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.

Diffusion tensor magnetic resonance imaging studies in schizophrenia to date have been largely inconsistent. This may reflect variation in methodology, and the use of small samples with differing illness duration and medication exposure.

To determine the extent and location of white matter microstructural changes in schizophrenia, using optimised diffusion tensor imaging in a large patient sample, and to consider the effects of illness duration and medication exposure.

Scans from 76 patients with schizophrenia and 76 matched controls were used to compare fractional anisotropy, a measure of white matter microstructural integrity, between the groups.

We found widespread clusters of reduced fractional anisotropy in patients, affecting most major white matter tracts. These reductions did not correlate with illness duration, and there was no difference between age-matched chronically and briefly medicated patients.

The finding of widespread fractional anisotropy reductions in our larger sample of patients with schizophrenia may explain some of the inconsistent findings of previous, smaller studies.

Risk factors for homicide are emerging; however, the predictive value of IQ, for which there is a strong prima facie case, has yet to be examined.

To examine the association between IQ and risk of death by homicide.

A cohort of 968 846 men, aged 18–19 years, were administered an IQ test battery at military conscription and then followed for mortality experience over two decades.

There were 191 deaths due to homicide during follow-up. In age-adjusted analyses, a high total IQ test score was associated with a reduced rate of homicide (hazard ratio (HR) per standard deviation increase in IQ score=0.49, 95% CI 0.42–0.57). A step-wise gradient was apparent across the three IQ groups (P-value for trend 50.001). After adjustment for indicators of socio-economic position and illness at conscription, this gradient was marginally attenuated (HR=0.57, 95% CI 0.49–0.67).

High IQ test scores in early adulthood were associated with a reduced risk of death by homicide.

Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking.

To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania.

Eighteen patients with DSM–IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry.

Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally.

Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.

Non-clinical psychotic symptoms appear common in children, but it is possible that a proportion of reported symptoms result from misinterpretation. There is a well-established association between pre-morbid low IQ score and schizophrenia. Psychosis-like symptoms in children may also be a risk factor for psychotic disorder but their relationship with IQ is unclear.

To investigate the prevalence, nature and frequency of psychosis-like symptoms in 12-year-old children and study their relationship with IQ.

Longitudinal study using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. A total of 6455 children completed screening questions for 12 psychotic symptoms followed by a semi-structured clinical assessment. IQ was assessed at 8 years of age using the Wechsler Intelligence Scale for Children (3rd UK edition).

The 6-month period prevalence for one or more symptoms was 13.7% (95% CI 12.8–14.5). After adjustment for confounding variables, there was a non-linear association between IQ score and psychosis-like symptoms, such that only those with below average IQ score had an increased risk of reporting such symptoms.

Non-clinical psychotic symptoms occur in a significant proportion of 12-year-olds. Symptoms are associated with low IQ and also less strongly with a high IQ score. The pattern of association with IQ differs from that observed in schizophrenia.

In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes.

To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point.

Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later.

There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition.

Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP.