Genetics is increasingly being used to explain human behaviours, with growing enthusiasm for what could be termed ‘genetic determinism’, which an ultra-Darwinist approach seeks to apply to all aspects of the human condition.

To consider the validity of the claims concerning the genetics of human behaviour and psychological distress.

A critical review of the current assumptions about the relative contributions of genetics and the environment.

Organisms are in constant interaction with their environment: that is, organisms select environments just as environments select organisms. Like organisms, environments evolve and are homeodynamic rather than homeostatic; both ‘genome’ and ‘envirome’ are abstractions from this continuous dialectic.

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.

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.

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.

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.

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.

Multivariate genetic research indicates that genetic effects on diverse cognitive abilities are general rather than specific or modular. General cognitive ability (g), a key factor in learning and memory, is among the most heritable behavioural traits.

To give a brief overview of quantitative genetic research on g and to describe initial results from a programme of research that aims to identify genes responsible for the substantial heritability of general cognitive ability.

The research uses a new technique called DNA pooling, which combines DNA from individuals within a group and makes it feasible to screen thousands of DNA markers for a systematic scan of the genome for associations between DNA markers and g. Two independent samples of children with very high g scores and two control samples of children with average g scores were compared in a systematic scan of 147 markers on chromosome 4 and 66 markers on chromosome 22.

Three replicated associations on chromosome 4 were identified using DNA pooling and confirmed using individual genotyping.

These first results of the application of DNA pooling in systematic analysis of allelic association are encouraging.

From 1978 to 1979, a group of people in Taiwan were exposed to high levels of heat-degraded polychlorinated biphenyls (PCBs) owing to accidental ingestion of contaminated rice oil. Children born to mothers following the exposure (‘Yucheng’ children) were known to have hyperpigmented skin and other dysmorphology after birth.

To determine the effect of prenatal exposure to PCBs on cognitive development in Yucheng children.

One hundred and eighteen Yucheng children prenatally exposed to PCBs and degradation products, and community-matched control children who were exposed to background levels only, were followed from 1985 to 1998. The Bayley Scale for Infant Development, Chinese version of the Stanford – Binet IQTest, Raven's Coloured Progressive Matrices and Raven's Standardised Progressive Matrices were used to assess the cognitive development of these children.

The Yucheng children scored lower than control children on each of these methods of measurement between the ages of 2 and 12 years.

Prenatal exposure to PCBs and their derivatives has long-term adverse effects on cognitive development in humans.

Alzheimer's disease (AD) is a common, complex, age-related disorder in which both genetic and environmental factors are important.

To integrate recent studies on genetic and environmental factors in AD into a multi-factorial disease model.

Disease models to explain gene-environment interaction in cardiovascular disease are related to observations on AD.

Informative, community-based studies on the genetic epidemiology of AD are rare. Putative risk factors from the Scottish studies include increased paternal age in AD men and coal mining as paternal occupation in both AD and vascular dementia. Migration effects suggest that environmental factors in high-incidence AD areas are important during adult life.

The studies summarised do not provide sufficient data to support a single comprehensive disease model of gene-environment interaction in AD. Future studies will require very large (≥600) sample sizes, molecular genetic analysis, and environmental data that span neurodevelopment and the period between disease onset and appearance of clinical symptoms.

Increased rates of schizophrenia continue to be reported among the African–Caribbean population in England.

To evaluate the competing biological, psychological and social explanations that have been proposed.

Literature review.

The African–Caribbean population in England is at increased risk of both schizophrenia and mania; the higher rates remain when operational diagnostic criteria are used. The excess of the two psychotic disorders are probably linked: African–Caribbean patients with schizophrenia show more affective symptoms, and a more relapsing course with greater social disruption but fewer chronic negative symptoms, than White patients. No simple hypothesis explains these findings.

More complex hypotheses are needed. One such links cultural variation in symptom reporting, the use of phenomenological constructs by psychiatrists and social disadvantage.

Twin studies suggest that shared early family environment is of only minor importance in the aetiology of depression, most of the variance being attributable either to genetic or to individual ‘non-shared’ environmental factors.

To examine the respective roles of personality and social experiences on the risk for common mental disorders, with special reference to depression.

Analysis of preliminary findings from two large-scale British population surveys: (a) a multi-centre study of general practice patients, and (b) a study of working-class women in Manchester.

(a) Persons recently separated from their partners have raised mean scores for psychological distress, but the relative excess is due entirely to persons with high ratings for introversion; (b) while severe life events were associated with physiological responses characteristic of depression, the probability of experiencing such life events varied between 0.2 monthly for low scorers and 1.5 monthly for high scorers on a vulnerability measure.

Social factors do appear to influence the prevalence of depression, but this effect is not independent of genetically determined vulnerability.

There is some evidence that genetic effects on the likelihood of experiencing stressful life events (SLEs) are mediated by heritable traits such as cognitive ability (CA) and neuroticism (N).

To examine whether the association between CA, N and mental ill-health is driven in part by a predisposition to experience depressogenic SLEs.

Childhood measures of N and CA were available in a birth cohort of 5362 individuals. At ages 36 and 43 years, mental state and occurrence of SLEs in the previous year were assessed. Using a path-analytic approach, models with and without a hypothesised influence of N and CA on the occurrence of SLEs were compared.

The fit of the model with childhood N having a direct influence on SLEs was good with χ2=5.72, d.f.=4, P=0.22 at age 36 years and χ2=3.50, d.f.=5, P=0.62 at age 43. The fit of the model was significantly worse without this path at both ages (36 years: χ2=42,5, d.f.=1, P<0.001; 43 years χ2=15.3 d.f.=1, P<0.001). No consistent differences were seen in comparisons of models with CA.

The results are congruent with the suggestion that genetic effects on SLEs are mediated by personal characteristics. Part of the well-established association between N and minor psychiatric disorder may be mediated by an indirect effect of N on the likelihood of experiencing SLEs.

Previous investigations into the impact of birth complications and social environment have generally followed their subjects only at young ages.

To assess the long-range impact of socio-economic status (SES) and birth risks on the development of emotional and nervous conditions through adulthood.

The Johns Hopkins Pathways Study interviewed 1824 subjects born between 1960 and 1965. The median household income of the children at age 7–8 years was used to divide the cohort into high and low income categories. Differences in lifetime prevalence of emotional and nervous conditions through adulthood between the two income groups were identified.

Children in the lower income group were 1.86 times more likely to report an emotional or nervous condition in adult life. Boys in the lower income group at age 7–8 years were 3.2 times more likely to do so. The risks of difficult birth for adult mental disturbance were accentuated in the low-income group.

Children who experience birth complications are at increased risk of developing adult mental disturbances; this increase is mitigated by higher SES.

Generations of epidemiologists have documented an association between low socio-economic status (SES) and depression (variously defined), but debate continues as to which is the causative factor.

To test the extent to which social causation (low SES causing depression) and social selection (depression causing low SES) processes are in evidence in an inter-generational longitudinal study.

Participants (n=756) were interviewed up to four times over 17 years using the Schedule for Affective Disorders and Schizophrenia (SADS).

Low parental education was associated with increased risk for offspring depression, even after controlling for parental depression, offspring gender and offspring age. Neither parental nor offspring depression predicted later levels of offspring occupation, education or income.

There is evidence for an effect of parental SES on offspring depression (social causation) but not for an effect of either parental or offspring depression on offspring SES (social selection).

Evidence from twin and adoption studies has highlighted the importance of gene-environment interaction in the aetiology of mental disorders, and advances in molecular genetics have raised hopes of more rapid progress in this field of investigation.

To review epidemiological knowledge concerning genetic and environmental risk factors for a cross-section of psychiatric conditions, and evidence of interaction between the two types.

Searches of the literature in genetic and psychiatric epidemiology, including contributions to this supplement.

Overall, firm knowledge on both genetic and environmental causal factors is still fragmentary, although progress has varied among diagnostic categories. Environmental aspects have been dealt with only perfunctorily in most genetic epidemiological research.

Better definition and classification of environmental hazards, and closer inter-disciplinary cooperation, will be necessary in future. Specific gene-environment interaction effects seem likely to prove most important in neuropsychiatric syndromes, and a less specific genetic influence on susceptibility to environmental stress among the common mental disorders.