuli elicit more anxiety in agoraphobic patients than control subjects. The effect of visual stimulation appears to be specific: (1) non-visual stimulation is without comparable effect; (2) both control and agoraphobic groups show similar effects of visual stimulation on another reaction such as headache. The anxiety effects of visual stimuli are correlated with the extent to which subjects experience depersonalization and somatic symptoms of agoraphobia, but not correlated with depression or the behavioural or cognitive aspects of agoraphobia. Alternative accounts of the possible role of visual stimulation in the anxiety reactions of agoraphobic patients are discussed.

The present study, using a diathesis-stress model, attempted to confirm prior findings with platelet monoamine oxidase (MAO) activity and stress in a middle-aged, non-clinic population. One hundred and seventy-eight adult males from a statewide community club were tested for platelet MAO activity and stressful life events and were also given a variety of psychological measures of both psychopathology and psychosocial coping. The data were examined both for correlations across the total sample and for a comparison of high-risk groups (top and bottom 15% of MAO activity) with a middle MAO group. Low platelet MAO activity was related to a higher incidence of contact with mental health professionals, and more frequent use of alcohol and cigarette smoking. High MAO activity was related to higher levels of anxiety and somatization. High levels of stress were related to increased psychosocial problems reported for female and family members, higher scores on two schizophrenia-related MMPI scales (schizophrenia and paranoia subscales), but fewer idiosyncratic associations, elevated hypomanic, depression, and anxiety scores, increased alcohol use, and increased use of prescribed antianxiety and sedative medication. Neither MAO nor stress were related to current levels of psychosocial coping. Moreover, no interaction effects were uncovered for MAO activity and stress combined.

Twenty-seven chronic schizophrenics and nineteen controls, all male, were evaluated by computed tomography (CT) scans. Lateral, third and fourth ventricles and cerebral density numbers were measured. In the schizophrenic patients there was a significant increase in third ventricle width. Ventricular Brain Ratio (VBR) and there were significantly higher densities of white matter in the right frontal and parietal region.

Thirty (33%) of 90 patients with the Gilles de la Tourette syndrome exhibited selfinjurious behaviour. Fourteen were head bangers, of whom two had cavum septum pellucidum. Clinical correlates of self-injury were the severity of Gilles de la Tourette syndrome symptoms and psychopathology, with special reference to obsessionality and hostility. We discuss an additional patient who died from a subdural haematoma as a result of head banging, and three who had permanent vision impairment from self inflicted eye injuries.

Repetition of other person's activities is, to some extent, part of normal human behaviour. However, in some circumstances it becomes pathological and symptomatic of an underlying disease process. The pathogenesis of this type of behaviour is very diverse. The circumstances in which echoing can be expected to occur are reviewed.

Two hundred and eighty-four male college volunteers were screened for smooth pursuit eyetracking deficiencies, a commonly reported concomitant of schizophrenia. A sample of 36 subjects, weighted with poor eyetrackers, was brought into the National Institute of Mental Health laboratory and retested on electro-oculogram and infrared tracking procedures. They were also administered psychological tests which assessed nine dimensions relevant to schizophrenic, neuropsychological, and affective disorders. In the area of schizophrenia-like symptoms, measures of attention deficits, stimulation avoidance, and identity problems predicted poor eyetracking for the whole sample. Using the poor eyetracking subjects alone (N = 24), interpersonal withdrawal was also significantly related to poor performance but not stimulation avoidance. In the neuropsychological area, measures of attention control and perceptual-motor dysfunction for the total sample, and perceptual problems and general intellectual decrements for the poor eyetrackers were significantly related to poor performance. There was no relationship between measures of affective dysfunction and poor eyetracking.

This study reports the psychiatric morbidity in 116 patients with definite multiple sclerosis (MS). The presence of brain pathology was investigated using magnetic resonance imaging (MRI). A group of 48 physically disabled controls suffering from rheumatic or neurological conditions not involving the brain was used for comparison. Normative MRI data were obtained from a group of 40 healthy volunteers.

Psychiatric morbidity was significantly higher in the MS group with nearly half of the patients scoring as cases at interview. There was no evidence to suggest that psychiatric symptoms in isolation were the first manifestation of MS in the present material. The presence of psychiatric illness at interview was significantly related to the degree of social stress as perceived by the patient. The severity of MRI abnormalities was greater in those with longer histories and greater physical disability, but did not show a significant relationship with global measures of psychiatric disability. Of the various psychiatric symptoms elation was significantly correlated with the presence of widespread MRI abnormalities, while flattening of affect, delusions and thought disorder correlated with the degree of pathology in the temporo-parietal region.

A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P < 0·01) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen.

The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.