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)

Abstract

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
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ward, Dr Joey and Lyall, Dr Laura and Cullen, Dr Breda and Zhu, Miss Xingxing and Smith, Professor Daniel and Strawbridge, Dr Rona and Lyall, Dr Donald
• 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: 2158-3188
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131		Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health
302957		Mental Health Data Pathfinder	Daniel Smith	Medical Research Council (MRC)	MC_PC_17217	HW - Mental Health and Wellbeing