New research in animals is beginning to change radically our understanding of the biology of stress and the effects of antidepressant agents.

To relate recent findings from the basic neurosciences to the pathophysiology of depressive disorder.

Drawing together findings from molecular and physiological studies in rats, social studies in primates and neuropsychological studies in humans, we review the neurotrophic and neuroplastic effects of antidepressants and stress.

Stress and antidepressants have reciprocal actions on neuronal growth and vulnerability (mediated by the expression of neurotrophins) and synaptic plasticity (mediated by excitatory amino acid neurotransmission) in the hippocampus and other brain structures. Stressors have the capacity to progressively disrupt both the activities of individual cells and the operating characteristics of networks of neurons throughout the life cycle, while antidepressant treatments act to reverse such injurious effects.

We propose a central role for the regulation of synaptic connectivity in the pathophysiology of depressive disorder.

Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression.

Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression.

Patients 18–65 years of age with recurrent unipolar major depression (DSM–IV), a Montgomery–åsberg Depression Rating Scale score of ≥ 22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20–60 mg) for 6–9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48–77 weeks.

A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P < 0.001). Prophylactic treatment was well tolerated.

Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.

Studies of light therapy have not been conducted previously in primary care.

To evaluate light therapy in primary care.

Fifty-seven participants with seasonal affective disorder were randomly allocated to 4 weeks of bright white or dim red light. Baseline expectations for treatment were assessed. Outcome was assessed with the Structured Interview Guide for the Hamilton Depression Scale, Seasonal Affective Disorder Version.

Both groups showed decreases in symptom scores of more than 40%. There were no differences in proportions of responders in either group, regardless of the remission criteria applied, with around 60% (74% white light, 57% red light) meeting broad criteria for response and 31% (30% white light, 33% red light) meeting strict criteria. There were no differences in treatment expectations.

Primary care patients with seasonal affective disorder improve after light therapy, but bright white light is not associated with greater improvements.

Many patients with depression take benzodiazepine drugs long term despite the absence of continuing therapeutic value.

To evaluate a treatment programme involving gradual discontinuation with or without simultaneous selective serotonin reuptake inhibitor (SSRI) prescribing and to determine the long-term outcome after benzodiazepine withdrawal.

Patients went through three phases – change to an equivalent dose of diazepam; subsequent randomisation to either 20 mg of paroxetine or placebo; and gradual reduction of diazepam in depression-free patients – with a follow-up after 2 or 3 years.

A total of 230 patients were recruited and 75% in the paroxetine group and 61% in the placebo group were successfully treated after 6 weeks (P=0.067). After 2 or 3 years 13% of patients were still benzodiazepine free: 26% of those who had successfully tapered off benzodiazepine and 6% of the total group.

Transfer to diazepam followed by gradual withdrawal is an effective way of discontinuing chronic benzodiazepine use. The addition of SSRI treatment is of limited value.

Erectile dysfunction is a common, multi-factorial disorder.

To evaluate the efficacy, tolerability and frequency of use of sildenafil citrate in men with mild to moderate erectile dysfunction of no established organic cause.

This double-blind, randomised, placebo-controlled, flexible-dose, two-way crossover study was conducted at four centres in the UK in 44 men with mild to moderate erectile dysfunction of no clinically obvious organic cause. The study included two 28-day treatment periods, during which time sildenafil or placebo (25–75 mg, based on efficacy) was taken as required.

Compared with placebo, sildenafil was associated with increases in frequency of use, erections adequate for sexual intercourse and level of sexual satisfaction (P < 0.0001). More patients receiving sildenafil stated they would use the treatment again compared with those receiving placebo (P < 0.0001). There were no discontinuations due to sildenafil treatment.

Sildenafil is effective and well tolerated in men with mild to moderate erectile dysfunction of no clinically identifiable organic cause.

Exposure to external phobic cues is an effective therapy for panic/agoraphobia but the value of exposure to interoceptive cues is unclear.

Randomised controlled comparison in panic/agoraphobia of the effects of (a) external, (b) interoceptive or (c) combined external and interoceptive self-exposure to (d) control subjects.

Eighty out-patients were randomised to a control group or to one of three forms of self-exposure treatment (external, interoceptive, or combined). Each treatment included seven sessions over 10 weeks and daily self-exposure homework. Assessments were at pre- and post-treatment and up to 1 year post-entry. Assessors remained blind during treatment.

The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year follow-up, and significantly more than did the control subjects. Rates of improvement on main outcome measures averaged 60% at post-treatment and 77% at follow-up.

The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term.

It has been suggested that there is frontal lobe involvement in schizophrenia, and that it may be lateralised and gender-specific.

To clarify the structure of the frontal lobes in schizophrenia in a postmortem series.

The volume of white matter and cortical components of the frontal lobes was measured in brains of controls and patients with schizophrenia using planimetry and the Cavalieri principle. The components measured were: superior frontal gyrus, middle frontal gyrus, a composite of inferior frontal gyrus and orbito-frontal cortex, as well as total frontal lobe cortex and white matter. In addition, the anterior cingulate gyrus was measured.

No diagnosis, gender, diagnosis × side, diagnosis × gender or diagnosis × gender × side interactions were observed in the volume of any of the components, the grey matter as a whole or the white matter. No evidence for volumetric inter-group differences was found for the anterior cingulate gyrus.

Such structural abnormalities as are present in the frontal lobes are more subtle than straightforward alterations in tissue volume; they may include changes in shape and the pattern of gyral folding.

Cerebral lateralisation appears to be decreased in schizophrenia. Results of studies investigating this, however, are equivocal.

To review quantitatively the literature on decreased lateralisation in schizophrenia.

Meta-analyses were conducted on 19 studies on handedness, 10 dichotic listening studies and 39 studies investigating anatomical asymmetry in schizophrenia.

The prevalence of mixed- and left-handedness (‘non-right-handedness’) was significantly higher in patients with schizophrenia as compared to healthy controls, and also as compared to psychiatric controls. The analysis of dichotic listening studies revealed no significant difference in lateralisation in schizophrenia. However, when analysis was restricted to studies using consonant-vowel or fused word tasks, significantly decreased lateralisation in schizophrenia emerged. Asymmetry of the planum temporale and the Sylvian fissure was significantly decreased in schizophrenia, while asymmetry of the temporal horn of the lateral ventricle was not.

Strong evidence is provided for decreased cerebral lateralisation in schizophrenia.

Reduced serotonergic (5-HT) function and elevated testosterone have been reported in aggressive populations.

To investigate relationships between impulsivity, aggression, 5-HT function and testosterone in male offenders with personality disorders.

Sixty male offenders with DSM–III–R personality disorders and 27 healthy staff controls were assessed using the Special Hospital Assessment of Personality and Socialisation (SHAPS), impulsivity and aggression ratings, d-fenfluramine challenge and plasma hormone concentrations.

The SHAPS non-psychopaths and those with schizoid personality disorders had enhanced 5-HT function (prolactin response to d-fenfluramine). Reduced 5-HT function was found in offenders with DSM–III–R borderline personality disorders and those with a history of repeated self-harm or alcohol misuse. The 5-HT function was inversely correlated more strongly with impulsivity than with aggression. Plasma testosterone correlated positively with aggressive acts. The SHAPS primary psychopaths had lower initial cortisol and higher testosterone concentrations than controls.

Future studies are needed to investigate regional brain 5-HT function.

Anaesthesia could provoke persistent alterations in specific cognitive domains in the elderly where ageing-related neuronal changes may exacerbate pharmacotoxic effects.

To evaluate anaesthesia effects on the incidence of cognitive dysfunction after orthopaedic surgery in elderly patients.

A total of 140 patients over the age of 64 years completed a full range of computerised cognitive tests. The study takes into account effects of pre-operative cognitive dysfunction, depressive symptomatology and ability to perform activities of daily living.

Postoperative cognitive decline persisted for up to 3 months in 56% of subjects. Dysfunction was limited to verbal, visuo-spatial and semantic abilities and secondary and implicit memory. Age, low educational level, pre-operative cognitive impairment or depression are risk factors.

Cognitive functions are not equally affected, type of impairment being determined by the risk factors described above and anaesthesia type.

Previous reports on the incidence of schizophrenia in immigrant groups to The Netherlands were based on hospital data.

To compare the incidence of psychotic disorders in the immigrant groups to that in natives.

Two-year first-contact incidence study in The Hague.

The risks of schizophrenia, schizophreniform or schizoaffective disorder (DSM–IV criteria) were increased for subjects born in Morocco (gender and age-adjusted relative risk=4.5; 95% CI 1.4–8.5), Surinam (relative risk=3.2; 1.8–5.7), The Netherlands Antilles (relative risk=2.9; 0.9–9.5) and other non-Western countries (relative risk=2.4; 1.3–4.7). This risk was also increased for Moroccans (relative risk=8.0; 2.6–24.5) and Surinamese (relative risk=5.5; 2.5–11.9) of the second generation. The risks for Turkish immigrants, first or second generation, and for immigrants from Western countries were not significantly increased.

This study indicates that the incidence of schizophrenia is increased in several, but not all, immigrant groups to The Netherlands. It is possible that factors associated with a process of rapid westernisation precipitate schizophrenia in people who are genetically at risk.

The impact on individual survivors of human rights abuses of testifying before South Africa's Truth and Reconciliation Commission (TRC) has not been established.

To examine the degree to which participation in the TRC is related to current psychiatric status and forgiveness among survivors.

Survivors (n=134) who gave public, closed or no testimony to the TRC completed instruments measuring exposure to human rights abuses, exposure to other traumatic events, current psychiatric status and forgiveness attitudes towards the perpetrator(s).

There was no significant association between TRC participation and current psychiatric status or current forgiveness attitudes, and low forgiveness was associated with poorer psychiatric health.

Truth commissions should form part of, rather than be a substitute for, comprehensive therapeutic interventions for survivors of human rights abuses. Lack of forgiveness may be an important predictor of psychiatric risk in this population.