Bipolar disorder is a serious brain disease affecting more than a million individuals living in the USA. Epidemiological studies indicate a role for both genetic and environmental factors in the pathogenesis of this disorder.

To identify RNA transcripts that are up- or down-regulated in the frontal cortex regions of individuals with bipolar disorder.

Serial analysis of gene expression (SAGE) and reverse transcriptase-polymerase chain reaction were used to identify RNA transcripts which are differentially expressed in the frontal cortex of brains obtained postmortem from individuals with bipolar disorder compared with other psychiatric and control conditions.

Levels of RNA transcripts encoding the serotonin transporter protein and components of the NF-κB transcription factor complex are significantly increased in individuals with bipolar disorder compared with unaffected controls. Increased levels of expression of these RNA transcripts were also detected in the brains of some individuals with schizophrenia and unipolar depression.

The SAGE technique offers promise for the characterisation of complex human brain diseases.

A prognosis serves important functions for the management of common mental disorders in primary care.

To establish the accuracy of the general practitioner's (GP) prognosis.

The agreement between GP prognosis and observed course was determined for 138 cases of ICD–10 depression and 65 of generalised anxiety disorder, identified among consecutive attenders of 18 GPs.

Modest agreement between GP prognosis and course was found, both for depression (κ=0.21) and generalised anxiety (κ=0.111). Better agreement (κ=0.45 for depression, and κ=0.33 for generalised anxiety) was observed between the course and predictions from a statistical model based on information potentially available to the GP at the time the prognosis was made. This model assesses attainable performance for GPs.

General practitioners do a fair job in predicting the 1-year course of depression and generalised anxiety. Even so, their performance falls significantly short of attainable performance.

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.

Stigmatisation is of increasing importance in relation to racism, ageism and sexism but also as an impediment to treating patients.

To develop a theoretical foundation to help comprehend the core meaning of stigmatisation and to guide practical anti-stigmatisation measures.

Personal reflection; re-interpretation of stigmatisation and reformulation of the relevant concepts.

Emergence of a unitary theory of stigmatisation.

Based on the structure of stigmatisation one could explore six levels of intervention in anti-stigmatisation campaigns: the cognitive level – educational intervention; the affective level – psychological intervention; the discrimination level – legislative intervention; the denial level – linguistic intervention; the economic origin – political intervention; the evolutionary origin – intellectual and cultural intervention. As destigmatisation has to challenge fundamental human tendencies, anti-stigmatisation campaigns have to be continuous, non-stop, open-ended projects aiming at keeping alive thought processes that moderate and humanise the pursuit of self-interest and the urge to survive in a competitive world.

Many studies have shown an association between obstetric complications and schizophrenia.

To investigate the possible relationship between prenatal underdevelopment, neurodevelopmental abnormality and subsequent schizophrenia.

The literature was reviewed. In particular, by pooling data from recently published reports, we examined whether low birthweight (<2500 g) is a risk factor for schizophrenia.

Low birthweight was significantly more common for subjects with schizophrenia than for control subjects: P < 0.00001, odds ratio 2.6 (95% CI 2.0 to 3.3). Individuals born prematurely are at greater risk of perinatal brain damage and subsequent neurodevelopmental abnormalities, which may constitute vulnerability to the development of schizophrenia. Patients with schizophrenia who had low birthweights also tended to have poor premorbid psychosocial adjustment.

Low birthweight is a modest, but definite, risk factor for schizophrenia. Brain damage associated with prenatal underdevelopment has a role in the pathogenesis of poor premorbid functioning and subsequent neurodevelopmental impairment in some cases of schizophrenia.

Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia.

To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables.

Historic prospective study. Standardised assessments of course and outcome.

About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery.

A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

Despite the growing recognition of the global burden of psychiatric disease, there are questions about the strength of the evidence base from non-Western societies.

To compare the contribution of Euro-American countries and the rest of the world (RoW) to psychiatric literature.

Survey of the country of origin of papers submitted to and published in six leading psychiatric journals over a 3-year period (1996–1998).

Only 6% of the literature is published from regions of the world that account for over 90% of global population. The three journals published in Europe had a significantly higher proportion of international articles when compared to the three American journals. Less than 1% of all published articles described mental health interventions in the RoW. Acceptance rates were significantly lower for papers submitted from the RoW.

There is a gross under-representation of research from the RoW. This has implications for the development of a truly international psychiatry.

Cannabis is commonly regarded as an innocuous drug and the prevalence of lifetime and regular use has increased in most developed countries. However, accumulative evidence highlights the risks of dependence and other adverse effects, particularly among people with pre-existing psychiatric disorders.

To re-evaluate the adverse effects of cannabis in the general population and among vulnerable individuals, including those with serious psychiatric disorders.

A wide-ranging review of the topics related to these issues.

An appreciable proportion of cannabis users report short-lived adverse effects, including psychotic states following heavy consumption, and regular users are at risk of dependence. People with major mental illnesses such as schizophrenia are especially vulnerable in that cannabis generally provokes relapse and aggravates existing symptoms. Health workers need to recognise, and respond to, the adverse effects of cannabis on mental health.

Neuroimaging data showing structural and functional brain abnormalities in mood disorders suggest that brain alterations at the neurohistological level may underlie the macropathology seen by imaging in vivo.

To summarise recent post-mortem studies on affective disorders, with a focus on bipolar disorder.

Literature review and discussion of results from volumetric, cyto-architectural and immunohistochemical analyses.

Basal ganglia are smaller in patients with depression irrespective of diagnostic polarity. In addition, higher neuron numbers have been reported in the locus caeruleus of patients with bipolar disorder compared with those with unipolar depression. Patients with bipolar as well as unipolar illness show subtle structural deficits in the dorsal raphe. Histological data are consistent with a regional reduction in the synthesis of noradrenalin and serotonin, which appears to be compensated by antidepressants.

Preliminary results suggest that, aside from functional dysregulation, subtle structural abnormalities in the brain may contribute to the pathogenesis of mood disorders.

Little is known about predictors of hospitalisation in patients with first-episode psychosis.

To identify the pattern and predictors of hospitalisation of patients with a first psychotic episode making their first contact with specialist services.

Three-year follow-up of a cohort of 166 patients with a first episode of psychosis making contact with psychiatric services in Nottingham between June 1992 and May 1994.

Eighty-eight (53.0%) patients were admitted within 1 week of presentation; 32 (19.3%) were never admitted during the 3 years of follow-up. Manic symptoms at presentation were associated with an increased risk of rapid admission and an increased overall risk of admission; negative symptoms and a longer duration of untreated illness had an increased risk of late admission.

Community-oriented psychiatric services might only delay, rather than prevent, admission of patients with predominantly negative symptoms and a longer duration of untreated illness. First-episode studies based upon first admissions are likely to be subject to selection biases, which may limit their representativeness.

Cannabis policy continues to be controversial in North America, Europe and Australia.

To inform this debate, we examine alternative legal regimes for controlling cannabis availability and use.

We review evidence on the effects of cannabis depenalisation in the USA, Australia and The Netherlands. We update and extend our previous (MacCoun & Reuter, 1997) empirical comparison of cannabis prevalence statistics in the USA, The Netherlands and other European nations.

The available evidence indicates that depenalisation of the possession of small quantities of cannabis does not increase cannabis prevalence. The Dutch experience suggests that commercial promotion and sales may significantly increase cannabis prevalence.

Alternatives to an aggressively enforced cannabis prohibition are feasible and merit serious consideration. A model of depenalised possession and personal cultivation has many of the advantages of outright legalisation with few of its risks.

Stroke, hypertension and diabetes are common in older Caribbean-born populations in the UK who may be at risk of depression secondary to vascular disease.

We examined the association between stroke, vascular risk factors and depression in a community-based Caribbean-born population aged 55–75 years.

Vascular risk factors were identified by interview, examination and blood tests. Depression was categorised using the Geriatric Depression Scale. Disablement was assessed as a potential mediating factor.

Physical illness and disablement were strongly associated with depression, independent of disablement. Previous stroke was associated with depression, independent of disablement. No vascular risk factors were associated with depression.

The risk of depression associated with stroke was not explained by disablement. However, the hypothesis that vascular risk factors are important in the genesis of depression was not supported.

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.

During recent years the strategy for aetiological research in schizophrenia has been to concentrate on two closely connected directions: the search for the genetic element and the search for environmental factors. Damage to the immature brain during pregnancy and delivery has given us the most interesting results from recent environmental research.

To examine the validity of the influenza-schizophrenia hypothesis.

A review of register-based epidemiological studies in Denmark conducted over a 10-year period.

The studies reviewed provided strong inferential evidence in favour of the hypothesis, but some methodological problems are unresolved and not all replication studies have been positive.

The brain-damage hypothesis points to possibilities for identifying high-risk individuals at an early stage of life and perhaps establishing specific preventive programmes. There is, however, a great need for closer international collaboration in future research.

Currently, without systematic evidence, psychotherapy for anorexia nervosa in adults draws on psychodynamic, cognitive and systemic theories.

To assess effectiveness of specific psychotherapies in out-patient management of adult patients with anorexia nervosa.

Eighty-four patients were randomised to four treatments: three specific psychotherapies – (a) a year of focal psychoanalytic psychotherapy; (b) 7 months of cognitive-analytic therapy (CAT); (c) family therapy for 1 year – and (d) low contact, ‘routine’ treatment for 1 year (control).

At 1 year, there was symptomatic improvement in the whole group of patients. This improvement was modest, several patients being significantly undernourished at follow-up. Psychoanalytic psychotherapy and family therapy were significantly superior to the control treatment; CAT tended to show benefits.

Psychoanalytic and family therapy are of specific value in the out-patient treatment of adult patients with anorexia.

Progress in identifying genetic factors protective against alcohol dependence (AIcD) requires a paradigm shift in psychiatric epidemiology.

To integrate analysis of research into the genetics of alcoholism.

Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed.

In men, effects of alcohol dehydrogenase ADH2∗1/∗2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AIcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AIcD symptoms. No protective effect of the ADH2∗1/∗2 genotype was observed in women.

The early onset and strong familial aggregation of AIcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

It has been hypothesised that the association between greater income inequality and increased mortality is mediated by poor psychosocial health.

To test the hypothesis that individuals in regions of Britain with the highest income inequality have a higher prevalence of the common mental disorders, after adjusting for individual income.

Cross-sectional survey of 8191 adults aged 16–75 in private households in England, Wales and Scotland. The prevalence of common mental disorders was assessed using the General Health Questionnaire.

The association between income inequality and prevalence of the common mental disorders varied with individual income level. Among persons with the highest incomes, common mental disorders were more frequent in regions with greater income inequality (as indicated by high Gini coefficient) (adjusted OR 1.31, 95% CI 1.05–1.65; P=0.02). The opposite was true for those with the lowest incomes.

Income inequality was associated with worse mental health among the most affluent individuals.

Tricyclic antidepressants have similar efficacy and slightly lower tolerability than selective serotonin reuptake inhibitors (SSRIs). However, there are no systematic reviews assessing amitriptyline, the reference tricyclic drug, v. other tricyclics and SSRIs directly.

To review the tolerability and efficacy of amitriptyline in the management of depression.

A systematic review of randomised controlled trials (RCTs) comparing amitriptyline with other tricyclics/heterocyclics or with an SSRI.

We reviewed 186 RCTs. The overall estimate of the efficacy of amitriptyline revealed a standardised mean difference of 0.147 (95% CI 0.05–0.243), significantly favouring amitriptyline. The overall OR for dropping out was 0.99 (95% CI 0.91–1.08) and that for side-effects was 0.62 (95% CI 0.54–0.70), favouring the control drugs. With drop-outs included as treatment failures, the estimate of the effectiveness of amitriptyline v. tricyclics/heterocyclics and SSRIs showed a 2.5% difference in the proportion of responders in favour of amitriptyline (number needed to treat 40, CI 21–694; OR 1.12 (95%CI 1.01–1.24)).

Amitriptyline is less well tolerated than tricyclics/heterocyclics and SSRIs, but slightly more patients treated on it recover than on alternative antidepressants.