Predicting remission following CBT for childhood anxiety disorders: a machine learning approach.

Background: The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models.

Methods: A machine learning approach was applied to predict anxiety disorder remission in a large sample of 2114 anxious youth (5-18 years).

Patterns of sub-optimal change following CBT for childhood anxiety.

Background: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment.

Methods: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up.

Fine-mapping genomic loci refines bipolar disorder risk genes.

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD.

Genetic architecture distinguishes tinnitus from hearing loss.

Tinnitus is a heritable, highly prevalent auditory disorder treated by multiple medical specialties. Previous GWAS indicated high genetic correlations between tinnitus and hearing loss, with little indication of differentiating signals. We present a GWAS meta-analysis, triple previous sample sizes, and expand to non-European ancestries.

Genetic Decomposition of the Heritable Component of Reported Childhood Maltreatment.

Background: Decades of research have shown that environmental exposures, including self-reports of trauma, are partly heritable. Heritable characteristics may influence exposure to and interpretations of environmental factors. Identifying heritable factors associated with self-reported trauma could improve our understanding of vulnerability to exposure and the interpretation of life events.

The United Kingdom Eating Disorders Genetics Initiative.

Objective: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide.

Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder.

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource.

General dimensions of human brain morphometry inferred from genome-wide association data.

Understanding the neurodegenerative mechanisms underlying cognitive decline in the general population may facilitate early detection of adverse health outcomes in late life. This study investigates genetic links between brain morphometry, ageing and cognitive ability. We develop Genomic Principal Components Analysis (Genomic PCA) to model general dimensions of brain-wide morphometry at the level of their underlying genetic architecture.

Common and rare variant associations with latent traits underlying depression, bipolar disorder, and schizophrenia.

Genetic studies in psychiatry have primarily focused on the effects of common genetic variants, but few have investigated the role of rare genetic variants, particularly for major depression. In order to explore the role of rare variants in the gap between estimates of single nucleotide polymorphism (SNP) heritability and twin study heritability, we examined the contribution of common and rare genetic variants to latent traits underlying psychiatric disorders using high-quality imputed genotype data from the UK Biobank. Using a pre-registered analysis, we used items from the UK Biobank Mental Health Questionnaire relevant to three psychiatric disorders: major depression (N = 134,463), bipolar disorder (N = 117,376) and schizophrenia (N = 130,013) and identified a general hierarchical factor for each that described participants' responses.

Assessing the Evidence for Causal Associations Between Body Mass Index, C-Reactive Protein, Depression, and Reported Trauma Using Mendelian Randomization.

Background: Traumatic experiences are described as the strongest predictors of major depressive disorder (MDD), with inflammation potentially mediating the association between trauma and symptom onset. However, several studies indicate that body mass index (BMI) exerts a large confounding effect on both inflammation and MDD.

Methods: First, we sought to replicate previously reported associations between these traits in a large subset of the UK Biobank, using regression models with C-reactive protein (CRP) and MDD and as the outcome variables in 113,481 and 30,137 individuals, respectively.

Factors associated with anxiety disorder comorbidity.

Background: Anxiety and depressive disorders often co-occur and the order of their emergence may be associated with different clinical outcomes. However, minimal research has been conducted on anxiety-anxiety comorbidity. This study examined factors associated with anxiety comorbidity and anxiety-MDD temporal sequence.

Risk factor profiles for depression following childbirth or a chronic disease diagnosis: case-control study.

Background: Progress towards understanding the aetiology of major depression is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity.

Aims: To compare risk factor profiles for three subgroups of major depression according to episode context.

Feasibility and application of polygenic score analysis to the morphology of human-induced pluripotent stem cells.

Genome-wide association studies have identified thousands of significant associations between genetic variants and complex traits. Inferring biological insights from these associations has been challenging. One approach attempted has been to examine the effects of individual variants in cellular models.

Editorial: Genome-wide Association Studies of Internalizing Symptoms: A Big Step on a Long Road.

Anxiety and depression are collectively the most common mental illnesses, affecting 15% of the world's population in any given year. Together, they account for the greatest global burden of ongoing disability of any disorder, mental or physical. They frequently emerge early in life as internalizing disorders in childhood or adolescence, and have long-lasting effects on mental wellbeing, acting as risk factors for mental illnesses in adulthood.

Exploring polygenic-environment and residual-environment interactions for depressive symptoms within the UK Biobank.

Substantial advances have been made in identifying genetic contributions to depression, but little is known about how the effect of genes can be modulated by the environment, creating a gene-environment interaction. Using multivariate reaction norm models (MRNMs) within the UK Biobank (N = 61294-91644), we investigate whether the polygenic and residual variance components of depressive symptoms are modulated by 17 a priori selected covariate traits-12 environmental variables and 5 biomarkers. MRNMs, a mixed-effects modelling approach, provide unbiased polygenic-covariate interaction estimates for a quantitative trait by controlling for outcome-covariate correlations and residual-covariate interactions.

Latent subtypes of manic and/or irritable episode symptoms in two population-based cohorts - ERRATUM.

Background: Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.

Aims: To identify groups of people with homogeneous clinical characteristics using symptoms of manic and/or irritable mood and explore differences between groups in diagnoses, functional outcomes.