Anhedonia, or the decreased ability to experience pleasure, is a cardinal symptom of major depression that commonly occurs within other forms of psychopathology. Supportive of long-held theory that anhedonia represents a genetically influenced vulnerability marker for depression, evidence from twin studies suggests that it is moderately-largely heritable. However, the genomic sources of this heritability are just beginning to be understood. In this review, we survey what is known about the genomic architecture underlying anhedonia and related constructs. We briefly review twin and initial candidate gene studies before focusing on genome-wide association study (GWAS) and polygenic efforts. As large samples are needed to reliably detect the small effects that typically characterize common genetic variants, the study of anhedonia and related phenotypes conflicts with current genomic research requirements and frameworks that prioritize sample size over precise phenotyping. This has resulted in few and underpowered studies of anhedonia-related constructs that have largely failed to reliably identify individual variants. Nonetheless, the polygenic architecture of anhedonia-related constructs identified in these studies has genetic overlap with depression and schizophrenia as well as related brain structure (e.g., striatal volume), providing important clues to etiology that may usefully guide refinement in nosology. As we await the accumulation of larger samples for more well-powered GWAS of reward-related constructs, novel analytic techniques that leverage GWAS summary statistics (e.g., genomic structural equation modeling) may currently be used to help characterize how the genomic architecture of anhedonia is shared and distinct from that underlying other constructs (e.g., depression, neuroticism, anxiety).
Keywords: Anhedonia; Brain; Depression; GWAS; Gene; Reward; Striatum.
© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.