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

Xingxing Zhu,Rona J Strawbridge,Donald M Lyall,Daniel J Smith,Breda Cullen,Laura M Lyall,Joey Ward

doi:10.1038/s41398-021-01522-4

Xingxing Zhu, Rona J Strawbridge + Show 5 more

Open Access

https://doi.org/10.1038/s41398-021-01522-4

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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.

Highlights

Anhedonia, defined as subjectively diminished capacity to experience pleasure, is a transdiagnostic symptom present in several psychiatric disorders, such as major depressive disorder (MDD) and schizophrenia [1, 2]
We tested for associations between state anhedonia, PRS-anhedonia and brain structure and we examined the specificity of associations
For whole-brain measures, we found that state anhedonia was Derivation of polygenic risk scores for anhedonia The polygenic risk score for anhedonia was calculated using LDpred [30] based on the summary statistics from the genome-wide association studies (GWAS) of state anhedonia associated with reduced total grey matter volume (GMV) (β = −0.025, pcorrected < 0.001; Table S2) and increased total white matter volume (WMV) (β = 0.017, pcorrected < 0.001)

Summary

INTRODUCTION

Anhedonia, defined as subjectively diminished capacity to experience pleasure, is a transdiagnostic symptom present in several psychiatric disorders, such as major depressive disorder (MDD) and schizophrenia [1, 2]. Reductions in grey matter volume (GMV) and cortical thickness (CT) within several brain areas (including caudate, nucleus accumbens (NAcc), anterior cingulate cortex, prefrontal cortex and parietal lobe) have been reported in studies of trait anhedonia in patients with schizophrenia [11], in studies of negative symptoms of schizophrenia [12, 13], as well as in individuals with MDD [14]. Yang et al [18] found no correlation between state or trait anhedonia and prefrontal CT or parietal CT in healthy controls or subjects with MDD This inconsistency may be due to relatively small sample sizes (generally less than 100 [11, 13,14,15,16,17,18]) and both demographic and clinical heterogeneity within samples. NVQ or HND or HNC or equivalent: 1089 (6.11%) Other professional qualifications eg: nursing: 882 (5.08%)

METHODS AND MATERIALS

Findings

DISCUSSION