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Concept: Dysthymia

471

The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes.

Concepts: Randomized controlled trial, Schizophrenia, Major depressive disorder, Major depressive episode, Dysthymia, Depression, Suicide, Sickness behavior

204

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg b.i.d. (n=6) or placebo (n=2), and the third cohort 40 mg t.i.d. (n=6) or placebo (n=2). Twenty-four patients with MDD were recruited, with the diagnosis and severity confirmed through remote interviews. Eligible patients received NSI-189 or placebo for 28 days in an inpatient setting with assessments for safety, pharmacokinetics (PK) and efficacy. Outpatient follow-up visits were conducted until day 84 (±3). NSI-189 was relatively well tolerated at all doses, with no serious adverse effects. NSI-189 area under the curve increased in a dose-related and nearly proportional manner across the three cohorts, with a half-life of 17.4-20.5 h. The exploratory efficacy measurements, including Symptoms Of Depression Questionnaire (SDQ), Montgomery-Asberg Depression Scale (MADRS), Clinical Global Impressions-Improvement (CGI-I), and The Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ) showed a promising reduction in depressive and cognitive symptoms across all measures for NSI-189, with significant improvement in the SDQ and CPFQ, and a medium to large effect size for all measures. These improvements persisted during the follow-up phase. In summary, NSI-189 shows potential as a treatment for MDD in an early phase study. The main limitation of this preliminary study was the small sample size of each cohort.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.178.

Concepts: Sample size, Cognitive behavioral therapy, Bipolar disorder, Major depressive disorder, Seasonal affective disorder, Dysthymia, Depression, Types of psychological depression

176

Some 5%-15% of all women experience postpartum depression (PPD), which for many is their first psychiatric disorder. The purpose of this study was to estimate the incidence of postpartum affective disorder (AD), duration of treatment, and rate of subsequent postpartum AD and other affective episodes in a nationwide cohort of women with no prior psychiatric history.

Concepts: Cohort study, Childbirth, Mental disorder, Schizophrenia, Psychiatry, Dysthymia, Mental status examination, Postpartum depression

171

BACKGROUND: There is a significant treatment gap for patients with depression. A third of sufferers never seek help, and the vast majority of those who do only do so after considerable delay. Little is understood regarding poor help-seeking rates amongst people with depression, with existing research mainly focussed on the impact of barriers to treatment. The current study explored psychological factors affecting help-seeking behaviour in clinically depressed individuals. METHODS: Semi-structured interviews were conducted with 20 current or previously clinically depressed participants who either had or had not sought professional help. Thematic analysis was used to analyse results. RESULTS: The onset of depressive symptoms created conflict with participants' identity and personal goals. Delays in seeking help were primarily attributed to the desire to protect identity and goals from the threat of depressive symptoms. Participants used avoidance strategies to reduce the perceived threat of depressive symptoms on identity. These strategies interfered with help-seeking. Help-seeking was only undertaken once participants reached a point of acceptance and began to make concessions in their identity and goals, at which time they reduced their use of avoidance. CONCLUSIONS: Difficulties resolving conflict between identity and depressive symptoms may account for significant delays in seeking help for depression. The results have implications for predicting health behaviour and improving treatment uptake for depression, and may inform existing help-seeking models.

Concepts: Cognitive behavioral therapy, Bipolar disorder, Major depressive disorder, Seasonal affective disorder, Dysthymia, Types of psychological depression, Suicide, Leonard Cohen

161

The primary aim of the current study was to examine self-criticism as a potential mechanism mediating the relation between mothers' own childhood maltreatment history and changes in subsequent maternal efficacy beliefs in a diverse sample of low-income mothers with and without major depressive disorder. Longitudinal data were drawn from a larger randomized clinical trial evaluating the effectiveness of interpersonal psychotherapy for depression among low-income mothers and their 12-month-old infant. Results indicated that higher levels of maltreatment in childhood led mothers to hold more self-critical judgments in adulthood. Additionally, mothers who had experienced more extensive childhood maltreatment histories perceived themselves as less efficacious in their role as mother. Structural equation modeling indicated that self-criticism mediated the relationship between childhood maltreatment and mothers' decreased perceived competency in her maternal role from when her child was an infant to the more demanding toddler years. Finally, this relationship held over and above the influence of mothers' depressive diagnostic status. Directions for future research and the clinical implications of these findings are discussed.

Concepts: Clinical trial, Randomized controlled trial, Effectiveness, Efficacy, Cognitive behavioral therapy, Major depressive disorder, Dysthymia, Interpersonal psychotherapy

143

With a lifetime prevalence of 16.2%, major depressive disorder is the fifth biggest contributor to the disease burden in the United States.

Concepts: Disease, United States, Major depressive disorder, Prevalence, Dysthymia, Disease burden

100

Previous reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, scanners and imaging sequences may, however, obscure further anatomical differences. In this study, we tested for differences in subcortical grey matter volume (n = 1157) and white matter integrity (n = 1089) between depressed individuals and controls in the subset of 8590 UK Biobank Imaging study participants who had undergone depression assessments. Whilst we found no significant differences in subcortical volumes, significant reductions were found in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) (β = -0.182, p = 0.005). We also found reductions in FA in association/commissural fibres (β = -0.184, pcorrected = 0.010) and thalamic radiations (β = -0.159, pcorrected = 0.020). Tract-specific FA reductions were also found in the left superior longitudinal fasciculus (β = -0.194, pcorrected = 0.025), superior thalamic radiation (β = -0.224, pcorrected = 0.009) and forceps major (β = -0.193, pcorrected = 0.025) in depression (all betas standardised). Our findings provide further evidence for disrupted white matter integrity in MDD.

Concepts: Human brain, Hippocampus, Bipolar disorder, Major depressive disorder, Seasonal affective disorder, Dysthymia, Types of psychological depression, Subcortical ischemic depression

84

Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study.

Concepts: Genetics, United Kingdom, England, Schizophrenia, Major depressive disorder, Dysthymia, Primary care, Scotland

75

People with severe mental illness (SMI) - schizophrenia, bipolar disorder and major depressive disorder - appear at risk for cardiovascular disease (CVD), but a comprehensive meta-analysis is lacking. We conducted a large-scale meta-analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD-related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4-13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross-sectional studies (odds ratio, OR=1.53, 95% CI: 1.27-1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47-1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21-1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7-5.3) during a median follow-up of 8.4 years (range 1.8-30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60-1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30-1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26-2.14), congestive heart failure (HR=2.10, 95% CI: 1.64-2.70), and CVD-related death (HR=1.85, 95% CI: 1.53-2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD-related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs.

Concepts: Epidemiology, Medical statistics, Schizophrenia, Bipolar disorder, Major depressive disorder, Dysthymia, Suicide, Cardiovascular diseases

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Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 × 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics.

Concepts: Genetics, Cognitive behavioral therapy, Major depressive disorder, Dysthymia, Treatment for depression