A sex-specific genome-wide association study of depression phenotypes in UK Biobank.

There are marked sex differences in the prevalence, phenotypic presentation and treatment response for major depression. While genome-wide association studies (GWAS) adjust for sex differences, to date, no studies seek to identify sex-specific markers and pathways. In this study, we performed a sex-stratified genome-wide association analysis for broad depression with the UK Biobank total participants (N = 274,141), including only non-related participants, as well as with males (N = 127,867) and females (N = 146,274) separately.

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.

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale.

Background: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.

Methods: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD).

Polygenic risk scores for schizophrenia and major depression are associated with socio-economic indicators of adversity in two British community samples.

Schizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors.

Evaluation of physical health in an in-patient psychiatric rehabilitation setting.

Background: The mortality gap between patients with and without serious mental illness (SMI) is around 15-20 years. Here, we aim to identify some of the factors contributing to that gap via poor physical health and sub-optimal medical management.

Methods: We report the results of a detailed cross-sectional study of physical health parameters in an in-patient rehabilitation population in Scotland, including a consideration of concordance with guidelines and comparisons to healthy populations.

Local CpG density affects the trajectory and variance of age-associated DNA methylation changes.

Background: DNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease.

Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.

Background: Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life.

Prevalence and predictors of Motoric Cognitive Risk syndrome in a community-dwelling older Scottish population: A longitudinal observational study.

Objectives: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia.

Methods: In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.

Antidepressant use and risk of adverse outcomes: population-based cohort study.

Background: Antidepressants are one of the most widely prescribed drugs in the global north. However, little is known about the health consequences of long-term treatment.

Aims: This study aimed to investigate the association between antidepressant use and adverse events.

Interventions for the management of fatigue in adults with a primary brain tumour.

Background: Fatigue is a common and disabling symptom in people with a primary brain tumour (PBT). The effectiveness of interventions for treating clinically significant levels of fatigue in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 4, 2016.

Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987.

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood.

TeenCovidLife: a resource to understand the impact of the COVID-19 pandemic on adolescents in Scotland.

TeenCovidLife is part of Generation Scotland's CovidLife projects, a set of longitudinal observational studies designed to assess the psychosocial and health impacts of the COVID-19 pandemic. TeenCovidLife focused on how adolescents in Scotland were coping during the pandemic. As of September 2021, Generation Scotland had conducted three TeenCovidLife surveys.

Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing.

Comparing personalized brain-based and genetic risk scores for major depressive disorder in large population samples of adults and adolescents.

Background: Major depressive disorder (MDD) is a polygenic disorder associated with brain alterations but until recently, there have been no brain-based metrics to quantify individual-level variation in brain morphology. Here, we evaluated and compared the performance of a new brain-based 'Regional Vulnerability Index' (RVI) with polygenic risk scores (PRS), in the context of MDD. We assessed associations with syndromal MDD in an adult sample ( = 702, age = 59 ± 10) and with subclinical depressive symptoms in a longitudinal adolescent sample (baseline  = 3,825, age = 10 ± 1; 2-year follow-up  = 2,081, age = 12 ± 1).

Gene-Environment Correlation over Time: A Longitudinal Analysis of Polygenic Risk Scores for Schizophrenia and Major Depression in Three British Cohorts Studies.

Research suggests that both genetic and environmental risk factors are involved in the aetiology of schizophrenia (SCZ) and major depressive disorder (MDD). Importantly, environmental and genetic risk factors are often related as evidenced in gene-environment correlation (rGE), which describes the observation that genetic and environmental factors are associated with each other. It is understood that rGE gets stronger over time as individuals select their environments more actively based on their genetic propensities.

Systematic evaluation of machine learning algorithms for neuroanatomically-based age prediction in youth.

Application of machine learning (ML) algorithms to structural magnetic resonance imaging (sMRI) data has yielded behaviorally meaningful estimates of the biological age of the brain (brain-age). The choice of the ML approach in estimating brain-age in youth is important because age-related brain changes in this age-group are dynamic. However, the comparative performance of the available ML algorithms has not been systematically appraised.

Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation.

Background: Whilst genetic and environmental risk factors for schizophrenia (SCZ) and major depressive disorder (MDD) have been established, it is unclear whether exposure to environmental risk factors is genetically confounded by passive, evocative or active gene-environment correlation (rGE).

Study Objective: This study aims to investigate: (a) whether the genetic risk for SCZ/MDD in children is correlated with established environmental and psychosocial risk factors in two British community samples, the 1958 National Child Development Study (NCDS) and the Millennium Cohort Study (MCS), (b) whether these associations vary between both psychopathologies, and (c) whether findings differ across the two cohorts which were born 42 years apart.

Methods: Polygenic risk scores (PRS) from existing large genome-wide associations studies (GWAS) were applied to test the correlation between the child genetic risk for SCZ/MDD and known environmental risk factors.

Sexual dimorphism in the relationship between brain complexity, volume and general intelligence (g): a cross-cohort study.

Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence, but less is known about the sexual dimorphism of these relationships.

Sensory processing and eating behaviours in autism: A systematic review.

Objectives: The aim of this study was to assess the relationship between sensory processing and a broad range of eating behaviours across the lifespan.

Methods: Five electronic databases of published and unpublished quantitative studies were systematically searched, evaluated for risk of bias and synthesised according to identified eating outcomes.

Results: Across 25 studies, there was consistent evidence of a relationship between sensory processing and a range of eating behaviours.

Lessons from a catalogue of 6674 brain recordings.

It is now possible for scientists to publicly catalogue all the data they have ever collected on one phenomenon. For a decade, we have been measuring a brain response to visual symmetry called the sustained posterior negativity (SPN). Here we report how we have made a total of 6674 individual SPNs from 2215 participants publicly available, along with data extraction and visualization tools (https://osf.

Eye Movement Patterns Can Distinguish Schizophrenia From the Major Affective Disorders and Healthy Control Subjects.

Background And Hypothesis: No objective tests are currently available to help diagnosis of major psychiatric disorders. This study evaluates the potential of eye movement behavior patterns to predict schizophrenia subjects compared to those with major affective disorders and control groups.

Study Design: Eye movements were recorded from a training set of UK subjects with schizophrenia (SCZ;  = 120), bipolar affective disorder (BPAD;  = 141), major depressive disorder (MDD;  = 136), and healthy controls (CON;  = 142), and from a hold-out set of 133 individuals with proportional group sizes.