CACNA1C risk variant affects reward responsiveness in healthy individuals

Transl Psychiatry. 2014 Oct 7;4(10):e461. doi: 10.1038/tp.2014.100.


The variant at rs1006737 in the L-type voltage-gated calcium channel (alpha 1c subunit) CACNA1C gene is reliably associated with both bipolar disorder and schizophrenia. We investigated whether this risk variant affects reward responsiveness because reward processing is one of the central cognitive-motivational domains implicated in both disorders. In a sample of 164 young, healthy individuals, we show a dose-dependent response, where the rs1006737 risk genotype was associated with blunted reward responsiveness, whereas discriminability did not significantly differ between genotype groups. This finding suggests that the CACNA1C risk locus may have a role in neural pathways that facilitate value representation for rewarding stimuli. Impaired reward processing may be a transdiagnostic phenotype of variation in CACNA1C that could contribute to anhedonia and other clinical features common to both affective and psychotic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / physiology*
  • Brain Mapping / methods
  • Calcium Channels, L-Type / genetics*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Reference Values
  • Reward*
  • Risk
  • Young Adult


  • CACNA1C protein, human
  • Calcium Channels, L-Type