Recent meta-analyses have raised concerns about the replicability of gene × environment interactions involving the serotonin transporter gene (5-HTTLPR) in moderating the associations between adverse life events and mental disorders.

To use data gathered over the course of a 30-year longitudinal study of a New Zealand birth cohort to test the hypothesis that the presence of short (‘s’) alleles of 5-HTTLPR are associated with an increased response to life stress.

Participants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events.

A series of 104 regression models were fitted to four mental health outcomes (depressive symptoms, major depression, anxiety disorder and suicidal ideation) observed at ages 18, 21, 25 and 30 using 13 measures of life-course stress that spanned childhood and adult stressors. Both multiplicative and additive models were fitted to the data. No evidence was found that would support the hypothesis that ‘s' alleles of 5-HTTLPR are associated with increased responsivity to life stressors.

The present findings add to the evidence suggesting that it is unlikely that there is a stable gene × environment interaction involving 5-HTTLPR, life stress and mental disorders.

Epilepsy occurs in a significant minority of individuals with autism, but few long-term follow-up studies have been reported, so the prevalence, features (type of seizures, age at onset and severity, etc.) and correlates (IQ history of regression, family history) have only partially been identified.

To undertake a long-term follow-up study of individuals with autism in order to better characterise the features and correlates of epilepsy in individuals with autism.

One hundred and fifty individuals diagnosed with autism in childhood were followed up when they were 21+ years of age. All individuals were screened for a history of possible seizures by parental/informant questionnaire. An epilepsy interview was undertaken and medical notes reviewed for individuals with a history of possible seizures. The features and correlates of epilepsy were examined using survival and regression analysis.

Epilepsy developed in 22% of participants. In the majority, seizures began after 10 years of age. Generalised tonic–clonic seizures predominated (88%). In over a half (19/33), seizures occurred weekly or less frequently and in the majority of individuals (28/31) they were controlled with the prescription of one to two anticonvulsants. Epilepsy was associated with gender (female), intellectual disability and poorer verbal abilities. Although the presence of epilepsy in the probands was not associated with an increased risk of epilepsy in their relatives, it was associated with the presence of the broader autism phenotype in relatives. This indicates that the familial liability to autism was associated with the risk for epilepsy in the proband.

Epilepsy is an important medical complication that develops in individuals with autism. Seizures may first begin in adolescence or adulthood. Putative risk factors for epilepsy in autism were identified and these will require further investigation in future studies.

There is a need for a rapid-acting, non-injection, acute treatment for agitation.

To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia.

This phase III, randomised, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov number NCT00628589) enrolled 344 individuals who received one, two or three doses of inhaled loxapine (5 or 10 mg) or a placebo. Lorazepam rescue was permitted after dose two. The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale–Excited Component (PANSS–EC) 2 h after dose one. The key secondary end-point was Clinical Global Impression–Improvement scale (CGI–I) score 2 h after dose one.

Inhaled loxapine (5 and 10 mg) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points. Reduced PANSS–EC score was evident 10 min after dose one with both 5 and 10mg doses. Inhaled loxapine was well tolerated, and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications.

Inhaled loxapine provided a rapid, well-tolerated acute treatment for agitation in people with schizophrenia.

Concerns have been expressed about the impact that screening for risk of suicide may have on a person's mental health.

To examine whether screening for suicidal ideation among people who attend primary care services and have signs of depression increases the short-term incidence of feeling that life is not worth living.

In a multicentre, single-blind, randomised controlled trial, 443 patients in four general practices were randomised to screening for suicidal ideation or control questions on health and lifestyle (trial registration: ISRCTN84692657). The primary outcome was thinking that life is not worth living measured 10–14 days after randomisation. Secondary outcome measures comprised other aspects of suicidal ideation and behaviour.

A total of 443 participants were randomised to early (n = 230) or delayed screening (n = 213). Their mean age was 48.5 years (s.d. = 18.4, range 16–92) and 137 (30.9%) were male. The adjusted odds of experiencing thoughts that life was not worth living at follow-up among those randomised to early compared with delayed screening was 0.88 (95% CI 0.66–1.18). Differences in secondary outcomes between the two groups were not seen. Among those randomised to early screening, 37 people (22.3%) reported thinking about taking their life at baseline and 24 (14.6%) that they had this thought 2 weeks later.

Screening for suicidal ideation in primary care among people who have signs of depression does not appear to induce feelings that life is not worth living.

Little research has been conducted on the factors that may explain the higher rates of mental health problems in United States National Guard soldiers who have deployed to the Iraq War.

To examine whether financial hardship, job loss, employer support and the effect of deployment absence on co-workers were associated with depression and post-traumatic stress disorder (PTSD).

Cross-sectional data were obtained from 4034 National Guard soldiers at two time points. All measures were assessed by self-report.

The four factors were associated with depression and PTSD, with variability based on outcome and time point. For example, job loss increased the odds of meeting criteria for depression at 3 and 12 months and for PTSD at 12 months; the negative effect of deployment absence on co-workers increased the likelihood of meeting criteria for PTSD, but not depression, at both time points.

The findings demonstrate that National Guard soldiers have unique post-deployment social and material concerns that impair their mental health.

The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse.

To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes.

Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose.

Overall incidence was 3.01/100 000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year.

Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.

Mixed anxiety and depressive disorder (MADD) is common yet ill-defined, with little known about outcomes.

To determine MADD outcomes over 1 year.

We recruited 250 adults attending seven London general practices with mild–moderate distress. Three groups were defined using a diagnostic interview: MADD, other ICD–10 psychiatric diagnosis, no psychiatric diagnosis. We assessed symptoms of distress (General Health Questionnaire–28), quality of life (12-item Short Form Health Survey), general practitioner (GP) diagnosis and consultation rate at baseline, 3 months and 1 year.

Two-thirds of participants with MADD had no significant psychological distress at 3 months (61%) or 1 year (69%). However, compared with those with no diagnosis, individuals had twice the risk of significant distress (incidence rate ratio 2.39, 95% CI 1.29–4.42) at 3 months but not 1 year, and persistently lower quality of life (mental health functioning). There was no significant difference in GP consultation rate/diagnosis.

The majority with MADD improved, but individuals had an increased risk of significant distress at 3 months and a lower quality of life. As we cannot currently predict those with a poorer prognosis these patients should be actively monitored in primary care.

Examination of the brain regions that show aberrant activations and/or deactivations during semantic word generation could pave the way for a better understanding of the neurobiology of cognitive dysfunction in schizophrenia.

To examine the pattern of functional magnetic resonance imaging blood oxygen level dependent activations and deactivations during semantic word generation in schizophrenia.

Functional magnetic resonance imaging was performed on 24 participants with schizophrenia and 24 matched healthy controls during an overt, paced, ‘semantic category word generation’ condition and a baseline ‘word repetition’ condition that modelled all the lead-in/associated processes involved in the performance of the generation task.

The brain regions activated during word generation in healthy individuals were replicated with minimal redundancies in participants with schizophrenia. The individuals with schizophrenia showed additional activations of temporo-parieto-occipital cortical regions as well as subcortical regions, despite significantly poorer behavioural performance than the healthy participants. Importantly, the extensive deactivations in other brain regions during word generation in healthy individuals could not be replicated in those with schizophrenia.

More widespread activations and deficient deactivations in the poorly performing participants with schizophrenia may reflect an inability to inhibit competing cognitive processes, which in turn could constitute the core information-processing deficit underlying impaired word generation in schizophrenia.

There are concerns that the prevalence of mental disorder is increasing.

To determine whether the prevalence of common adult mental disorders has increased over time, using age–period–cohort analysis.

The study consisted of a pseudocohort analysis of a sequence of three cross-sectional surveys of the English household population. The main outcome was common mental disorder, indicated by a score of 12 or above on the Revised Clinical Interview Schedule (CIS-R). Secondary outcomes were neurotic symptoms likely to require treatment, indicated by a CIS-R score of 18 or over, and individual subscale scores for fatigue, sleep problems, irritability and worry.

There were 8670 participants in the 1993 survey, 6977 in the 2000 survey and 6815 in the 2007 survey. In men a significant increase in common mental disorder occurred between the cohort born in 1943–9 and that born in 1950–6 (odds ratio 1.4, 95% CI 1.1–1.9) but prevalence in subsequent cohorts remained largely stable. More extended increases in prevalence of sleep problems and mental disorders were observed in women, but not consistently across cohorts or measures.

We found little evidence that the prevalence of common mental disorder is increasing.

Evidence on cost-effectiveness is important to make well-informed decisions regarding care delivery.

To determine the balance between costs and health outcomes of cognitive–behavioural therapy (CBT) compared with treatment as usual (TAU) in people with schizophrenia who have persistent and recurrent symptoms of psychosis. Trial number: ISRCTN57292778.

A total of 216 people were randomised and followed up for 18 months. The primary clinical outcome measure was time functioning within the normal range. Normal functioning was defined as social functioning within the 95% range of the general population and no or minimal suffering and/or no or minimal affect on daily life of persistent psychotic symptoms. The difference in number of days was estimated. Using a societal perspective, cost differences were estimated and combined with clinical outcome to yield an incremental cost-effectiveness ratio (ICER). Uncertainty was accessed using bootstrapping and displayed by means of a cost-effectiveness acceptability curve.

In the CBT group, participants experienced 183 days of normal social functioning, whereas the TAU group experienced 106 days. The ICER was e47 per day of normal functioning gained. Cognitive–behavioural therapy implies higher costs, yet results in better health outcomes. Sensitivity analyses showed that targeting individuals who have not been hospitalised before receiving CBT results in an ICER of e14 per day normal functioning gained.

Days of normal functioning improved in the CBT condition compared with TAU, but this gain in health was associated with additional societal costs.

Schizophrenia is associated with often widespread changes in white matter structure. Most studies have investigated changes in fractional anisotropy, whereas alterations in radial or axial diffusivity have barely been investigated until now.

To investigate radial diffusivity as a potential marker of dysmyelination in direct relation to abnormalities in neural activation.

Neural activation in association with decision-making under uncertainty was investigated in 19 people with schizophrenia and 20 healthy controls and linked to radial diffusivity as measured by diffusion tensor imaging.

Decision-making under uncertainty was associated with a significantly decreased activation in a frontostriatocingulate network in the schizophrenia group. Structurally, they exhibited increased radial diffusivity in temporal white matter that was negatively correlated with activation in parts of the frontostriatocingulate network.

Present data indicate that altered diffusivity within relevant white matter networks may be closely linked to abnormal neural activation in schizophrenia.

The value of family psychoeducation for schizophrenia has been well established, and indications for its use have recently expanded to include bipolar affective disorder. However, no study to date has adequately examined its use in depression.

To examine family psychoeducation in the maintenance treatment of depression and to investigate the influence of the family's expressed emotion (EE) on its effectiveness.

Of 103 patients diagnosed with major depression and their primary family members, 57 pairs provided written informed consent. The pairs were randomly allocated to the intervention (n = 25) or control (n = 32). One family in the intervention group and two in the control group withdrew their consent after randomisation. The intervention group underwent four psychoeducation sessions consisting of didactic lectures about depression and group problem-solving focusing on how to cope in high-EE situations. Patients did not attend these sessions. Patients in both the intervention and control groups received treatment as usual. The families' EE levels were evaluated through Five-Minute Speech Samples. The primary outcome was relapse.

Time to relapse was statistically significantly longer in the psychoeducation group than in the control group (Kaplan–Meier survival analysis, P = 0.002). The relapse rates up to the 9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI 0.04–0.66; number needed to treat 2.4, 95% CI 1.6–4.9). In Cox proportional hazard analysis, baseline EE did not moderate the effectiveness of the intervention.

Family psychoeducation is effective in the prevention of relapse in adult patients with major depression.

Behavioural activation appears as effective as cognitive– behaviour therapy (CBT) in the treatment of depression. If equally effective, then behavioural activation may be the preferred treatment option because it may be suitable for delivery by therapists with less training. This is the first randomised controlled trial to look at this possibility.

To examine whether generic mental health workers can deliver effective behavioural activation as a step-three high-intensity intervention.

A randomised controlled trial (ISRCTN27045243) comparing behavioural activation (n = 24) with treatment as usual (n = 23) in primary care.

Intention-to-treat analyses indicated a difference in favour of behavioural activation of –15.79 (95% CI –24.55 to –7.02) on the Beck Depression Inventory–II and Work and Social Adjustment Scale (mean difference –11.12, 95% CI –17.53 to –4.70).

Effective behavioural activation appears suitable for delivery by generic mental health professionals without previous experience as therapists. Large-scale trial comparisons with an active comparator (CBT) are needed.

There has been little research into the prevalence of mental health problems in lesbian, gay and bisexual (LGB) people in the UK with most work conducted in the USA.

To relate the prevalence of mental disorder, self-harm and suicide attempts to sexual orientation in England, and to test whether psychiatric problems were associated with discrimination on grounds of sexuality.

The Adult Psychiatric Morbidity Survey 2007 (n = 7403) was representative of the population living in private UK households. Standardised questions provided demographic information. Neurotic symptoms, common mental disorders, probable psychosis, suicidality, alcohol and drug dependence and service utilisation were assessed. In addition, detailed information was obtained about aspects of sexual identity and perceived discrimination on these grounds.

Self-reported identification as non-heterosexual (determined by both orientation and sexual partnership, separately) was associated with unhappiness, neurotic disorders overall, depressive episodes, generalised anxiety disorder, obsessive–compulsive disorder, phobic disorder, probable psychosis, suicidal thoughts and acts, self-harm and alcohol and drug dependence. Mental health-related general practitioner consultations and community care service use over the previous year were also elevated. In the non-heterosexual group, discrimination on the grounds of sexual orientation predicted certain neurotic disorder outcomes, even after adjustment for potentially confounding demographic variables.

This study corroborates international findings that people of non-heterosexual orientation report elevated levels of mental health problems and service usage, and it lends further support to the suggestion that perceived discrimination may act as a social stressor in the genesis of mental health problems in this population.

Hypochondriasis, characterised by severe health anxiety, is a common condition associated with functional disability. Cognitive–behavioural therapy (CBT) is an effective but not widely disseminated treatment for hypochondriasis. Internet-based CBT, including guidance in the form of minimal therapist contact via email, could be a more accessible treatment, but no study has investigated internet-based CBT for hypochondriasis.

To investigate the efficacy of internet-based CBT for hypochondriasis.

A randomised controlled superiority trial with masked assessment comparing internet-based CBT (n = 40) over 12 weeks with an attention control condition (n = 41) for people with hypochondriasis. The primary outcome measure was the Health Anxiety Inventory. This trial is registrated with ClinicalTrials.gov (NCT00828152).

Participants receiving internet-based CBT made large and superior improvements compared with the control group on measures of health anxiety (between-group Cohen's d range 1.52–1.62).

Internet-based CBT is an efficacious treatment for hypochondriasis that has the potential to increase accessibility and availability of CBT for hypochodriasis.