Serotonergic anorectics are correctly defined only if they enhance 5-HT transmission and have their anorectic effects inhibited by drugs that block 5-HT receptors. Fenfluramine, the prototype indirect 5-HT agonist, and its metabolite, norfenfluramine, act as 5-HT releasers and uptake inhibitors and are both more effective in the dextro form. They lack the stimulant activity and do not cause hyperthermia or stereotypical behaviour as is characteristic of amphetamines. The anorectic effect of those drugs is attenuated by metergoline, a 5-HT receptor antagonist, in animals and man; 5-HT uptake inhibitors such as fluoxetine, zimelidine, SL 810385, and sertraline also cause anorexia, but only sertraline antagonism by metergoline has been reported. The effect of serotonergic anorectics on 5-HT release has been poorly investigated. Quipazine and RU-24969 cause anorexia by acting directly on 5-HT post-synaptic receptors. Serotonergic nerve terminals take up [3H]-D-fenfluramine and bind with high affinity in rat brain; uptake, an active process, appears to occur at a different site than binding, which is not affected by ouabain or low temperature. Anorexia is probably induced by interaction with 5-HT1B receptors in the rat; the human equivalent of this receptor is not known, but the 5-HT1D type is a likely candidate.

The two-syndrome concept of schizophrenia was investigated in a sample of 70 Nigerian schizophrenic patients. The positive and negative syndromes were studied in relation to demographic, historical, neurological and psychometric measures. The negative syndrome was associated with cognitive impairment, behavioural deterioration and left eye dominance, and also with poor pre-morbid educational achievement and longer length of current stay in hospital. The positive syndrome was unrelated to any of the independent variables. The two syndromes were not significantly related, supporting the view that they represent relatively independent dimensions of pathology. This provides further support for the validity of the Type I–Type II subtyping of schizophrenia in populations of patients from different cultural backgrounds, and suggests that the negative syndrome is related to the presence of neurodevelopmental deficits that possibly antedate the schizophrenic illness.

A total of 101 elderly depressed patients and 85 community residents (matched for age and sex) were interviewed about life events, difficulties, and confiding relationships. Significantly more of the depressed sample reported at least one severe event in the three months before the onset of their illness. Lack of a good confiding relationship was associated with depression in men but not in women. In this relatively affluent Australian sample, life difficulties were rare and, probably as a result, were not significantly associated with depression.

The fit of the structure of DSM–III major depressive disorder to data from two large epidemiological surveys is assessed by latent class analysis. The surveys were conducted at the Baltimore and Raleigh–Durham sites of the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program. Three classes are required to fit the data, and the third class bears a strong resemblance to major depressive disorder, although it requires slightly more symptoms to be present than DSM–III. The derived structure replicates successfully for Baltimore and Raleigh-Durham, with a prevalence of the major depression category of 0.9% for both sites.

The hypertensive crisis induced by the ingestion of cheese in subjects undergoing treatment with monoamine oxidase inhibitors (MAOIs) led to their virtual disappearance in many parts of the world. Three strategies to try and diminish the risk of this reaction have been developed: the combination of current (irreversible and non-selective) MAOIs with tricyclic antidepressants, the use of new selective MAOIs, and the use of new reversible MAOIs. The relative effectiveness of these different approaches can be assessed by the tyramine pressor test. The introduction of reversible and selective monoamine oxidase-A (MAO-A) inhibitors looks especially promising clinically.

The sensitivity of the GHQ and a revised scoring procedure (CGHQ) for chronic psychiatric complaints was investigated on 175 outpatients. The mean level of severity of symptoms of the groups with and without chronic complaints was not significantly different. However, patients with chronic complaints showed a significantly lower mean GHQ score than patients without chronic complaints. The mean CGHQ scores of the two groups did not differ, suggesting that the CGHQ is a better indicator of the severity of the chronic psychiatric state than the GHQ. The revised scoring procedure resulted in a decrease in the number of false negatives. The strongest reduction in false negatives, however, was induced by a combination of the original and the revised scoring procedures. This reduction was achieved at the expense of only a small increase in the number of false positives. Altogether, the revised scoring procedure proved to be only marginally better.

Urinary 6-sulphatoxymelatonin (αMT6s) excretion was measured after one day and one, two and three weeks of desipramine treatment in eight depressed patients. There was a significant increase in the urinary excretion of αMT6s after one week of treatment, and at no time was there any decrease in αMT6s excretion. These findings are opposed to the hypothesis that desipramine reduces noradrenergic neurotransmission in the human pineal. In a further five patients whose depression was resistant to desipramine alone, urinary αMT6s excretion was measured during treatment with adjunctive L-triiodothyronine (T3). There was no change in αMT6s excretion, and thus the previously reported potentiation of the efficacy of tricyclic antidepressants in combination with T3 does not appear to be mediated through an alteration in noradrenergic neurotransmission.

Rating scales for negative symptoms, basic symptoms and other comparable psychopathological syndromes were not originally constructed in order to make psychiatric diagnoses. Moreover, these scales were intended to be applied principally to schizophrenic patients. From the point of view of psychological testing their application to non-schizophrenic patients could be rejected on methodological grounds. Nevertheless there are some considerations which may justify such an investigation.

The pharmacotherapy of psychotic disorders which started in 1952, based on empirical results obtained with chlorpromazine by Delay & Deniker, has revolutionised the treatment of psychiatric diseases of non-organic origin. The discovery of haloperidol by Janssen in 1959 represented further progress in this field, since this was found to be more potent and to have generally less disturbing adverse effects than chlorpromazine. Nevertheless it took several years before dopamine-antagonism was put forward as possible mechanism of action for neuroleptic drugs (Carlsson & Lindqvist, 1963). From the early 1970s, however, the advent of radioligand binding studies provided new tools for studying neurotransmitter receptors in the brain and for investigating the interaction of drugs with various receptors. This technique allowed identification of receptor-binding sites related to pharmacologically defined receptors and receptor subtypes, e.g. α and β-adrenergic receptors. It also led to further subclassification and refined definition of receptors, e.g. dopamine-D1 and -D2, and different pharmacological effects mediated by the receptor subtypes have been identified.

Depression, anxiety and psychomotor performance were assessed in 20 depressed patients during double-blind treatment with amitriptyline or trazodone. There was no difference in onset of antidepressant or anxiolytic action. No decrement or improvement on computerised tasks was found. Dry mouth was significantly more frequent and severe with amitriptyline.

Hypotheses as to the pathogenesis of schizophrenia can be discussed at different levels of a possible manifestation of the causative factor: the macroscopic-morphological, the microscopic-morphological, and the molecular. Some abnormalities have been observed on all of them: e.g. increased ventricular-brain ratios in CT, hypofrontality in SPECT and in glucographic PET-scans, and other macromorphological abnormalities (for reviews cf. Bogerts 1984; Mundt, 1986; Bogerts et al, 1987), gliosis on a microscopic level (Stevens, 1982), and an increased dopamine-binding in in vivo receptor studies (PET as well as in post-mortem studies; Cazzullo, 1988). However, the diversity and variability of these findings point to the view that rather than there being a single distinct pathogenetic factor responsible for the pathogenesis of schizophrenic psychoses, a constitutional disposition exists, which can be described as a functional dysequilibrium within the human brain. From this point of view, schizophrenia would not appear as an inherited disorder of metabolism, but as a weakness of a neurobiological ‘system’, i.e. as an interactional disorder of a complex of networks, in which the interaction between different substructures is labile in such a way that under special conditions (e.g. ‘stress’), a decompensation (functional breakdown) results. In this sense, ‘vulnerability’ to schizophrenia may be interpreted as a consequence of a constitutional deficiency of the brain which results in an inability to stabilise, under specially challenging conditions, the interaction between different substructures of the human brain. Before this ‘functional dysequilibrium-hypothesis’ (which is a special form of a constitutional structural deficiency-hypothesis) is discussed, and before the question is raised as to which are the relevant dysequilibrated components, some indication will be given as to why such an hypothesis appears plausible.

These three papers by psychiatrists from the German-speaking world all deal mainly with the nature and aetiological basis of the psychological deficits manifest as ‘negative’ symptoms in schizophrenic illness. There is just an echo of the controversies regarding the validity of subdivision of schizophrenia into ‘positive’ and ‘negative’ forms that have received much attention from British and North American psychiatrists in recent years. (Andreasen et al, 1982; Crow, 1985). It appears to be implicitly assumed that schizophrenia is a unity. The acute psychoses which are diagnosed as schizophrenic in most countries but named ‘psychogenic psychoses’ in Scandinavia and ‘bouffée delirante’ in France and ‘emotion psychoses’ in Switzerland (Labhardt, 1963) are not allowed to complicate matters.

In double-blind sequential study, diazepam was compared with the proven antidepressant moclobemide, in patients with atypical depression. Both agents significantly improved depression ratings over eight weeks of treatment. Diazepam was a significantly better antidepressant than moclobemide at four weeks, although not at eight weeks. All patients ceased diazepam within one year and none reported withdrawal reactions. These data suggest the need to reconsider that benzodiazepines may be antidepressants and to study their possible antidepressant actions.

Psychotropic drug use was investigated using a two-stage survey of a random sample of persons aged 17 and over from a rural Spanish community. It was found that 6.9%, 11.8% and 25.1% of the population were consuming psychotropic, analgesic and somatic medicines respectively. Women presented a higher rate of psychotropic use than men (prevalence for women 10.7%, for men 2.6%). This female predominance was found to be significantly related to sociodemographic and medical factors. Psychotropic use was also associated with the physical health of the respondent. The coexistence of physical and mental illness generated an increase of consumption, whereas the absence of both types of illness was associated with a very low rate. The rates for physical and for mental illness alone were intermediate and were almost equal.

The cheese reaction following use of the irreversible monoamine oxidase inhibitors (MAOIs) began to be reported in the UK with increasing frequency from about 1961. By 1965, the underlying mechanism (tyramine-provoked hypertension) had been essentially elucidated. Thereafter, this potentially severe side-effect could have been largely avoided by the use of fairly simple dietary precautions. Unfortunately, suspicion and fear burgeoned, and both the seriousness and the frequency of risk were dramatically inflated. This was a major factor in the subsequent general disuse of the irreversible MAOIs. Second-generation MAOIs which are selective for monoamine oxidase-A and B are now being synthesised and may eliminate the eventuality of hypertension without special dietary precautions.

Forty patients under the age of 60 years with a DSM–III diagnosis of bipolar affective disorder were examined for the presence of tardive dyskinesia. The overall prevalence was 22.5%, with an age-related increase. Patients with and without tardive dyskinesia did not differ in terms of duration of affective illness or exposure to neuroleptics, but those patients with tardive dyskinesia had significantly more psychiatric admissions and were on lithium for significantly greater lengths of time.

It has been argued that school refusal may not be a unitary syndrome, but a common presenting symptom founded on differing underlying dynamics. The paper explores this hypothesis empirically. The clinical files of 100 refusers were scored for several variables which could potentially differentiate between school refusal subtypes, and for several commonly accepted beliefs about school refusal. The data were subjected to a variety of analyses, culminating in cluster analysis. Cluster (C) 1 consisted of children who feared separation from dependent, overprotective mothers. C2 youngsters were perfectionistic and depressed. They dominated mothers who had been deprived in childhood. C3 consisted of extensively disturbed children from multiproblem families, who had suffered early separation or loss, and who were fearful and depressed.

The role of central serotonergic (5-HT) system dysfunction in the regulation of aggression in both animals and man has been investigated for more than the past two decades. Evidence for reduced central 5-HT in the mediation of aggression comes from both behavioural and correlative studies. Functional reduction and augmentation of 5-HT activity is respectively associated with increased and decreased aggression in various animal models of aggression. While similar studies in man have not been performed, strong and consistent associations between indices reflecting reduced pre-synaptic 5-HT activity and aggression have been reported. Evidence of post-synaptic receptor upregulation in the brains of suicide victims has also been reported leaving the functional status 5-HT activity in such patients an open question. However, reduced neuroendocrine (i.e. prolactin) responses to fenfluramine, a 5-HT uptake inhibitor/releaser, which activates both pre- and post-synaptic sides of the 5-HT synapse, strongly suggest that overall central 5-HT activity is reduced in mood and/or personality disorder patients with history of suicidal and/or impulsive aggressive behaviour. Preliminary data with the 5-HT receptor agonist m-chlorophenylpiperazine further suggest that reduced activity of post-synaptic 5-HT receptors may be an important correlate of impulsive aggressive behaviour. Pharmacological agents with potent 5-HT pre- and/or post-synaptic augmenting effects should be tested clinically to determine their efficacy in the treatment of impulsive aggressive behaviour in psychiatric patients.

Patients aged 18–64 years, in hospital more than one but less than six years, were followed up five years after identification: 22% had died, 50% remained in-patients, and 28% had been discharged; only 10% of first admissions with organic brain disease had left hospital. Of those discharged, 37% had no contact with after-care services. Of those remaining in hospital, 39% did not require in-patient care. Patients' level of functioning had improved over the five years.

To investigate the relationships between the immune apparatus, major depression, and HPA-axis and noradrenergic activity, the authors measured the lymphocyte stimulation responses to the mitogens phytohaemagglutinin (PHA), pokeweed mitogen (PWM) and concanavalin A (CON A), post-dexamethasone Cortisol (DST) values and 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion in 24-hour urine samples from 48 patients. We found that lymphocyte responses to PHA and PWM in melancholic and psychotic depressives were significantly lower than in minor depressives. The lymphocyte responses to PHA, PWM and CON A showed significantly negative correlations with age, DST results and HRSD score. Responses to PHA were significantly negatively correlated with MHPG excretion. Up to ±33% of the variance in the three mitogenic lymphocyte responses could be explained by canonical correlation with age, DST results and MHPG values.