Twin studies demonstrate the importance of genes and environment in the aetiology of childhood psychiatric and neurodevelopmental disorders. Advances in molecular genetics enable the identification of genes involved in complex disorders and enable the study of molecular mechanisms and gene–environment interactions.

To review the role of molecular genetics studies in childhood behavioural and developmental traits.

Molecular approaches to complex disorders are reviewed, with examples from autism, reading disability and attention-deficit hyperactivity disorder (ADHD).

The most robust finding in ADHD is the association of a variable number tandem repeat polymorphism in exon 3 of the DRD4 gene. Other replicated associations with ADHD are outlined in the text. In autism, there is a replicated linkage finding on chromosome 7. Linkage studies in reading disability have confirmed a locus on chromosome 6 and strongly suggest one on chromosome 15.

In the next 5–10 years susceptibility genes for these disorders will be established. Describing their relationship to biological and behavioural function will be a far greater challenge.

Most studies of the recognition of depression in primary care have used a categorical definition of depression. This may overstate the extent of the problem.

Our objective was to investigate the relationship between severity and recognition of depression, and its modification by patient and practitioner characteristics.

An association study in multiple consecutive adult cohorts of 18 414 primary care consultations drawn from a representative sample of 156 general practitioners in Hampshire, UK.

There was a curvilinear relationship between the severity of depression and practitioners' ratings of depression. One case of probable depression was missed in every 28.6 consultations. Anxiety and unemployment altered the chances of recognition, but age, gender and deprivation scores did not.

A dimensional approach to severity of depression shows that general practitioners may be better able to recognise depression than previous categorical studies have suggested. Efforts to improve the care of depression should therefore focus on doctors who have been shown to have difficulty making the diagnosis and on improving the treatment of identified patients.

Both traditional and atypical antipsychotics have been hypothesised to be effective in schizophrenia through limbic and cortical D2 dopamine receptor blockade.

To investigate this hypothesis with the D2/D3-selective positron emission tomography (PET) probe [76Br]-FLB457.

PETscans were performed on 6 controls and 18 patients with schizophreniatreated with haloperidol or with risperidone, clozapine, amisulpride or olanzapine.

The D2 dopamine receptor blockade was high in the temporal cortex with both haloperidol and atypical antipsychotics. The atypicals, however, induced a significantly lower D2 binding index than haloperidol in the thalamus and in the striatum.

Results suggest that cortical D2 dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D2 receptors in the cortex than in the basal ganglia is suggested as an indicator of favourable profile for a putative antipsychotic compound.

Obstetric complications have been studied frequently as possible risk factors for schizophrenia.

To test the hypotheses that individual obstetric complications are most strongly associated with an increased risk of schizophrenia in males, in patients with an early age at first diagnosis and in subjects with a maternal history of psychosis.

Cases of schizophrenia diagnosed between January 1971 and June 1994 were identified in the Stockholm County In-Patient Register. Controls were matched on age, gender, hospital of birth and parish of birth. Obstetric data were recorded blind to case–control status for 524 cases and 1043 controls.

This study did not find any large or consistent effect of gender, age at diagnosis or maternal history of psychosis on the risk of schizophrenia associated with individual complications.

Future studies should examine these effects using a much larger sample that includes patients with schizophrenia and control subjects whose genetic risk of schizophrenia has been assessed accurately.

Strong links exist between juvenile and adult depression, but comorbid conduct disorder may be associated with worse adult social difficulties.

To test the impact of comorbid conduct disorder on social adjustment and dysfunction, suicidality and criminality of adults who had had depression as youths.

Subjects (n=149) assessed at the Maudsley Hospital in 1970–1983 and meeting DSM–IV criteria for major depressive disorder with (CD–MDD; n=53) or without (MDD; n=96) conduct disorder were interviewed 20 years later. Data were collected on lifetime psychiatric disorders and adult social/personality functioning. Death certificates and criminal records were obtained.

The suicide risk was 2.45%, and 44.3% of the sample had attempted suicide once in their lives. Compared with the MDD group, the CD–MDD group had higher rates of suicidal behaviours and criminal offences, and exhibited more pervasive social dysfunction.

Adolescent depression is associated with raised risks of adult suicidality and with persistent interpersonal difficulties. Youths with CD–MDD show more severe and pervasive social dysfunction.

There is a paucity of information concerning the prevalence and detection of seasonal affective disorder (SAD) in UK populations.

To determine the prevalence, detection and current treatment of SAD within a general population sample.

The study was conducted in conjunction with the Outcomes of Depression International Network (ODIN) project, a large European study of depression. At the North Wales arm of the project, 1999 adults were randomly selected from a health authority database and screened by post for SAD with the Seasonal Patterns Assessment Questionnaire (SPAQ). Those scoring above cut-off were offered diagnostic interview, after which diagnosis of SAD according to DSM–IV criteria could be made.

The prevalence rate of SAD was calculated to be 2.4% (95% CI 1.4–1.3). The majority of identified cases had not previously received a diagnosis of SAD from their general practitioner, although over half had been diagnosed with other forms of depression and had been prescribed antidepressant medication.

Although SAD was found to be common in this general population sample it appeared to be largely underdiagnosed and/or misdiagnosed.

Although attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD) frequently co-occur, the underlying mechanisms for this comorbidity are not well understood.

To examine whether ADHD and conduct problems share common risk factors and whether ADHD+CD is a more heritable variant of ADHD.

Questionnaires were sent to 2846 families. Parent-rated data were obtained for 2082 twin pairs and analysed using bivariate genetic analysis and a liability threshold model approach.

The overlap of ADHD and conduct problems was explained by common genetic and non-shared environmental factors influencing both categories. Nevertheless, the two categories appeared to be partly distinct in that additional environmental factors influenced conduct problems. It appeared that ADHD+CD was a genetically more severe variant of ADHD.

Conduct problems and ADHD share a common genetic aetiology; ADHD+CD appears to be a more severe subtype in terms of genetic loading as well as clinical severity.

The clinical features of hyperphagic short stature (HSS) include short stature secondary to growth hormone insufficiency, excessive appetite (hyperphagia) and mild learning disabilities. Affected children characteristically live in conditions of high psychosocial stress. Symptoms resolve when the child is removed from the stressful environment. Family studies indicate a genetic predisposition.

To compare the behavioural and stress profiles of HSS with those of Prader–Willi syndrome (PWS), and to test the hypothesis that the genetic locus that predisposes to HSS co-inherits with the PWS locus at 15q11–13.

Twenty-five children with HSS, mean age 9.1 (s.d. 3.8) years, 28% female, were compared with 30 children with PWS, mean age 8.8 (s.d. 2.8) years, 33% female.

The clinical profiles were largely similar across the conditions, but no evidence was found in HSS of co-inheritance of the PWS critical region.

Hyperphagic short stature is one of the very few behavioural diseases associated with a pathognomonic physiological abnormality. Investigations of the suggested genetic dysregulation, which is so sensitive to environmental influences, may well be of importance in a broader context.

An association exists between smoking and schizophrenia, independent of other factors and related to psychotic symptomatology.

To determine whether smoking is associated with psychosis in bipolar affective disorder.

Smoking data were collected from 92 unrelated patients with bipolar affective disorder. An ordinal logistic regression analysis tested the relationship between smoking severity and psychotic symptomatology, allowing for potential confounders.

A significant relationship was detected between smoking/heavy smoking and history of psychosis (68.7%, n=44). Smoking was less prevalent in patients who were less symptomatic (56.5%, n=13) than in patients with a more severe psychosis (75.7%, n=31). Prevalence and severity of smoking predicted severity of psychotic symptoms (P=0.001), a relationship independent of other variables (P=0.0272).

A link between smoking and psychosis exists in bipolar affective disorder and may be independent of categorical diagnosis.

Few epidemiological studies have assessed the extent and nature of comorbid non-alcohol substance misuse in people with schizophrenia in the community in the UK.

To study the extent and nature of comorbid non-alcohol substance misuse in people with schizophrenia in central London.

Subjects were identified in an epidemiological census survey of South Westminster. Standardised assessment of each subject included demographic data, ratings of mental state and movement disorder and questioning about drug and alcohol misuse.

Individuals with schizophrenia or related psychoses were identified (n=352) and 57 (16%) reported a lifetime history of non-alcohol substance misuse. Age and gender were the main variables relevant to the extent and pattern of misuse. Self-reported non-alcohol substance misuse showed no significant relationship with a range of outcome measures.

The high proportion of subjects reporting non-alcohol substance misuse is comparable with figures from the USA. The reports of lifetime misuse most commonly referred to cannabis, psychostimulants, LSD, opiates and anticholinergics. Misuse was concentrated in those younger than 36 years and was reported more often by males.

Obsessive–compulsive disorder (OCD) is a disorder that appears to be underdiagnosed and undertreated, despite the evidence for effective treatments. There are variable estimates of OCD prevalence in the under-16s and published rates give little indication of age trends.

To establish the prevalence and associates of OCD in young people aged 5–15 years.

A nationwide (UK) epidemiological study of rates of psychiatric disorder in 5— to 15-year-olds (1999 British Child Mental Health Survey): 10 438 children were assessed.

Twenty-five children with OCD were identified (weighted overall prevalence 0.25%; 95% Cl 0.14–0.35), with prevalence rising exponentially with increasing age. Compared with normal controls, children with OCD were more likely to be from lower socio-economic class and of lower intelligence. Only three of these children had been seen by specialist children's services.

Although OCD is rare in young children, the rate increases towards the adult rates at puberty. Children with OCD have additional psychosocial disadvantage. The majority of the childhood cases identified in this survey appear to have been undetected and untreated.

Neuropsychological analyses of impulsiveness are needed to refine assessment of attention-deficit hyperactivity disorder (ADHD).

To investigate specific impairments in hyperactive children in a neuropsychological task battery of impulsiveness, the Maudsley Attention and Response Suppression (MARS) task battery, and to identify the neural substrates.

Impulsiveness was assessed using different tasks of inhibitory control and time management (MARS) in 55 children with ADHD, other diagnoses and controls. Functional magnetic resonance images were obtained from adolescents with and without ADHD during three of the tasks.

Children with ADHD, but not psychiatric controls, were impaired on tests of response inhibition, but not of motor timing. Reduced right prefrontal activation was observed in hyperactive adolescents during higher level inhibition and delay management, but not during simple sensorimotor coordination.

Attention-deficit hyperactivity disorder is characterised by specific deficits in tasks of motor response inhibition, but not motor timing, and by dysfunction of frontostriatal brain regions.

Relatively little is known about the relationships between psychiatric symptoms, diagnosis and psychosocial impairment.

To examine these contemporaneous relationships and prognostic significance in a large general population sample.

Symptoms of major depression, conduct and oppositional defiant disorders were assessed by interview in two waves of the Virginia Twin Study of Adolescent behavioural Development (2800 children aged 8–16 years).

Manychildren below the DSM–III–R diagnostic threshold, especially for depression, had symptom-related impairment, whereas many children reaching the symptom threshold for conduct and oppositional defiant disorders were little impaired. Impairment score was linearly related to symptom count, with no evidence of any additional impairment at the diagnostic threshold. For depression, only symptoms predicted later symptoms and diagnosis. For conduct and oppositional defiant disorders, impairment was additionally predictive of later symptoms and diagnosis.

Impairment, in addition to symptoms, is important for both nosology and prognosis.

Although a number of functional imaging studies are in agreement in suggesting orbitofrontal and subcortical hyperfunction in the pathophysiology of obsessive–compulsive disorder (OCD), the structural findings have been contradictory.

To investigate grey matter abnormalities in patients with OCD by employing a novel voxel-based analysis of magnetic resonance images.

Statistical parametric mapping was utilised to compare segmented grey matter images from 25 patients with OCD with those from 25 matched controls.

Increased regional grey matter density was found in multiple cortical areas, including the left orbitofrontal cortex, and in subcortical areas, including the thalamus. On the other hand, regions of reduction were confined to posterior parts of the brain, such as the left cuneus and the left cerebellum.

Increased grey matter density of frontal–subcortical circuits, consonant with the hypermetabolic findings from functional imaging studies, seems to exist in patients with OCD, and cerebellar dysfunction may be involved in the pathophysiology of OCD.

Although serotonin reuptake inhibitors are effective in panic disorder, questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain.

To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks.

Patients with panic disorder were randomised to placebo or to fluoxetine initiated at 10 mg daily for I week and then increased to 20 mg daily. The trial lasted 12 weeks, but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily.

Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point.

Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder. Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases.

Symptomatology in psychoses can be summarised as quantitative symptom dimensions, but their genetic basis is unknown.

To investigate whether genes make an important contribution to symptom dimensions.

A total of 224 probandwise twin pairs (106 monozygotic, 118 same-gender dizygotic) where probands had psychosis were ascertained from the Maudsley Twin Register in London. Factor analysis was performed on lifetime symptoms rated on the Operational Checklist for Psychotic Disorders (OPCRIT). Correlations of dimension scores within monozygotic and dizygotic pairs concordant for Research Diagnostic Criteria psychoses were performed. Relationships between dimension scores and genetic loading for psychoses were assessed using logistic regression.

Patterns of familial aggregation consistent with a genetic effect were found for the disorganised dimension and for some measures of the negative, manic and general psychotic dimensions. Disorganised dimension scores were related significantly to genetic loading for psychoses.

The disorganised dimension, and possibly other symptom dimensions, may be useful phenotypes for molecular genetic studies of psychoses.

Although weight and shape concerns are considered to be integral to the psychopathology of anorexia and bulimia nervosa, uncertainties remain about developmental aspects of the aetiology of these concerns and their relationship to eating disorders.

To review the recent literature on weight and shape concern, with particular emphasis on aetiology, to identify a possible developmental pathway from weight concern through abnormal eating behaviour to disorder.

Literature review of Medline and Psychlit databases using the keywords ‘eating disosrder’, ‘weight concern’, ‘shape concern’ and ‘aetiology’. Inclusion criteria were based on the strength of quantitative research findings, originality of ideas and recent publication.

Weight and shape concerns follow a developmental pathway arising before the typical age for the development of eating disorders. The origins are multifactorial, with biological, family and sociocultural features predominating.

Although weight and shape concern seems commonly to underlie the development of eating disorders, an alternative pathway appears to exist through impulsivity and fear of loss of control. Prevention strategies may usefully focus on the attitudes and concerns that lead to dieting behaviour.

Being born or living in urban areas is associated with high rates of schizophrenia. However, few studies have compared the incidence in urban/rural areas using the same methodology.

To compare service-based incidence rates for schizophrenia in rural Dumfries and Galloway in south-west Scotland with urban Camberwell in south-east London.

Using Research Diagnostic Criteria diagnoses from the OPCRIT computer algorithm, we compared the incidence of schizophrenia over 12 years (1979–1984 and 1992–1997) using indirect standardisation techniques and Poisson regression modelling.

The incidence was 61% higher in urban Camberwell than in rural Dumfries and Galloway (standardised incidence ratio (SIR)= 1.61; 95% Cl=1.42–1.81). There was no difference in incidence when we compared the White population in Camberwell with Dumfries and Galloway (SIR=1.12; 95% CI=0.86–1.43).

The incidence of schizophrenia in urban Camberwell was higher than that in rural Dumfries and Galloway; the high incidence of non-Whites in Camberwell largely explains the urban/rural difference.