The source of variability in people's response to stressful life events is poorly understood.

We examine the genetic and environmental underpinning of resilience (i.e. the difference between the twins' internalising symptoms and their predicted symptoms based on cumulative stressful life events).

Stressful life event exposure and internalising symptoms were assessed at two time points in 7500 adult twins. Using the residual between actual and predicted internalising symptom total score, twin modelling was conducted for each wave separately and longitudinally.

Resilience was found to have a moderate genetic heritability at each wave (~31%). Qualitative gender effects were found. Incorporating error of measurement into the model increased the estimated heritability for the latent construct of resilience (~50%). When measurement error and occasion-specific effects were removed, environmental influences contributed roughly equally to level of resilience.

Both genes and environment influence level of psychiatric resilience, and are largely stable over time. Environmental influences can have an enduring effect on resilience.

Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful.

To systematically review randomised controlled trial evidence regarding non-pharmacological interventions.

We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES).

Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3–1.8) and for up to 6 months afterwards (SES range 0.2–2.2). Activities and music therapy by protocol (SES range 0.5–0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy.

There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes.

Caregivers make a significant and growing contribution to the social and medical care of people with long-standing disorders. The effective provision of this care is dependent on their own continuing health.

To investigate the relationship between weekly time spent caregiving and psychiatric and physical morbidity in a representative sample of the population of England.

Primary outcome measures were obtained from the Adult Psychiatric Morbidity Survey 2007. Self-report measures of mental and physical health were used, along with total symptom scores for common mental disorder derived from the Clinical Interview Schedule – Revised.

In total, 25% (n = 1883) of the sample identified themselves as caregivers. They had poorer mental health and higher psychiatric symptom scores than non-caregivers. There was an observable decline in mental health above 10 h per week. A twofold increase in psychiatric symptom scores in the clinical range was recorded in those providing care for more than 20 h per week. In adjusted analyses, there was no excess of physical disorders in caregivers.

We found strong evidence that caregiving affects the mental health of caregivers. Distress frequently reaches clinical thresholds, particularly in those providing most care. Strategies for maintaining the mental health of caregivers are needed, particularly as demographic changes are set to increase involvement in caregiving roles.

Between 30 and 60% of adults with unipolar or bipolar disorders exhibit impairments across multiple domains. However, little is known about impaired functioning in youth with mood disorders.

To examine the prevalence of objective, subjective and observer-rated disability in a large, representative sample of young people with a primary mood disorder.

Individuals aged 16–25 years presenting to youth mental health services for the first time with a primary mood disorder participated in a systematic diagnostic and clinical assessment. Impairment was assessed using objective (unemployment or disability payments), observer- (Social and Occupational Functioning Assessment Scale; SOFAS) and self-rated measures (role functioning according to the Brief Disability Questionnaire).

Of 1241 participants (83% unipolar; 56% female), at least 30% were functionally impaired on the objective, self-rated and/or observer-rated measures, with 16% impaired according to all three criteria. Even when current distress levels were taken into account, daily use of cannabis and/or nicotine were significantly associated with impairment, with odds ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders were related to lower SOFAS scores (OR = 2–5).

Levels of disability were significant, even in those presenting for mental healthcare for the first time. Functional impairment did not differ between unipolar and bipolar cases, but some evidence suggested that females with bipolar disorder were particularly disabled. The prevalence of comorbid disorders (50%) and polysubstance use (28%) and their association with disability indicate that more meaningful indicators of mood episode outcomes should focus on functional rather than symptom-specific measures. The association between functioning and nicotine use requires further exploration.

Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD).

To examine the effects of medication, placebo and supportive care on treatment outcome, and the relationships of expectations and therapeutic alliance to improvement.

A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were measured (trial registration at ClinicalTrials.gov: NCT00200902).

Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrolment predicted only placebo response.

Pill treatment yielded better outcome than supportive care alone. Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment, suggesting that they were shaped by prior experiences outside the clinical trial.

Pathways from early-life conduct problems to young adult depression remain poorly understood.

To test developmental pathways from early-life conduct problems to depression at age 18.

Data (n = 3542) came from the Avon Longitudinal Study of Parents and Children (ALSPAC). Previously derived conduct problem trajectories (ages 4–13 years) were used to examine associations with depression from ages 10 to 18 years, and the role of early childhood factors as potential confounders.

Over 43% of young adults with depression in the ALSPAC cohort had a history of child or adolescent conduct problems, yielding a population attributable fraction of 0.15 (95% CI 0.08–0.22). The association between conduct problems and depression at age 18 was considerable even after adjusting for prior depression (odds ratio 1.55, 95% CI 1.24–1.94). Early-onset persistent conduct problems carried the highest risk for later depression. Irritability characterised depression for those with a history of conduct problems.

Early-life conduct problems are robustly associated with later depressive disorder and may be useful targets for early intervention.

Alterations in the dopaminergic reward system, predominantly the striatum, constitute core characteristics of schizophrenia.

Functional connectivity of the dorsal striatum during reward-related trial-and-error learning was investigated in 17 people with schizophrenia and 18 healthy volunteers and related to striatal grey matter volume and psychopathology.

We used voxel-based morphometry and psychophysiological interaction to examine striatal volume and connectivity.

A reduced functional connectivity between left striatum and temporo-occipital areas, precuneus and insula could be detected in the schizophrenia group. The positive correlation between grey matter volume and functional connectivity of the left striatum yielded significant results in a very similar network. Connectivity of the left striatum was negatively correlated with negative symptoms.

Present results suggest a disruption in striatal functional connectivity that is closely linked to grey matter morphometry of the striatum. Decreased connectivity between the striatum and psychopathologically relevant networks may explain the emergence of negative symptoms.

Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function.

To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function.

Using 3 T magnetic resonance imaging we scanned 100 persons aged 19–82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape.

There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group×age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function.

Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

Limited research is focused on suicides in children aged below 15 years.

To analyse worldwide suicide rates in children aged 10–14 years in two decades: 1990–1999 and 2000–2009.

Suicide data for 81 countries or territories were retrieved from the World Health Organization Mortality Database, and population data from the World Bank data-set.

In the past two decades the suicide rate per 100 000 in boys aged 10–14 years in 81 countries has shown a minor decline (from 1.61 to 1.52) whereas in girls it has shown a slight increase (from 0.85 to 0.94). Although the average rate has not changed significantly, rates have decreased in Europe and increased in South America. The suicide rates remain critical for boys in some former USSR republics.

The changes may be related to economic recession and its impact on children from diverse cultural backgrounds, but may also be due to improvements in mortality registration in South America.

Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue.

To investigate whether higher BMI increases the risk of major depression.

Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case–control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI.

Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient −0.03, 95% CI −0.18 to 0.13, P = 0.73; GRS: coefficient −0.02, 95% CI −0.11 to 0.07, P = 0.62).

Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Depression is common and the efficacy of antidepressants is suboptimal. High plasma homocysteine has been consistently associated with depression, and treatment with certain B vitamins demonstrably reduces its concentration.

To determine whether vitamins B6, B12 and folic acid enhance response to antidepressant treatment over 52 weeks.

Randomised, double-blind, placebo-controlled trial of citalopram (20–40 g) together with 0.5mg of vitamin B12, 2mg of folic acid and 25mg of vitamin B6 for 52 weeks (Australian and New Zealand Clinical Trials Registry: 12609000256279). Participants were community-dwelling adults aged 50 years or over with DSM-IV-TR major depression. We measured severity of symptoms with the Montgomery–åsberg Depression Rating Scale (MADRS). The primary outcome was remission of the depressive episode after 12, 26 and 52 weeks. Secondary outcomes included reduction of MADRS scores over time and relapse of major depression after recovery by week 12.

In total, 153 people were randomised (76 placebo, 77 vitamins). Remission of symptoms was achieved by 78.1 and 79.4% of participants treated with placebo and vitamins by week 12 (P = 0.840), by 76.5 and 85.3% at week 26 and 75.8 and 85.5% at week 52 (effect of intervention over 52 weeks: odds ratio (OR) = 2.49, 95% CI 1.12–5.51). Group differences in MADRS scores over time were not significant (P = 0.739). The risk of subsequent relapse among those who had achieved remission of symptoms at week 12 was lower in the vitamins than placebo group (OR = 0.33, 95% CI 0.12–0.94).

B vitamins did not increase the 12-week efficacy of antidepressant treatment, but enhanced and sustained antidepressant response over 1 year. Replication of these findings would mandate that treatment guidelines adopt the adjunctive use of B vitamins as a safe and inexpensive strategy to manage major depression in middle-aged and older adults.

Early identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode.

To explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode.

A total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode.

At baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (P<0.001 and P = 0.02 respectively) and plasma levels (P = 0.002 and P = 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree).

Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.

Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned.

To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.

Nationwide Swedish quasi-experimental, family-based study following cohorts born 1989–1993 (ntotal = 526 167, ncousins = 262 267, nsiblings = 216 424) between the ages of 15 and 21 years.

Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23–7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44–2.03). Similar pattern of effects was found for substance misuse.

There were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.