Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank

Zhu, X., Ward, J. , Cullen, B. , Lyall, D. M. , Strawbridge, R. J. , Lyall, L. M. and Smith, D. J. (2021) Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank. Translational Psychiatry, 11, 395. (doi: 10.1038/s41398-021-01522-4) (PMID:34282121) (PMCID:PMC8289859)

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Anhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations in brain structure. Genome-wide association studies suggest that anhedonia is heritable, with a polygenic architecture, but few studies have explored the association between genetic loading for anhedonia—indexed by polygenic risk scores for anhedonia (PRS-anhedonia)—and structural brain imaging phenotypes. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Zhu, Xingxing and Cullen, Dr Breda and Ward, Dr Joey and Strawbridge, Dr Rona and Lyall, Dr Donald and Lyall, Dr Laura
Authors: Zhu, X., Ward, J., Cullen, B., Lyall, D. M., Strawbridge, R. J., Lyall, L. M., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
Journal Name:Translational Psychiatry
Publisher:Springer Nature
ISSN (Online):2158-3188
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Translational Psychiatry 11: 395
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health
302957Mental Health Data PathfinderDaniel SmithMedical Research Council (MRC)MC_PC_17217HW - Mental Health and Wellbeing