Associations between polygenic risk for anhedonia and functional brain activity during reward processing

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Anhedonia is a core symptom in major mental disorders, yet its neurobiological and genetic bases remain poorly understood.
• Understanding the genetic contribution to anhedonia is crucial for developing targeted treatments.

Purpose of the Study:

• To investigate the impact of a polygenic risk score (PRS) for anhedonia on brain activation during reward and loss anticipation and feedback.
• To explore the relationship between PRS, brain structure, and anhedonia severity across different psychiatric groups.

Main Methods:

• Derived an anhedonia PRS from a large genome-wide association study (N=375,275) in a sample of 517 individuals (healthy controls, major depressive disorder, schizophrenia, bipolar disorder).
• Utilized functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task to measure brain activation.
• Correlated PRS with brain activation in reward-related regions, structural brain volumes, and anhedonia scores.

Main Results:

• Increased anhedonia PRS was associated with decreased activation in the bilateral putamen and left middle frontal gyrus during reward anticipation.
• Higher PRS correlated with reduced activation in the right caudate during reward feedback and in the left middle frontal gyrus during loss anticipation.
• Anhedonia PRS was linked to hyperactivity in the bilateral putamen and right caudate during loss feedback, and reduced activation in the left middle frontal gyrus during salience processing.

Conclusions:

• Genetic predisposition to anhedonia influences brain activation patterns in the striatum and prefrontal cortex.
• These findings underscore the role of these brain regions in the neurobiological pathways underlying anhedonia.
• The study did not find significant correlations between PRS and brain volume or anhedonia symptom severity.