Influence of DARPP-32 genetic variation on BOLD activation to happy faces

Soc Cogn Affect Neurosci. 2017 Oct 1;12(10):1658-1667. doi: 10.1093/scan/nsx089.

Abstract

Dopaminergic pathways play a crucial role in reward processing, and advanced age can modulate its efficiency. DARPP-32 controls dopaminergic function and is a chemical nexus of reward processing. In 61 younger (20-30 years) and older adults (54% ♀) (65-74 years), we examined how blood-oxygen-level dependent (BOLD) activation to emotional faces, vary over genotypes at three single nucleotide polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also assessed age-magnification of DARPP-32 effects on BOLD activation. We found that major homozygote G, T or A genotypes, with higher cortical expression of DARPP-32, higher dopamine receptor efficacy, and greater bias toward positive cues, had increased functional connectivity in cortical-subcortical circuits in response to happy faces, engaging the dorsal prefrontal cortex (DLPFC), fusiform gyrus (FG) and the midbrain (MB). Local BOLD response to happy faces in FG, and MB was age-dependent, so that older carriers of the major G, T or A alleles showed lesser activation than minor genotypes. These genetic variants of DARPP-32 did not modulate BOLD response to angry faces, or engagement of the inferior occipital gyrus, to happy or angry faces. Taken together our results lend support for a potential role of DARPP-32 genetic variants in neural response to potential reward triggering cues.

Keywords: DARPP-32; PPP1R1B; SNP; dopamine; happy faces; reward.

MeSH terms

  • Adult
  • Aged
  • Aging / psychology
  • Anger
  • Brain Mapping
  • Cerebral Cortex / metabolism
  • Cues
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / genetics*
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
  • Face*
  • Female
  • Functional Laterality / physiology
  • Genetic Variation
  • Genotype
  • Happiness*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Neural Pathways / physiology
  • Oxygen / blood
  • Photic Stimulation
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • PPP1R1B protein, human
  • Oxygen