Genetic variations might modify associations between schizophrenia and cannabis or tobacco use.

To examine whether variants within the cannabinoid receptor (CNR1) and α7 nicotinic receptor (CHRNA7) genes are associated with schizophrenia, and whether these effects vary according to cannabis or tobacco use. We also examined a putative interaction between cannabis and Val158Met within the catechol-O-methyltransferase gene (COMT).

Genotype effects of CHRNA7 and CNR1 were studied in a case–control sample of 750 individuals with schizophrenia and 688 controls, with interactions for these genes studied in small subsamples. A case-only design of 493 of the schizophrenia group was used to examine interactions between cannabis use and COMT.

There was no evidence of association between schizophrenia and CNR1 (OR=0.97, 95% CI 0.82–1.13) or CHRNA7 (OR=1.07, 95% CI 0.77–1.49) genotypes, or of interactions between tobacco use and CHRNA7, or cannabis use and CNR1 or COMT genotypes.

Neither CNR1 nor CHRNA7 variation appears to alter the risk of schizophrenia. Furthermore, our results do not support the presence of different effects of cannabis use on schizophrenia according to variation within COMT.

Evidence from cross-sectional studies suggests a link between cerebral age-related white matter changes and depressive symptoms in older people, although the temporal association remains unclear.

To investigate age-related white matter changes on magnetic resonance imaging (MRI) as an independent predictor of depressive symptoms at 1 year after controlling for known confounders.

In a pan-European multicentre study of 639 older adults without significant disability, MRI white matter changes and demographic and clinical variables, including cognitive scores, quality of life, disability and depressive symptoms, were assessed at baseline. Clinical assessments were repeated at 1 year.

Using logistic regression analysis, severity of white matter changes was shown to independently and significantly predict depressive symptoms at 1 year after controlling for baseline depressive symptoms, quality of life and worsening disability (P<0.01).

White matter changes pre-date and are associated with the development of depressive symptoms. This has implications for treatment and prevention of depression in later life.

Minority ethnic groups in the UK are reported to have a poor experience of mental health services, but comparative information is scarce.

To examine ethnic differences in patients' experience of community mental health services.

Trusts providing mental health services in England conducted surveys in 2004 and 2005 of users of community mental health services. Multiple regression was used to examine ethnic differences in responses.

About 27 000 patients responded to each of the surveys, of whom 10% were of minority ethnic origin. In the 2004 survey, age, living alone, detention and hospital admissions were stronger predictors of patient experience than ethnicity Self-reported mental health status had the strongest explanatory effect. In the 2005 survey, the main negative differences relative to the White British were for Asians.

Ethnicity had a smaller effect on patient experience than other variables. Relative to the White British, the Black group did not report negative experiences whereas the Asian group were most likely to respond negatively. However, there is a need for improvements in services for minority ethnic groups, including access to talking therapies and better recording of ethnicity.

Prevalence of physical comorbidity in severe mental illness is a significant public health concern, but comparative data in people with diagnoses other than schizophrenia are sparse.

To investigate the prevalence of metabolic disease and cardiovascular risk in people with severe mental illness treated with antipsychotics in the community.

Case – control study of 90 people treated with antipsychotics in the community and 92 age- and gender-matched controls. The prevalence of metabolic syndrome and 10-year cardiovascular risk were calculated.

People on antipsychotics had a significantly worse metabolic profile than controls (F=6.583, d.f. = 15,161, P<0.0001). Moreover, metabolic syndrome was more prevalent (OR=3.68, 95% CI 1.71–7.93, P=0.001), as was cardiovascular risk across a number of outcomes. These results are consistent across diagnostic groups.

People with severe mental illness treated with antipsychotics have excess metabolic dysfunction and heightened risk for cardiovascular disease.

Little is known about international variations in employment rates among people with schizophrenia or about the factors associated with employment in this disorder.

To describe employment patterns and the variables associated with working in an international sample of people with schizophrenia.

An analysis was made of baseline data from the European Schizophrenia Cohort study, a 2-year investigation of people with schizophrenia in contact with secondary services and living in France, Germany and the UK (n = 1208).

Participants were working in all sections of the job market. People who had a degree, were living with their families or had experienced only a single episode of illness were more likely to be working. A continuous illness course, more severe non-psychotic symptoms and drug misuse reduced the odds of employment. There were large variations between centres in employment rates, which were highest in the three German study sites. These differences persisted after adjustment for individual characteristics.

Local social contexts may be as important as individual or illness-related factors in explaining employment status.

The origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progress

To investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individuals

Participants consisted of two groups: controls (n = 17) and individuals at ultra-high risk for development of psychosis (n = 16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month interval

Both the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over time

These preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication

The point prevalence of mental ill-health among adults with intellectual disabilities is 40.9%, but its incidence is unknown.

To determine the incidence and possible predictors of mental ill-health.

Prospective cohort study to measure mental ill-health in adults with mild to profound intellectual disabilities.

Cohort retention was 70% (n=651). The 2-year incidence of mental ill-health was 16.3% (12.6% excluding problem behaviours, and 4.6% for problem behaviours) and the standardised incidence ratio was 1.87 (95%CI1.51 2.28). Factors related to incident mental ill-health have some similarities with those in the general population, but also important differences. Type of accommodation and support, previous mental ill-health, urinary incontinence, not having impaired mobility, more severe intellectual disabilities, adult abuse, parental divorce in childhood and preceding life events predicted incident ill-health; however, deprivation, other childhood abuse or adversity, daytime occupation, and marital and smoking status did not.

This is a first step towards intervention trials, and identifying sub-populations for more proactive measures. Public health strategy and policy that is appropriate for this population should be developed.

Exposure to childhood adversity may explain why only a minority of combatants exposed to trauma develop psychological problems.

To examine the association between self-reported childhood vulnerability and later health outcomes in a large randomly selected male military cohort.

Data are derived from the first stage of a cohort study comparing Iraq veterans and non-deployed UK military personnel. We describe data collected by questionnaire from males in the regular UK armed forces (n=7937).

Pre-enlistment vulnerability is associated with being single, of lower rank, having low educational attainment and serving in the Army. Pre-enlistment vulnerability is associated with a variety of negative health outcomes. Two main factors emerge as important predictors of ill health: a ‘family relationships’ factor reflecting the home environment and an ‘externalising behaviour’ factor reflecting behavioural disturbance.

Pre-enlistment vulnerability is an important individual risk factor for ill health in military men. Awareness of such factors is important in understanding post-combat psychiatric disorder.

The efficacy and safety of long-acting injectable risperidone have not been compared with those of an oral atypical antipsychotic.

To compare long-acting risperidone and oral olanzapine in 377 patients with DSM–IV schizophrenia or schizoaffective disorder.

Patients were randomised to receive long-acting risperidone (25 mg or 50 mg every 14 days) or olanzapine (5–20 mg/day).

In the 13-week phase, long-acting risperidone was at least as effective as (not inferior to) oral olanzapine. In the 12-month phase, significant improvements in the Positive and Negative Syndrome Scale (PANSS) total and factor scores from baseline to month 12 and end-point were seen in both groups of patients. Few patients discontinued treatment because of an adverse event.

Both treatments were efficacious and well tolerated.

Few studies have examined people with comorbid schizophrenia-spectrum personality disorder and antisocial personality disorder, a subgroup who may differ psychophysiologically and behaviourally from those with either condition alone.

To test whether individuals with both types of personality disorder are particularly characterised by reduced orienting and arousal and by increased criminal offending.

In a community adult sample, self-reported crime and skin conductance orienting were collected on four diagnostic groups: schizophrenia-spectrum personality disorder only; antisocial personality disorder only; comorbidity of the two disorders; and a control group.

The comorbid group showed significantly higher levels of criminal behaviour than the other three groups. They also showed reduced skin conductance orienting to neutral tones compared with the other groups, and significantly reduced arousal and orienting to significant stimuli compared with the control group.

Reduced orienting may reflect a neurocognitive attentional risk factor for both antisocial and schizotypal personality disorders that indirectly reflects a common neural substrate to these disorders.

As understanding of the pathobiology of schizophrenia increases, the challenge is to relate such measures to outcome at a functional level

To consider our current understanding of how neurobiological variables relate to functional outcome and might constitute outcome measures in their own right

Critical appraisal of recent evidence on structural and functional imaging, neurological evaluation, early neurodevelopmental indices, genomics, proteomics, metabolomics and apoptotic mechanisms in relation to outcome

Studies conducted prospectively from the first episode of schizophrenia are generating more reliable findings but currently lack predictive power. Prediction of transition from ‘high-risk’ status to first episode has proved somewhat more fruitful, but the gain has been modest and circumscribed

Our current level of understanding does not yet allow the generation of predictive models on an individual patient basis. Genomic and metabolomic studies hold particular potential for generating clinically meaningful ‘biomarkers’ but considerable further work is necessary

A bias to develop negative affect in response to daily life stressors may be an important depression endophenotype, but remains difficult to assess.

To assess this mood bias endophenotype, uncontaminated by current mood, in the course of daily life.

The experience samping method was used to collect multiple appraisals of daily life event-related stress and negative affect in 279 female twin pairs. Cross-twin, cross-trait associations between daily life mood bias and DSM – IV depression were conducted.

Probands whose co-twins were diagnosed with lifetime depression showed a stronger mood bias to stress than those with co-twins without such a diagnosis, independent of probands' current depressive symptoms and to a greater extent in monozygotic twins than in dizygotic twins.

Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.

Some questionnaire studies have shown increased mental health problems, including probable posttraumatic stress disorder (PTSD), in soldiers deployed to Iraq.

To test prospectively whether such problems change over time and whether questionnaires provide accurate estimates of deployment-related PTSD compared with a clinical interview.

Dutch infantry troops from three cohorts completed questionnaires before deployment to Iraq (n=479), and about 5 months (n=382, 80%) and 15 months (n=331, 69%) thereafter. Post-traumatic stress disorder was evaluated by questionnaire and clinical interview.

There were no group changes for general distress symptoms. The rates of PTSD for each cohort were 21, 4 and 6% based on questionnaires at 5 months. The deployment-related rates of PTSD based on the clinical interview were 4, 3 and 3%.

There was a specific effect of deployment on mental health for a small minority. Questionnaires eliciting stress symptoms gave substantial overestimations of the rate of PTSD.

Our understanding of anatomical differences in people with autistic-spectrum disorder, is based on mixed-gender or male samples.

To study regional grey-matter and white-matter differences in the brains of women with autistic-spectrum disorder.

We compared the brain anatomy of 14 adult women with autistic-spectrum disorder with 19 controls using volumetric magnetic resonance imaging and voxel-based morphometry Results Women with autistic-spectrum disorder had a smaller density bilaterally of grey matter in the frontotemporal cortices and limbic system, and of white matter in the temporal lobes (anterior) and pons. In contrast, they had a larger white-matter density bilaterally in regions of the association and projection fibres of the frontal, parietal, posterior temporal and occipital lobes, in the commissural fibres of the corpus callosum (splenium) and cerebellum (anterior lobe). Further, we found a negative relationship between reduced grey-matter density in right limbic regions and social communication ability.

Women with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms.

Duration of untreated psychosis (DUP) is considered an important predictor of short-term clinical outcome

To explore the evolution of the concept of DUP, synthesise the evidence for its predictive value, highlight the problems in measurement, and consider the potential pitfalls of using DUP as a measure of the effectiveness of early intervention services

A survey of recent literature was conducted

Several studies and two systematicreviews confirm that DUP has a robust but moderate effecton outcome in schizophrenia. Studies vary widely in how DUP is defined and measured, since identifying precise time points when psychosis emerges and remits is conceptually ambiguous and clinically difficult

Standardised measurement of DUP is a vital first step in allowing comparisons between studies. Duration of untreated psychosis is a relevant measure only of the early detection function of early intervention services

Growth abnormalities have been suggested as a precursor to schizophrenia, but previous studies have not assessed growth patterns using repeated measures.

To assess the association between early life/later childhood growth patterns and risk of schizophrenia.

Using prospectively collected data from a birth cohort (born 1959–1967), measurements of height, weight and body mass index (BMI) were analysed to compare growth patterns during early life and later childhood between 70 individuals with schizophrenia-spectrum disorder (SSD) and 7710 without.

For women, growth in the SSD group was approximately 1 cm/year slower during early life (P<0.01); no association was observed for men. Later childhood growth was not associated with SSD. Weight patterns were not associated with SSD, whereas slower change in BMI was observed among the SSD group during later childhood.

The association between slower growth in early life and schizophrenia in women suggests that factors responsible for regulating growth might be important in the pathogenesis of the disorder.

Many intervention programmes have attempted to reduce disruptive behaviour problems during early childhood to prevent maladjustment during adolescence and adulthood.

To assess the long-term impact and clinical significance of a 2-year multicomponent preventive intervention on criminal behaviour and academic achievement, using intention-to-treat analyses.

Targeted disruptive–aggressive boys considered to be at risk of later criminality and low school achievement (n=250), identified from a community sample (n=895), were randomly allocated to an intervention or a control group. The rest of the sample (n=645) served as the low-risk group. The intervention was multimodal and aimed at boys, parents and teachers. Official data measured both outcomes.

Significantly more boys in the intervention group (13%; P<0.05) completed high-school graduation and generally fewer (11%; P=0.06) had a criminal record compared with those allocated to the control group.

The results suggest that early preventive intervention for those at high risk of antisocial behaviour is likely to benefit both the individuals concerned and society.

Although people with schizophrenia display impaired abilities for consent, it is not known how much impairment constitutes incapacity.

To assess a method for determining the categorical capacity status of potential participants in schizophrenia research.

Expert-judgement validation of capacity thresholds on the sub-scales of the MacArthur Competence Assessment Tool – Clinical Research (MacCAT–CR) was evaluated using receiver operating characteristic (ROC) analysis in 91 people with severe mental illness and 40 controls.

The ROC areas under the curve for the understanding, appreciation and reasoning sub-scales of the MacCAT–CR were 0.94 (95% CI 0.88–0.99), 0.85 (95% CI 0.76–0.94) and 0.80 (95% CI 0.70–0.90). These findings yielded negative and positive predictive values of incapacity that can guide the practice of investigators and research ethics committees.

By performing such validation studies for a few categories of research with varying risks and benefits, it might be possible to create evidence-based capacity determination guidelines for most schizophrenia research.

Previous work suggests that the association between urbanicity and schizophrenia may be greatest in those with pre-existing vulnerability.

To test for synergism in risk of schizophrenia between population density and a combined exposure of poor premorbid social and cognitive functioning.

For 371 603 adolescent males examined by the Israeli Draft Board on social and cognitive functioning, data on population density of place of residence and later hospitalisation for schizophrenia were obtained from population-based registries.

There was an interaction between population density (five levels) and poor premorbid social and cognitive functioning (interaction χ2=4.6, P=0.032). The adjusted increase in cumulative incidence associated with one unit change in population density was 0.10% in the vulnerable group (95% CI 0.019–0.18, P=0.015), nine times larger than that in the non-vulnerable group (0.011%, 95% CI 0.0017–0.020, P=0.021).

Risk of schizophrenia may increase when people with a genetic liability to the disorder, expressed as poor social and cognitive functioning, need to cope with city life.

A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis

To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms

The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task

Number of action – recognition errors was associated with psychosis risk (OR linear trend over 3 levels: 1.12, 95% CI 1.04–1.20) and differential error rate was associated with the degree of delusional ideation in a dose–response fashion (OR linear trend over 3 levels: 1.13, 95% CI 1.00–1.26)

Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore