In 1962 approximately 1.5 million French people living in Algeria were repatriated to France in very poor and often life-threatening conditions. These people constitute a cohort for the study of the long-term impact of gene–environment interaction on depression.

To examine the interaction between a highly stressful life event and subsequent depression, and its modulation by a length polymorphism of the serotonin transporter gene (5–HTTLPR).

A community sample of people aged 65 years and over residing in the Montpellier region of the south of France was randomly recruited from electoral rolls. Genotyping was performed on 248 repatriated persons and 632 controls. Current and lifetime major and minor depressive disorders were assessed according to DSM-IV criteria.

A significant relationship was observed between exposure to repatriation and subsequent depression (P<0.002), but there was no significant effect of gene alone (P = 0.62). After controlling for age, gender, education, disability, recent life events and cognitive function, the gene–environment interaction (repatriation×5-HTTLPR) was globally significant (P<0.002; OR = 3.21, 95% CI 2.48–5.12). Individuals carrying the two short (s) alleles of 5-HTTLPR were observed to be at higher risk (P<0.005; OR = 2.34, 95% CI 1.24–4.32), particularly when repatriation occurred before age 35 years (P<0.002; OR = 2.91, 95% CI 1.44–5.88), but this did not reach significance in those who were older at the time of the event (P = 0.067).

The association between depression and war repatriation was significantly modulated by 5-HTTLPR genotype but this appeared to occur only in people who were younger at the time of exposure.

No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.

To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.

Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance.

Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F=7.66, P=0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis.

These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

The Australian National Survey of Mental Health and Wellbeing conducted in 1997 and 2007 allows for exploration of changes in perceptions of mental healthcare. Major demographic, economic and health-behaviour changes have unfolded in Australia during this time. Governments also have increased spending on mental health services and been active in mental healthcare policy-making and implementation.

To compare rates of meeting of perceived need for mental healthcare between these two surveys dealing with adjustable sources of error.

Combined data-sets from 1997 and 2007 were analysed to provide weighted population estimates. Selection, indirect standardisation to a common reference population and multinomial logistic regression were employed, addressing bias and confounding.

Between 1997 and 2007 perceived need for information, counselling and skills training among people who consulted a general practitioner, psychiatrist, or psychologist for mental health reasons has increased. Within these service users, increases in perceived responses from services are evident among people who have perceived needs for information provision and counselling.

Policy and service changes are among possible causal explanations. Generally, trends are in the direction that policy changes were intended to achieve, giving some encouragement that these initiatives have had some effect. Reduced unmet perceived need suggests improved access to some interventions. However, the proportion of service responses to perceived need seen as sufficient is generally unchanged. This suggests the adequacy of treatments offered, as perceived by the Australian public, may not have improved and that a continued focus on quality of care is important for the future.

Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits.

To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving.

In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [11C]raclopride.

Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine.

The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.

Evidence suggests a role for oestrogen in depression but the involvement of oestrogen receptor polymorphisms remains unknown.

To determine the association between oestrogen receptor polymorphisms and late-life depression and the modifying effect of hormone treatment.

Depression was assessed using the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria and the Centre for Epidemiologic Studies – Depression Scale. The association between oestrogen receptor α and β (ER-α and ER-β) polymorphisms with severe depression was examined in 6017 community-dwelling elderly people using multivariate logistic regression.

In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-β rs1256049 increased the risk of depression, but only for non-current users of hormone treatment. In men, only the ER-β rs4986938 polymorphism showed a weak association with depression risk.

Oestrogen receptor polymorphisms are associated with severe late-life depression risk in women only.

About 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive–behavioural therapy (CBT).

To test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression.

Forty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150).

Adding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination.

This is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.

Anxiety is a common mental disorder among older people who live in the Western world, yet little is known about its prevalence in low- and middle-income countries.

We investigated the prevalence of anxiety and its correlates among older adults in low- and middle-income countries with diverse cultures.

Cross-sectional surveys of all residents aged 65 or over (n = 15 021) in 11 catchment sites in 7 countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico and Peru) were carried out as part of the 10/66 collaboration. Anxiety was measured by using the Geriatric Mental State Examination (GMS) and the Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT) diagnostic algorithm.

The age- and gender-standardised prevalence of anxiety varied greatly across sites, ranging from 0.1% (95% CI 0.0–0.3) in rural China to 9.6% (95% CI 6.2–13.1) in urban Peru. Urban centres had higher estimates of anxiety than their rural counterparts with adjusted (age, gender and site) odds ratios of 2.9 (95% CI 1.7–5.3). Age, gender, socioeconomic status and comorbid physical illnesses were all associated with a GMS/AGECAT diagnosis of anxiety, and so was disability (World Health Organization Disability Assessment Schedule II).

Anxiety is common in Latin America. Estimates from this region are similar to the ones from high-income European countries found in the literature. As demographic change will occur more rapidly in these countries, further research exploring the mental health of older people in developing areas is vital, with the inclusion of other specific anxiety disorders, along with evidence for strategies for supporting those with these disorders.

Carers of people with eating disorders report high levels of distress. In addition, carers' responses to the illness may perpetuate eating disorder symptoms. A cognitive interpersonal maintenance model of eating disorders is proposed and interventions for carers may improve well-being in both carers and patients.

To examine an interpersonal maintenance model of eating disorders, using a self-help intervention for carers.

A pre-test–post-test design was used with carers randomised into self-help or guided self-help, which included the Expert Carers Helping Others (ECHO) intervention. Carers' distress, well-being, proposed maintenance factors, and carer reports on the status of the patient were measured.

Carers' distress reduced and secondary outcomes improved. Improvement in carers' status and perceived improvements in patients were associated with reductions in expressed emotion and in accommodating and enabling behaviours. Self-help and guided self-help versions were comparable.

Changes in maintenance factors from the theoretical model were associated with a reduction in carers' distress and improvement in perceived patient functioning. Interventions which specifically target maintaining factors may be of benefit.

Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.

To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.

Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.

Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16–3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00–2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09–2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.

This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.

The aetiology of visual hallucinations is poorly understood in dementia with Lewy bodies. Pathological alterations in visual cortical excitability may be one contributory mechanism.

To determine visual cortical excitability in people with dementia with Lewy bodies compared with aged-matched controls and also the relationship between visual cortical excitability and visual hallucinations in dementia with Lewy bodies.

Visual cortical excitability was determined by using transcranial magnetic stimulation (TMS) applied to the occiput to elicit phosphenes (transient subjective visual responses) in 21 patients with dementia with Lewy bodies and 19 age-matched controls.

Phosphene parameters were similar between both groups. However, in the patients with dementia with Lewy bodies, TMS measures of visual cortical excitability correlated strongly with the severity of visual hallucinations (P = 0.005). Six patients with dementia with Lewy bodies experienced visual hallucination-like phosphenes (for example, seeing people or figures on stimulation) compared with none of the controls (P = 0.02).

Increased visual cortical excitability in dementia with Lewy bodies does not appear to explain visual hallucinations but it may be a marker for their severity.

Music therapy has previously been found to be effective in the treatment of depression but the studies have been methodologically insufficient and lacking in clarity about the clinical model employed.

To determine the efficacy of music therapy added to standard care compared with standard care only in the treatment of depression among working-age people.

Participants (n = 79) with an ICD–10 diagnosis of depression were randomised to receive individual music therapy plus standard care (20 bi-weekly sessions) or standard care only, and followed up at baseline, at 3 months (after intervention) and at 6 months. Clinical measures included depression, anxiety, general functioning, quality of life and alexithymia. Trial registration: ISRCTN84185937.

Participants receiving music therapy plus standard care showed greater improvement than those receiving standard care only in depression symptoms (mean difference 4.65, 95% CI 0.59 to 8.70), anxiety symptoms (1.82, 95% CI 0.09 to 3.55) and general functioning (–4.58, 95% CI −8.93 to −0.24) at 3-month follow-up. The response rate was significantly higher for the music therapy plus standard care group than for the standard care only group (odds ratio 2.96, 95% CI 1.01 to 9.02).

Individual music therapy combined with standard care is effective for depression among working-age people with depression. The results of this study along with the previous research indicate that music therapy with its specific qualities is a valuable enhancement to established treatment practices.

Bipolar disorder is complex and can be difficult to diagnose. It is often misdiagnosed as recurrent major depressive disorder.

We had three main aims. To estimate the proportion of primary care patients with a working diagnosis of unipolar depression who satisfy DSM–IV criteria for bipolar disorder. To test two screening instruments for bipolar disorder (the Hypomania Checklist (HCL–32) and Bipolar Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess whether individuals with major depressive disorder with subthreshold manic symptoms differ from those individuals with major depressive disorder but with no or little history of manic symptoms in terms of clinical course, psychosocial functioning and quality of life.

Two-phase screening study in primary care.

Three estimates of the prevalence of undiagnosed bipolar disorder were obtained: 21.6%, 9.6% and 3.3%. The HCL–32 and BSDS questionnaires had quite low positive predictive values (50.0 and 30.1% respectively). Participants with major depressive disorder and with a history of subthreshold manic symptoms differed from those participants with no or little history of manic symptoms on several clinical features and on measures of both psychosocial functioning and quality of life.

Between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder. The HCL–32 and BSDS screening questionnaires may be more useful for detecting broader definitions of bipolar disorder than DSM–IV-defined bipolar disorder. Subdiagnostic features of bipolar disorder are relatively common in primary care patients with unipolar depression and are associated with a more morbid course of illness. Future classifications of recurrent depression should include dimensional measures of bipolar symptoms.

There is controversy about the implications of relatively small average drug–placebo differences observed in randomised controlled trials of antidepressant medications.

To investigate whether efficacy is better understood as a large effect in a subgroup of patients.

The mixture model was used to identify patient subgroups (patients benefiting or not benefiting from treatment) to directly model the skewness of Montgomery–åsberg Depression Rating Scale (MADRS) scores at week 8.

The MADRS scores improved by 15.9 points (95% CI 15.2–16.6) among patients who benefited from treatment. The proportion of patients who benefited from escitalopram and not from placebo treatment was 19.5%, corresponding to a number needed to treat of 5.

This model gave a considerably better fit to the data than the analysis of covariance model in which all patients were assumed to benefit from treatment. The small average antidepressant–placebo difference obscures a much larger effect in a clinically meaningful subgroup of patients.

Valproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.

To compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice.

An observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006.

A total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59–2.16). The rate of psychiatric hospital admissions was increased for valproate v. lithium (HR = 1.33, 95% CI 1.18–1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40–2.48), a manic index episode (HR = 1.24, 95% CI 1.01–1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04–2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium.

In daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.

Submicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases.

To identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup.

A total of 567 children with ADHD aged 5–17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, <1% frequency) were defined from single nucleotide polymorphism data.

Copy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/ perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, χ2 = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability.

Large, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems.