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Mark Adams

Publications and source records attributed to Mark Adams.

2 recordsLinked to original sources

Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank (N=4446)

BackgroundPrevious 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, different scanners and imaging sequences may, however, obscure further anatomical differences.\n\nMethodsIn this study, we tested for differences in subcortical grey matter volume and white matter integrity between depressed individuals and controls in a large sample of subjects from the first data release of the UK Biobank imaging study of 4446 individuals, which used consistent diagnostic criteria at a single assessment centre, with a single MRI scanner and protocol.\n\nResultsWhilst we found no significant differences in subcortical volumes, we report significant reductions in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) ({beta} = -0.187, p = 0.017). We also report reductions in FA in association/commissural fibres ({beta} = -0.184, p = 0.019) and thalamic radiations ({beta} = -0.175, p = 0.027). Examining tracts individually, we report tract-specific FA reductions in the left superior longitudinal fasciculus ({beta} = -0.218, pcorrected = 0.012) and superior thalamic radiation ({beta} = -0.258, pcorrected = 0.010) in subjects with depression.\n\nConclusionsOur findings highlight the need for further large adequately-powered studies of depression and provide further evidence for disrupted white matter integrity in the disorder. Future studies would focus on exploring the typical neuro-phenotype in homogenous subgroups of depression.

Neuroscience

Genome-wide analysis of over 106,000 individuals identifies 9 neuroticism-associated loci

Neuroticism is a personality trait of fundamental importance for psychological wellbeing and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes and heterogeneity in the measurement of neuroticism. Here we report a genome-wide association study of neuroticism in 91,370 participants of the UK Biobank cohort and a combined meta-analysis which includes a further 7,197 participants from the Generation Scotland Scottish Family Health Study (GS:SFHS) and 8,687 participants from a Queensland Institute of Medical Research (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Forms Neuroticism scale. We found a SNP-based heritability estimate for neuroticism of approximately 15% (SE = 0.7%). Meta-analysis identified 9 novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (p = 1.28x10-15) spanning 4 Mb and containing at least 36 genes. Other associated loci included genes of interest on chromosome 1 (GRIK3, glutamate receptor ionotropic kainate 3), chromosome 4 (KLHL2, Kelch-like protein 2), chromosome 17 (CRHR1, corticotropin-releasing hormone receptor 1 and MAPT, microtubule-associated protein Tau), and on chromosome 18 (CELF4, CUGBP elav-like family member 4). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a large genetic correlation between neuroticism and MDD (0.64) and a smaller genetic correlation with schizophrenia (0.22) but not with bipolar disorder. Polygenic scores derived from the primary UK Biobank sample captured about 1% of the variance in trait liability to neuroticism. Overall, our findings confirm a polygenic basis for neuroticism and substantial shared genetic architecture between neuroticism and MDD. The identification of 9 new neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.

Genetics