Neuroticism mediates the effect of P2RX7 on outcomes of mood disorders.

Background: We previously reported an association between P2RX7 variant rs208294, diagnosis, and the longitudinal course of mood disorders. Here, we test whether the personality trait neuroticism mediates the effect of P2RX7 on the course of mood disorders.

Methods: Patients with DSM-IV mood disorder (256 with major depressive disorder and 168 with bipolar disorder [BD]) were diagnosed with semistructured interviews, genotyped, and followed up for a median of 60 (range 6-83) months.

Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study.

Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown.

Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC).

A mega-analysis of genome-wide association studies for major depressive disorder.

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.

Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis.

Objectives: Evidence suggests that childhood maltreatment may negatively affect not only the lifetime risk of depression but also clinically relevant measures of depression, such as course of illness and treatment outcome. The authors conducted the first meta-analysis to examine the relationship between childhood maltreatment and these clinically relevant measures of depression.

Method: The authors conducted searches in MEDLINE, PsycINFO, and Embase for articles examining the association of childhood maltreatment with course of illness (i.

Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa.

Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an anterior cingulate cortex (ACC) conflict task, while masked subliminal food, aversive and neutral images were presented.

Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder.

Background: It has been proposed that non-steroidal anti-inflammatory drugs (NSAIDs) may interfere with the efficacy of antidepressants and contribute to treatment resistance in major depressive disorder (MDD). This effect requires replication and a test of whether it is specific to serotonin-reuptake inhibiting (SRI) antidepressants.

Method: We tested the effect of concomitant medication with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated for up to 12 weeks in the GENDEP study.

Biomarkers predicting treatment outcome in depression: what is clinically significant?

Aim: To extend to biomarker studies the consensus clinical significance criterion of a three-point difference in Hamilton Rating Scale for Depression.

Materials & Methods: We simulated datasets modeled on large clinical trials.

Results: In a typical clinical trial comparing active treatment and placebo, a difference of three Hamilton Rating Scale for Depression (HRSD) points at the end of treatment corresponds to 6.

Relative impact of maternal depression and associated risk factors on offspring psychopathology.

Background: In general, mothers with depression experience more environmental and family risk factors, and lead riskier lifestyles, than mothers who are not depressed.

Aims: To test whether the exposure of a child to risk factors associated with mental health adds to the prediction of child psychopathology beyond exposure to maternal depression.

Method: In 7429 mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children in the UK, maternal depression was assessed when the children were aged 1.

Gene-environment interaction in major depression and antidepressant treatment response.

Response to antidepressants is interindividually variable. It has been suggested that this variability is a direct consequence of etiological heterogeneity. Therefore, the same genes, environments, and gene-environment interactions implicated in different etiological pathways to depression may also predict response to treatment.

Early and delayed onset of response to antidepressants in individual trajectories of change during treatment of major depression: a secondary analysis of data from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study.

Objective: The timing and rate of improvement after the initiation of an antidepressant has implications for establishing the mechanism of antidepressant action and for answering the clinically relevant question of how long an appropriate trial of antidepressant medication should be. We explore the individual trajectories of relative change in depression severity to establish what proportion of individuals experience early and late onset of improvement.

Method: Longitudinal latent class analysis was applied in a secondary analysis of data obtained from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study.

Genome-wide association analysis of copy number variation in recurrent depressive disorder.

Large, rare copy number variants (CNVs) have been implicated in a variety of psychiatric disorders, but the role of CNVs in recurrent depression is unclear. We performed a genome-wide analysis of large, rare CNVs in 3106 cases of recurrent depression, 459 controls screened for lifetime-absence of psychiatric disorder and 5619 unscreened controls from phase 2 of the Wellcome Trust Case Control Consortium (WTCCC2). We compared the frequency of cases with CNVs against the frequency observed in each control group, analysing CNVs over the whole genome, genic, intergenic, intronic and exonic regions.

Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression.

Background: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes.

Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms.

Background: Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.

Method: We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre.

CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP.

In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.

Poor decision making in male patients with anorexia nervosa.

Objective: Decision making is impaired in female patients with anorexia nervosa (AN), but it is unclear if the same impairment is present in male patients with AN.

Method: Decision making was assessed in 48 AN individuals (19 male and 29 female patients) and 61 healthy controls (20 male and 41 female patients) using the Iowa Gambling Task (IGT).

Results: Both male and female patients with AN performed significantly worse than healthy controls on the IGT.

Differential neural responses to food images in women with bulimia versus anorexia nervosa.

Background: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

The contribution of prenatal and postnatal maternal anxiety and depression to child maladjustment.

Background: The adverse effect of both pre- and post-natal maternal anxiety and depression on the development of offspring is shown by a large body of research. No published studies, however, have simultaneously: (i) controlled for co-occurring prenatal risks that may influence maternal prenatal anxiety and depression; (ii) compared the relative contributions of prenatal and postnatal maternal anxiety and depression on child functioning; and (iii) assessed a full range of child psychopathology and functioning to determine the relative effects of prenatal and postnatal anxiety and depression in the mother.

Method: Using 3,298 mother-offspring pairs, the authors examined these factors in a single-path analytic model.

Reactivity of affect and self-esteem during remission in bipolar affective disorder: an experimental investigation.

Background: Bipolar affective disorder (BPAD) is characterised by a lifelong vulnerability to develop episodes of depressed or elevated mood in response to stressful life events involving achievement or failure. We hypothesised that this latent vulnerability can manifest as reactivity of affect and self-esteem to experimentally induced experiences of success and failure and is shaped by history of childhood adversity.

Methods: Twenty-four people with remitted BPAD and twenty-four healthy controls underwent anagram-solving tasks designed to generate experiences of success and failure in two separate sessions.

Genes, environment, and individual differences in responding to treatment for depression.

A principal weakness of evidence-based psychiatry is that it does not account for the individual variability in therapeutic response among individuals with the same diagnosis. The aim of personalized psychiatry is to remediate this shortcoming and to use predictors to select treatment that is most likely to be beneficial for an individual. This article reviews the evidence that genetic variation, environmental exposures, and gene-environment interactions shape mental illness and influence treatment outcomes, with a primary focus on depression.

The truth about genetic variation in the serotonin transporter gene and response to stress and medication.

The question of whether a functional variant in the promoter of the serotonin transporter gene (5-HTTLPR) influences response to adversity and/or antidepressants has generated great interest and controversy. A review of the literature suggests that the issue is complicated by differences in methodology and sample ethnicity. When these confounders are accounted for, there probably is a real, if small, effect of 5-HTTLPR on response to both serotonin reuptake inhibitors and environmental adversity.

Depressive disorder moderates the effect of the FTO gene on body mass index.

There is evidence that obesity-related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to body mass index (BMI) in two independent samples of major depressive disorder (MDD) cases and controls.

Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: replications and implications for resolving inconsistent results.

Background: Genetic and environmental factors shape life-long vulnerability to depression, but most gene-environment interaction (G×E) research has focused on cross-sectional assessments rather than life-course phenotypes. This study tests the hypothesis that the G×E involving the length polymorphism in the serotonin-transporter-gene-linked-promoter-region (5-HTTLPR) and childhood maltreatment is specific to depression that runs a persistent course in adulthood.

Methods: The hypothesis is tested in two cohorts.