Sleep disturbances comparable with insomnia occur in up to 80% of people with schizophrenia, but very little is known about the contribution of circadian coordination to these prevalent disruptions.

A systematic exploration of circadian time patterns in individuals with schizophrenia with recurrent sleep disruption.

We examined the relationship between sleep–wake activity, recorded actigraphically over 6 weeks, along with ambient light exposure and simultaneous circadian clock timing, by collecting weekly 48 h profiles of a urinary metabolite of melatonin in 20 out-patients with schizophrenia and 21 healthy control individuals matched for age, gender and being unemployed.

Significant sleep/circadian disruption occurred in all the participants with schizophrenia. Half these individuals showed severe circadian misalignment ranging from phase-advance/delay to non-24 h periods in sleep–wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production.

Severe circadian sleep/wake disruptions exist despite stability in mood, mental state and newer antipsychotic treatment. They cannot be explained by the individuals' level of everyday function.

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.

Depressive and anxiety disorders (common mental disorders) are the most common psychiatric condition encountered in primary healthcare.

To test the effectiveness of an intervention led by lay health counsellors in primary care settings (the MANAS intervention) to improve the outcomes of people with common mental disorders.

Twenty-four primary care facilities (12 public, 12 private) in Goa (India) were randomised to provide either collaborative stepped care or enhanced usual care to adults who screened positive for common mental disorders. Participants were assessed at 2, 6 and 12 months for presence of ICD-10 common mental disorders, the severity of symptoms of depression and anxiety, suicidal behaviour and disability levels. All analyses were intention to treat and carried out separately for private and public facilities and adjusted for the design. The trial has been registered with clinicaltrials.gov (NCT00446407).

A total of 2796 participants were recruited. In public facilities, the intervention was consistently associated with strong beneficial effects over the 12 months on all outcomes. There was a 30% decrease in the prevalence of common mental disorders among those with baseline ICD-10 diagnoses (risk ratio (RR) = 0.70, 95% CI 0.53–0.92); and a similar effect among the subgroup of participants with depression (RR = 0.76, 95% CI 0.59–0.98). Suicide attempts/plans showed a 36% reduction over 12 months (RR = 0.64, 95% CI 0.42–0.98) among baseline ICD-10 cases. Strong effects were observed on days out of work and psychological morbidity, and modest effects on overall disability. In contrast, there was little evidence of impact of the intervention on any outcome among participants attending private facilities.

Trained lay counsellors working within a collaborative-care model can reduce prevalence of common mental disorders, suicidal behaviour, psychological morbidity and disability days among those attending public primary care facilities.

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.

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.

This study compared the best available treatment for bulimia nervosa, cognitive–behavioural therapy (CBT) augmented by fluoxetine if indicated, with a stepped-care treatment approach in order to enhance treatment effectiveness.

To establish the relative effectiveness of these two approaches.

This was a randomised trial conducted at four clinical centres (Clinicaltrials.gov registration number: NCT00733525). A total of 293 participants with bulimia nervosa were randomised to one of two treatment conditions: manual-based CBT delivered in an individual therapy format involving 20 sessions over 18 weeks and participants who were predicted to be non-responders after 6 sessions of CBT had fluoxetine added to treatment; or a stepped-care approach that began with supervised self-help, with the addition of fluoxetine in participants who were predicted to be non-responders after six sessions, followed by CBT for those who failed to achieve abstinence with self-help and medication management.

Both in the intent-to-treat and completer samples, there were no differences between the two treatment conditions in inducing recovery (no binge eating or purging behaviours for 28 days) or remission (no longer meeting DSM–IV criteria). At the end of 1-year follow-up, the stepped-care condition was significantly superior to CBT.

Therapist-assisted self-help was an effective first-level treatment in the stepped-care sequence, and the full sequence was more effective than CBT suggesting that treatment is enhanced with a more individualised approach.

The neurobiological basis of personality is poorly understood. Frontotemporal lobar degeneration (FTLD) frequently presents with complex behavioural changes, and therefore potentially provides a disease model in which to investigate brain substrates of personality.

To assess neuroanatomical correlates of personality change in a cohort of individuals with FTLD using voxel-based morphometry (VBM).

Thirty consecutive individuals fulfilling consensus criteria for FTLD were assessed. Each participant's carer completed a Big Five Inventory (BFI) questionnaire on five key personality traits; for each trait, a change score was derived based on current compared with estimated premorbid characteristics. All participants underwent volumetric brain magnetic resonance imaging. A VBM analysis was implemented regressing change score for each trait against regional grey matter volume across the FTLD group.

The FTLD group showed a significant decline in extraversion, agreeableness, conscientiousness and openness and an increase in neuroticism. Change in particular personality traits was associated with overlapping profiles of grey matter loss in more anterior cortical areas and relative preservation of grey matter in more posterior areas; the most robust neuroanatomical correlate was identified for reduced conscientiousness in the region of the posterior superior temporal gyrus.

Quantitative measures of personality change in FTLD can be correlated with changes in regional grey matter. The neuroanatomical profiles for particular personality traits overlap brain circuits previously implicated in aspects of social cognition and suggest that dysfunction at the level of distributed cortical networks underpins personality change in FTLD.

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.

Depression is a common condition that has been frequently treated with psychotropics.

To review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.

A systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.

Six studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81–1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR = 1.06, 95% CI 0.65–1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.

There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.

Traditional perinatal practices may protect against postnatal common mental disorders (CMD) in non-Western societies.

To evaluate the association between perinatal practices and postnatal CMD in rural Ethiopia.

A population-based sample of 1065 women was followed up from pregnancy until 2 months postpartum. Qualitative investigation informed the development of scales measuring attitudes towards and adherence to perinatal practices. Postnatal CMD was measured using the Self-Reporting Questionnaire.

Endorsement of sociocultural perinatal practices was associated with lower odds of antenatal CMD persisting into the postnatal period (adjusted odds ratio (OR) = 0.66, 95% CI 0.45–0.95). Women who endorsed protective and celebratory perinatal practices but were unable to complete them had increased odds of incident (adjusted OR = 7.26, 95% CI 1.38–38.04) and persistent postnatal CMD (adjusted OR = 2.16, 95% CI 1.11–4.23) respectively.

There is evidence for an independent role of sociocultural practices in maintaining perinatal mental health in this Ethiopian community.

There is increasing evidence for genetic effects on the hypothalamic–pituitary axis system. More than one gene is likely to moderate corticoid-mediated activity.

To investigate whether the brain-derived neurotrophic factor (BDNF) polymorphism (rs6265, Val66Met) is associated with morning waking salivary cortisol and moderates the corticoid-mediated risk for subsequent depressive episode onset independently of the known effects of 5-HTTLPR (the serotonin transporter gene promoter).

High-risk adolescents (n = 401) were genotyped for Val66Met BDNF and 5-HTTLPR. Salivary samples were obtained on four consecutive school days within 1 h of waking. There were 365 (91%) remaining participants reassessed at 12 months for episodes of psychiatric disorder in the follow-up period. Of these, 357 (89%) had complete data for multivariate modelling.

There were 41 (11.2%) individuals who reported a new episode of clinical depression over the follow-up period. Increased risk for subsequent depression was found in carriers of the Val66Val genotype in BDNF with higher morning waking cortisol. This remained present when the known interaction between carriers of a short allele of 5-HTTLPR with higher morning salivary cortisol was taken into account.

Both BDNF and 5-HTTLPR genes show evidence of modifying the risk of a subsequent new depressive episode associated with elevated morning salivary cortisol. In adolescents morning salivary cortisol levels may constitute a biomarker for some forms of unipolar depression.

Early intervention services for psychosis aim to detect emergent symptoms, reduce the duration of untreated psychosis, and improve access to effective treatments.

To evaluate the effectiveness of early intervention services, cognitive–behavioural therapy (CBT) and family intervention in early psychosis.

Systematic review and meta-analysis of randomised controlled trials of early intervention services, CBT and family intervention for people with early psychosis.

Early intervention services reduced hospital admission, relapse rates and symptom severity, and improved access to and engagement with treatment. Used alone, family intervention reduced relapse and hospital admission rates, whereas CBT reduced the severity of symptoms with little impact on relapse or hospital admission.

For people with early psychosis, early intervention services appear to have clinically important benefits over standard care. Including CBT and family intervention within the service may contribute to improved outcomes in this critical period. The longer-term benefits of this approach and its component treatments for people with early and established psychosis need further research.

Transcultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia, but its influence on prognosis is unclear.

To investigate the relationship between insight, psychopathology and outcome of first-episode schizophrenia in Vellore, India.

Patients with a DSM–IV diagnosis of schizophrenia (η = 131) were assessed prospectively at baseline and at 6-month and 12-month follow-up. Demographic and clinical measures included insight, psychopathology, duration of untreated psychosis (DUP) and social functioning. Linear and logistic regression was used to measure predictors of outcome.

Follow-up data were available for 115 patients at 1 year. All achieved remission, half of them with and half without residual symptoms. Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome (relapse or functional impairment), controlling for baseline measures.

Outcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable, in line with other studies from low- and middle-income countries. Early improvement in insight might be a useful clinical guide to future outcome. Reduction of DUP should be a target for intervention.

There is evidence from North American trials that supported employment using the individual placement and support (IPS) model is effective in helping individuals with severe mental illness gain competitive employment. There have been few trials in other parts of the world.

To investigate the effectiveness and cost-effectiveness of IPS in the UK.

Individuals with severe mental illness in South London were randomised to IPS or local traditional vocational services (treatment as usual) (ISRCTN96677673).

Two hundred and nineteen participants were randomised, and 90% assessed 1 year later. There were no significant differences between the treatment as usual and intervention groups in obtaining competitive employment (13% in the intervention group and 7% in controls; risk ratio 1.35, 95% CI 0.95–1.93, P = 0.15), nor in secondary outcomes.

There was no evidence that IPS was of significant benefit in achieving competitive employment for individuals in South London at 1-year follow-up, which may reflect suboptimal implementation. Implementation of IPS can be challenging in the UK context where IPS is not structurally integrated with mental health services, and economic disincentives may lead to lower levels of motivation in individuals with severe mental illness and psychiatric professionals.

Little is known about the impact of life-threatening obstetric complications (‘near miss’) on women's mental health in low- and middle-income countries.

To examine the relationships between near miss and postpartum psychological distress in the Republic of Benin.

One-year prospective cohort using epidemiological and ethnographic techniques in a population of women delivering at health facilities.

In total 694 women contributed to the study. Except when associated with perinatal death, near-miss events were not associated with greater risk of psychological distress in the 12 months postpartum compared with uncomplicated childbirth. Much of the direct effect of near miss with perinatal death on increased risk of psychological distress was shown to be mediated through wider consequences of traumatic childbirth.

A live baby protects near-miss women from increased vulnerability by giving a positive element in their lives that helps them cope and reduces their risk of psychological distress. Near-miss women with perinatal death should be targeted early postpartum to prevent or treat the development of depressive symptoms.

Previous studies have suggested that impaired fetal and childhood growth are associated with an increased risk of schizophrenia, but the association of pre-adult growth with non-clinical psychotic symptoms (psychosis-like symptoms) in children is not known.

To explore the associations of body size at birth and age 7.5 years with childhood psychosis-like symptoms.

Prospective cohort of children followed up from birth to age 12: the ALSPAC cohort.

Data on 6000 singleton infants born after 37 weeks of gestation. A one standard deviation increase in birth weight was associated with an 18% reduction in the risk of definite psychosis-like symptoms after adjusting for age and gestation (Odds ratio (OR) = 0.82, 95% CI = 0.73–0.92, P = 0.001). This association was partly confounded by maternal anthropometry, smoking during pregnancy, socioeconomic status and IQ. A similar association was seen for birth length and psychosis-like symptoms, which disappeared after controlling for birth weight. There was little evidence for an association of 7-year height or adiposity with psychosis-like symptoms.

Measures of impaired fetal, but not childhood, growth are associated with an increased risk of psychosis-like symptoms in 12-year-olds.

Selective serotonin reuptake inhibitors (SSRIs) are typically thought to have a delay of several weeks in the onset of their clinical effects. However, recent reports suggest they may have a much earlier therapeutic onset. A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs.

To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces.

Twenty-six healthy volunteers were randomised to receive a single oral dose of citalopram (20 mg) or placebo. Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging.

Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo.

Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought.