The mean index episode length in 19 consecutive admissions with treatment-resistant bipolar affective disorder was 21.7 months. Four patterns of resistance were identified: rapid cycling (37%), other forms of cycling (32%), chronic depression (26%) and mixed states (6%). Female gender was significantly associated with rapid cycling. Other risk factors for treatment-resistant bipolar disorder, including a high prevalence of family history of affective disorder (72%) and electroencephalographic abnormalities (54% of recordings), were not confined to the rapid cycling group.

Four cases of lithium-induced neurotoxicity are presented which, taken with evidence from previous reports, indicate that specific risk factors for lithium-induced neurotoxicity at normal serum levels are rapid dosage regimes, concomitant neuroleptic therapy, pre-existing EEG abnormalities, undetected cerebral pathology, organic impairment, and genetic susceptibility.

Fifty-five patients with primary major depression were followed up prospectively from time of onset of the index illness episode until recovery. The course of depression in hospital-treated patients was protracted, with a median length of episode of one year. Two factors significantly predicted persistence of symptoms: interval between onset and receipt of treatment, and premorbid neuroticism, which accounted for 55% of the variance in length of episode.

This short review outlines the clinical profile of the selective serotonin re-uptake inhibitors (SSRIs). There has been much recent publicity and promotion of this group of drugs and this review attempts to give a balanced account of their current place in the treatment of depression. Although a large number of preclinical and clinical trials have been carried out many questions and problems remain – it is important to proceed carefully and carry out (and replicate) controlled independent clinical trials. The views of general psychiatrists and GPs about these drugs in normal clinical practice will be the acid test – this will be particularly important in view of their cost.

Our study of chronic and non-chronic depressive patients suggests that the following individual factors may predispose a patient to develop chronicity: unipolar depression, neurotic premorbid personality, high familial loading for affective disorder and multiple life events before and after the onset of the illness episode. It is interesting to note that bipolar disorders appear to be under-represented. This may be due to symptomatic chronicity in bipolar illness being more often represented by rapid cycling disorder.Evidence from a group of prospectively ascertained depressives with a median duration of illness of one year showed that apparently 75% of the variance in length of illness episode can be explained. Thus time taken to introduce active treatments, premorbid neuroticism, the occurrence of life events before and after the onset of illness, age at onset of first illness episode and family history of affective disorders were confirmed as important predictor variables. The fact that 85% of patients who develop chronic primary major depressive disorders have previously had an episode of affective illness tends to militate against the stereotype of these patients having a personality disorder.In future, it is important that biological research (for example, neuroendocrine studies) is directed towards chronically depressed patients. In the past, these patients have tended to be excluded from such studies as they represent an atypical population. It is therefore quite clear that future research should be directed towards not only pharmacological but also psychological and social mechanisms which lead to the perpetuation of depressive illness.

SUMMARY N ‐pro‐opiomelanocortin ( N ‐POMC) is secreted from the same precursor as ACTH and β‐endorphin. Elevated plasma ACTH and β‐endorphin β‐lipotro‐phin concentrations have been reported in depression, however there have been no previous studies of N ‐POMC. Twenty‐five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N ‐POMC was measured using a newly developed two‐site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N ‐POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N ‐POMC at 0900 h post‐dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC‐derived peptides. N ‐POMC has a similar pattern of abnormal concentrations to ACTH and β‐endorphin /β‐Iipotrophin in depression. This constitutes probable evidence of POMC‐derived peptide resistance to glucocorticoid feedback in this condition.

Post-mortem brain tissue was obtained from a group of patients with well documented clinical histories of affective disorder. 5-Hydroxytryptamine-1 (5-HT1) and 5-HT2 receptor binding to homogenates of frontal cortex (Brodmann area 10) was measured using tritiated 5-HT and tritiated ketanserin respectively. 5-Hydroxyindoleacetic acid (5-HIAA) levels from the same brain samples were measured by reverse-phase high performance liquid chromatography with electrochemical detection. A tendency towards increased 5-HT receptor binding density in patients with major affective disorder was found compared to dysthymic disorder patients and normal controls. No relationship was found between receptor binding densities and metabolite values, nor were the differences in 5-HT binding correlated with time to autopsy, storage time prior to assay, or to clinical variables including DSM-III psychoticism/non-psychoticism and melancholia. Previous antidepressant drug histories were similar in the two patient groups and are unlikely to account for the findings. An increase in postsynaptic 5-HT2 receptor binding in major affective disorder is a possible pathophysiological mechanism which is compatible with the observed down-regulatory effect of antidepressant drugs (although not electroconvulsive therapy) on 5-HT2 sites. The methodological problems inherent in post-mortem studies in affective disorder are discussed.