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

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.