The human genome dwells within environment, determines environment and its expression is shaped by environment.

To introduce ‘psychiatric enviromics’ as a complement to human genomics and proteomics as applied to mental health.

Selective literature review and synthesis.

Psychiatric enviromics can be planned to sustain the search for specific environments or environmental processes and conditions that promote mental health and reduce the occurrence of psychiatric disturbances. Subsets of the psychiatric envirome will be discovered to have functional importance precisely because specific environmental conditions or processes will reduce, amplify or otherwise modulate the expression of specific genes or multiple gene interactions at identifiable periods of life-span development. Other salubrious environmental conditions and processes will have funtional importance but lack specificity of action with respect to gene expression. An international collaboration in the form of a review of evidence is proposed as a starting point for ‘psychatric enviromics’.

In order to understand studies of psychiatric epidemiology focusing on the ‘genome’ and ‘envirome’, basic knowledge of the logic and methods is necessary.

To provide a review of typical methods used in genetic epidemiology.

Reviews of the research designs usually employed in quantitative and molecular genetic studies. Genotype-environment correlation and interaction are also discussed.

Quantitative genetic studies indicate that genetic influences are important for both psychiatric disorders and behavioural traits. Specific gene loci can be tested for associations with both psychiatric risk and behavioural traits by means of molecular genetic techniques. There has been little examination of genotype-environment correlation and interaction, although the few reports that have appeared suggest that these complex relationships are important.

Advances in quantitative and molecular genetics now permit more careful examination of genotype-environment interaction and correlation. Studies combining molecular genetic strategies with measurement of the environment are still at an early stage, however, and their results must be awaited.

Increasing prevalence of recreational cannabis use among the young population has stimulated debate on the possible effects of acute and long-term use.

To highlight recent knowledge of mechanisms of action, effects on psychomotor and cognitive performance, and health risks associated with cannabis consumption.

A brief review of recent literature on the prevalence of recreational cannabis use, the potency of modern cannabis preparations and the pharmacological actions of cannabis.

Cannabinoids derived from herbal cannabis interact with endogenous cannabinoid systems in the body. Actions on specific brain receptors cause dose-related impairments of psychomotor performance with implications for car and train driving, aeroplane piloting and academic performance. Other constituents of cannabis smoke carry respiratory and cardiovascular health risks similar to those of tobacco smoke.

Cannabis is not, as widely perceived, a harmless drug but poses risks to the individual and to society.

A robust body of evidence from family, twin and adoption studies demonstrates the importance of genes in the pathogenesis of bipolar disorder. Recent advances in molecular genetics have made it possible to identify these susceptibility genes.

To present an overview for clinical psychiatrists.

Review of current molecular genetics approaches and emerging findings.

Occasional families may exist in which a single gene plays a major role in determining susceptibility, but the majority of bipolar disorder involves more complex genetic mechanisms such as the interaction of multiple genes and environmental factors. Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest include chromosomes 4p16, 12q23–q24, 16p13, 21q22, and Xq24–q26. Candidate gene association studies are in progress but no robust positive findings have yet emerged.

It is almost certain that over the next few years the identification of bipolar susceptiblity genes will have a major impact on our understanding of disease pathophysiology. This is likely to lead to major improvements and treatment in patient care, but will also raise important ethical issues.

Clinicians are increasingly asked by relatives of patients with Alzheimer's disease to advise on their genetic risk of developing Alzheimer's disease in later life. Many clinicians find this a difficult question to answer.

To provide information for old age psychiatrists wishing to advise relatives of their risk of developing Alzheimer's disease.

A selective review of the key literature on the genetic epidemiology of Alzheimer's disease.

Currently a DNA diagnosis is attainable in some 70% of families with autosomal dominant Alzheimer's disease. In first-degree relatives of most cases, risk is increased some three- or four-fold relative to controls, but only one-third of this is realised in the average life span. Apolipoprotein E genotyping cannot be used as a predictive test and confers only minimal diagnostic benefit.

Pedigrees with familial Alzheimer's disease should be referred to a Regional Centre for Medical Genetics. Accurate risk prediction is not possible in the vast majority of pedigrees with Alzheimer's disease, although it is possible for the psychiatrist to give a rough estimate of the risk, which can reasonably the couched in reassuring terms.

Community mental health teams are now generally recommended for the management of severe mental illness but a comparative evaluation of their effectiveness is lacking.

To assess the benefits of community mental health team management in severe mental illness.

A systematic review was conducted of community mental health team management compared with other standard approaches.

Community mental health team management is associated with fewer deaths by suicide and in suspicious circumstances (odds ratio=0.32, 95% CI 0.09–1.12), less dissatisfaction with care (odds ratio=0.34, 95% CI 0.2–0.59) and fewer drop-outs (odds ratio=0.61, 95% CI 0.45–0.83). Duration of in-patient psychiatric treatment is shorter with community team management and costs of care are less, but there are no gains in clinical symptomatology or social functioning.

Community mental health team management is superior to standard care in promoting greater acceptance of treatment, and may also reduce hospital admission and avoid deaths by suicide. This model of care is effective and deserves encouragement.

Genetic factors are known to be important in the aetiology of bipolar disorder.

To review linkage studies in extended families multiply affected with bipolar disorder.

Selective review of linkage studies of bipolar disorder emphasising the gains and drawbacks of studying large multiply-affected families and comparing the statistical methods used for data analysis.

Linkage of bipolar disorder to several chromosome regions including 4p, 4q, 10p, 12q, 16p, 18q, 21q and Xq has first been reported in extended families. In other families chromosomal rearrangements associated with affective illnesses provide signposts to the location of disease-related genes. Statistical analyses using variance component methods can be applied to extended families, require no prior knowledge of the disease inheritance, and can test multilocus models.

Studying single large pedigrees combined with variance component analysis is an efficient and effective strategy likely to lead to further insights into the genetic basis of bipolar disorders.

Health inequalities exist for many disorders, but the contribution of deprivation to the prevalence and outcome of depressive symptoms in primary care populations has been infrequently studied.

To examine the influence of Jarman under-privileged area (UPA) scores on the prevalence and outcome of depressive symptoms in general practice patients.

18 414 patients attending 55 representative practices completed the Hospital Anxiety and Depression Scale and a questionnaire for employment status. Outcome of those screening positive was assessed at 6 weeks and 6 months.

The UPA score accounted for 48.3% of the variance between practices in prevalence of depressive symptoms. Attending a high UPA score practice predicted persistence of depressive symptoms to 6 months.

The socio-economic deprivation of a practice locality is a powerful predictor of the prevalence and persistence of depressive symptoms.

Data from family, twin and adoption studies show overwhelming evidence of a substantial genetic component in schizophrenia and although molecular genetic studies have been more difficult to replicate, recent improvements in technology have resulted in the implication of genes at several chromosomal loci. Nevertheless, it remains clear that environmental factors both add to and interact with genetic factors to produce the disorder.

To incorporate genetic and environmental risk factors into a neurodevelopmental model in order to conceptualise the liability to schizophrenia.

A representative selection of the literature related to this issue is reviewed, together with a reformulation of Meehl's term ‘schizotaxia’ to describe the liability to the disorder.

The literature supports a multi-factorial view of the liability to schizophrenia, which includes both genetic and environmental components.

Schizotaxia provides a useful way to conceptualise both the liability for schizophrenia, and also the development of treatment strategies aimed at the eventual prevention of the illness.

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.

While depression is known to involve a disturbance of mood, movement and cognition, its associated cognitive deficits are frequently viewed as simple epiphenomena of the disorder.

To review the status of cognitive deficits in depression and their putative neurobiological underpinnings.

Selective computerised review of the literature examining cognitive deficits in depression and their brain correlates.

Recent studies report both mnemonic deficits and the presence of executive impairment – possibly selective for set-shifting tasks – in depression. Many studies suggest that these occur independent of age, depression severity and subtype, task ‘difficulty’, motivation and response bias: some persist upon clinical ‘recovery’.

M nemonic and executive deficits do not appear to be epiphenomena of depressive disorder. A focus on the interactions between motivation, affect and cognitive function may allow greater understanding of the interplay between key aspects of the dorsal and ventral aspects of the prefrontal cortex in depression.

Over the past 10 years the technique of tryptophan depletion has been used increasingly as a tool for studying brain serotonergic systems.

To review the technique of tryptophan depletion and its current status as a tool for investigating psychiatric disorders.

Systematic review of preclinical and clinical studies.

Tryptophan depletion produces a marked reduction in plasma tryptophan and consequently brain serotonin (5-HT) synthesis and release. In healthy volunteers the effects of tryptophan depletion are influenced by the characteristics of the subjects and include some mood lowering, some memory impairment and an increase in aggression. In patients with depression tryptophan depletion tends to result in no worsening of depression in untreated subjects but a relapse in those who have responded to antidepressants (particularly serotonergic agents). In panic disorder the results are similar.

The findings that tryptophan depletion produces a relapse of symptoms in patients with depression and panic disorder who have responded to treatment with antidepressants suggests that enhanced 5-HT function is important in maintaining response in these conditions.

Review commissioned in 1996 by the Department of Health (DOH).

Assess therapeutic profile of cannabis and cannabinoids.

Medline search, references supplied by DOH and others, and personal communications.

Cannabis and some cannabinoids are effective antiemetics and analgesics and reduce intraocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.