Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Altered dopamine transmission is linked to mental disorders like ADHD, schizophrenia, and depression.
• Reward system dysfunction may mediate this link.
• The COMT Val(158)Met polymorphism's role in gene-environment interactions (GxE) on reward processing requires clarification.

Purpose of the Study:

• To investigate the impact of the COMT Val(158)Met polymorphism interacting with environmental variation (GxE) on neuronal activity during reward processing.
• To clarify the genetic and environmental factors influencing reward system function.

Main Methods:

• 168 healthy young adults from a 25-year prospective study.
• Simultaneous EEG-fMRI during a monetary incentive delay task.
• COMT gene genotyping and assessment of childhood family adversity (CFA).

Main Results:

• Gene-environment interaction (GxE) showed increased fMRI reward-related activation with higher CFA in Met homozygotes.
• Val/Met heterozygotes and Val homozygotes showed no significant effect.
• During reward anticipation, activation and EEG's contingent negative variation (CNV) decreased with increasing CFA.

Conclusions:

• Convergent genetic and environmental effects on reward processing were identified in a prospective study.
• Childhood stress is associated with higher reward sensitivity and reduced processing efficiency in genetically at-risk individuals.
• These findings help define a system mediating early environmental and genetic risk factors for potential intervention.