Key result
Anhedonia and high polygenic risk linked to reduced grey matter volume and altered reward regions.
Why the study?
Few studies have explored the association between genetic loading for anhedonia indexed by polygenic risk scores and structural brain imaging phenotypes.
Observational (n=19,592)
Yes
Effect estimate: β = -0.025
p-value: p=<0.001
Both state anhedonia and genetic risk for anhedonia are associated with structural brain alterations, particularly in reward-related circuits.
Anhedonia-linked brain changes may signal mood-related cardiac risk; leaves open causal links and clinical utility pending prospective data.
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.
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Zhu et al. (2021) conducted an observational in Anhedonia (n=19,592). State anhedonia and polygenic risk score for anhedonia vs. Lower anhedonia or lower polygenic risk was evaluated on Total grey matter volume (GMV) (β = -0.025, p=<0.001). State anhedonia and higher polygenic risk for anhedonia were significantly associated with reduced total grey matter volume, increased total white matter volume, and structural alterations in reward-related brain regions.
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