One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side-effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia.

Animal behavioural models of psychiatric disorders cannot exactly simulate human psychopathology, but they can be used to evaluate the behavioural changes induced by drugs and to suggest hypotheses about the functions of the CNS and its involvement in psychiatric disorders. This should lead to a more heuristic classification of psychotropic drugs and to clarification of their therapeutic possibilities. The following animal models simulate aspects of depressive disorders and are sensitive to the antidepressant effects of drugs. (i) The forced swimming test: described as ‘behavioural despair‘ on the assumption that the animal has given up hope of escaping. (ii) The ‘restraint stress‘ test: this may indicate a failure to adapt to stress. (iii) The learned-helplessness model: exposed to uncontrollable events, animals exhibit learning performance deficit and behavioural changes, including decreased locomotor activity and loss of appetite. (iv) Waiting behaviour: improvement in the ability to wait for and/or postpone an active response; this could be related to the reported beneficial effects of antidepressants on impulsive behaviour.

A new community psychiatric service in Nottingham based on general practice clinics was compared with a conventional hospital-orientated model. Despite providing treatment for an inner-city population of significantly greater social disadvantage, the community service was associated with similar levels of symptom morbidity as assessed by the CPRS and the SFS. It also involved greater use of day-hospital facilities, more extensive multidisciplinary care, and a commitment to longer-term follow-up of chronically ill patients. Such a model is offered as a basis for future developments of urban community psychiatric services.

In-patients suffering from major depressive disorder (endogenous subtype) were randomly allocated to treatment by either traditional ECT with constant-voltage modified sine-wave stimuli (n = 17) or modern, constant-current brief-pulse ECT (n = 14). All treatments were bilateral and monitored by simultaneous recording by EEG. The severity of depressive illness was assessed the day before treatment, after three treatments, and seven days after the last treatment. The improvement and final depression rating scores, the likelihood of recovery, and the average number of treatments received were virtually identical in the two groups. We concluded that the policy of bilateral suprathreshold modern ECT monitored by EEG is as efficacious as traditional ECT.

A model of depression based on measurements made after restraining rats for two hours has been developed. The model is associated with elevation in corticosterone, reflects the higher incidence of depression in women, and shows increased post-synaptic 5-HT function with adaptation. The effects of tianeptine and other antidepressants on the model were studied. Chronic pre-treatment with desipramine, sertraline (amine uptake inhibitors), and chlordiazepoxide normalised open field activity after restraint. Single high doses, post-restraint, of 8-OH-DPAT, gepirone (5-HT agonists), and tianeptine normalised open field activity, whereas desipramine, chlordiazepoxide, and diazepam did not. It is of considerable interest that tianeptine decreased the availability of 5-HT to receptors.

The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and caffeine (400 mg) on subjective and objective measures of cognitive and psychomotor function were compared with placebo in 20 healthy volunteers. While both diazepam and benzhexol were associated with highly significant impairments in subjective alertness, critical flicker fusion threshold and choice reaction time (CRT), haloperidol could not be distinguished from placebo in most tests but was actually associated with an apparent improvement in CRT (in males) and simple visual reaction time. The perceptual maze test detected impairment by benzhexol on processing speed but was not sensitive to any other drug effects. Multiple-dose studies are required to establish if there is a true activating effect of haloperidol using a test of sustained attention. No effect of Eysenck personality subtype or life events on baseline or drug response data was detected.

This paper reviews the epidemiology and pathogenesis of clozapine-associated agranulocytosis. According to present clinical experience, granulocytopenia can be expected in approximately 3% of patients during clozapine treatment. The risk of serious sequelae of granulocytopenia can be minimised by regular white blood cell count monitoring. Although research suggests that some patient groups may be at higher risk of developing this serious adverse reaction, we cannot yet predict the susceptible patients, so all patients exposed to clozapine should receive regular blood monitoring throughout treatment. Because of the risk of agranulocytosis, clozapine should only be used in schizophrenic patients who are resistant to, or intolerant of, conventional antipsychotic medications. Unless compliance with blood monitoring is assured, clozapine treatment should not be recommended.

The features of panic and anxiety in the natural environment were studied by prospective self-monitoring in 39 patients with chronic agoraphobia and panic disorder. Panics overlapped greatly with anxiety episodes but were more intense. Panics occurred more often in public places than did anxiety episodes, but had otherwise similar symptom profile, time of occurrence, and antecedents. Most panics surged out of a pre-existing plateau of tonic anxiety which lasted most of the day. Spontaneous panics were less frequent than situational panics and occurred more often at home but were otherwise similar. These findings do not support the sharp distinction between panic and anxiety in DSM–III–R, not its emphasis on spontaneous panic in classifying anxiety disorders. Thoughts of dying and ‘going crazy’/losing control accompanied only a minority of panic/anxiety episodes and seemed to be a product of intense panic rather than a cause.

The Edinburgh Postnatal Depression Scale (EPDS) was used to rate 217 patients at five days and six weeks post-partum. There was a highly significant positive correlation between the two scores, together with similar symptom profiles. Of the 25 women who suffered postnatal depression (6–week EPDS score ≥13), 17 had similar symptoms in the first week postpartum (5–day EPDS score ≥10). Low birth weight of the baby, delivery by Caesarean section, a delivery much more difficult than expected, and bottle feeding were all significantly associated with a high EPDS score in the first week post-partum. Bottle feeding and delivery by Caesarean section were the only factors associated with depression at the sixth week. A recollection of low mood after a previous birth was also associated with post-natal depression after the current birth. This, together with an EPDS score of 13 or more at five days post-partum, increased the risk of post-natal depression at six weeks 85–fold.

The HRSD, HRSA, SCL–90 scales were psychometrically investigated in a cross-national sample of patients with varieties of non-psychotic symptoms of anxiety and depression. Across the cultural backgrounds the scores obtained from the original versions of these scales are not sufficient statistics. However, latent structure analysis has identified homogeneous subscales for depression (the HRSD) and for discomfort (an SCL subscale). High concurrent validity was found between the subscales of depression, anxiety and discomfort. In international research, inhomogeneity among scale items can be confounded with group differences which are usually ascribed to drug differences.

The treatment of patients with schizophrenia who fail to respond to antipsychotic medications remains a challenge. Despite numerous attempts to establish effective somatic treatment approaches for this population, clozapine appears to be the only well established alternative. Depending upon trial duration and response criteria, between 30% and 60% of previously unresponsive patients appear to derive clinically significant benefit from clozapine. Clozapine also has important advantages in terms of its reduced propensity to produce extrapyramidal side-effects. Agranulocytosis remains an important risk, so strategies to improve the benefit-to-risk ratio should be explored. Issues such as trial duration, dosage, blood levels and predictors of response require additional study.

The time course of clinical improvement was studied in 41 schizophrenic and schizoaffective acute in-patients treated for 28 days with 10, 20 or 30 mg/day of oral fluphenazine hydrochloride in a double-blind, randomised study. Significant improvement was seen in the four BPRS factors: thinking disturbance, hostile-suspiciousness, withdrawal–retardation and anxious depression. The first two of these factors were improved by day 5. Significant improvement was seen up to day 22 for three of the four factors, but without significant improvement during the last week (although scores continued to drop). The half of the sample showing greater overall improvement did not improve faster than the sample as a whole. These more improved subjects did not differ significantly from the less improved subjects in the thinking disturbance factor until day 15, suggesting that at least a two-week neuroleptic trial would be necessary to begin to differentiate more and less responsive patients. The longer-term course of improvement cannot be determined from these data. The withdrawal–retardation and anxious depression factors showed their greatest improvement later than the ‘positive’ symptom factors, suggesting that the former may improve as a result of change in the latter.

Endogenous bromine has been found to be raised during lithium treatment, and it has been suggested that it may augment the therapeutic effect of lithium. Our findings in a study of 12 patients and 12 controls support this contention. Electroencephalographic effects of bromine, vanadium and aluminium were studied – higher bromine and vanadium levels were associated with irregular cortical activity. Electroencephalographic abnormalities were associated with more side-effects of lithium.

Paper and pencil screening tests for depression have never become widely used in the medically ill, despite consensus that a sizeable pool of depression exists in this population. The performance of several self-rating scales in these patients is reviewed, demonstrating that satisfactory screening of depression as defined by standard case criteria can be achieved. It is proposed that it is primarily the absence of clear guidelines for treatment to be used in conjunction with these scales which will make clinicians sceptical of their value. Treatment validation of case criteria is required to demonstrate that screening for depression in medical patients is worthwhile.

The risk for schizophrenia among first-degree relatives of schizophrenic probands obtained from an epidemiological sample using family history methods was examined to determine whether month of birth of the proband was associated with familial risk. The results of this study of the first-degree relatives of 106 female schizophrenics and 275 male schizophrenics suggested that the relatives of probands born in the months February to May had the highest risk, although the association between month of birth and familial risk among the male probands was present only for those relatives who had onset of schizophrenia before the age of 30.

A new scale for the evaluation of feelings of guilt is described. Two types of guilt feeling were of potential interest: ‘delusional’ guilt or shame (experienced in relation to one's actions), and ‘affective’ guilt (a more general feeling of unworthiness). Reliability and validity analyses for the first (15–item) version of the scale were performed in three separate and contrasting clinical samples. The second and final (seven-item) version was tested in another sample of major depressives and in normal controls. The HRSD was used as a measure of severity throughout. The BDI and Widlöcher psychomotor retardation scale were also used as external criteria for the seven-item scale. Exploratory factor analysis of this sample yielded two factors – ‘cognitive/attitudinal’ and ‘mood/feeling’ – of which only the first correlated with scores for psychomotor retardation. It is suggested that these two factors represent two forms of guilt, but that only the former is related to a putative dopaminergic disorder. Guilt scores and measures of severity were not correlated. It is suggested that feelings of guilt should be considered as a behavioural marker for a subtype of depression.

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

In the longitudinal cohort study of young adults from the Canton of Zurich in Switzerland, two groups of eating problems were defined: binge eating and weight concerns. Subjects with these conditions were interviewed at the ages of 27–28 and 29–30 years. The binge eaters, mostly women, differed both from subjects with weight concerns and from controls. They had more severe eating problems and more anxiety and depression. Follow-up as well as retrospective data suggest that eating problems are persistent for the binge eaters, and, to a lesser extent, also for subjects with weight concerns. Even so, professional treatment is rarely sought by subjects with eating problems. These findings encourage long-term studies on eating problems in community samples.