PER2 rs2304672 Polymorphism Moderates Circadian-Relevant Reward Circuitry Activity in Adolescents

Forbes, Erika E.; Dahl, Ronald E.; Almeida, Jorge R.C.; Ferrell, Robert E.; Nimgaonkar, Vishwajit L.; Mansour, Hader; Sciarrillo, Samantha R.; Holm, Stephanie M.; Rodriguez, Eric E.; Phillips, Mary L.

doi:10.1016/j.biopsych.2011.10.012

« Previous Next »Biological Psychiatry
Volume 71, Issue 5 , Pages 451-457, 1 March 2012

PER2 rs2304672 Polymorphism Moderates Circadian-Relevant Reward Circuitry Activity in Adolescents

Erika E. Forbes
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Address correspondence to Erika E. Forbes, Ph.D., Western Psychiatric Institute and Clinic—Loeffler 319, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213
Ronald E. Dahl
- Community Health & Human Development and Joint Medical Program, University of California—Berkeley, Berkeley, California
Jorge R.C. Almeida
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Robert E. Ferrell
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania
Vishwajit L. Nimgaonkar
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Hader Mansour
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Samantha R. Sciarrillo
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Stephanie M. Holm
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Eric E. Rodriguez
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
Mary L. Phillips
- Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Psychological Medicine, Cardiff University, Cardiff, United Kingdom

Received 5 May 2011; received in revised form 5 October 2011; accepted 5 October 2011. published online 05 December 2011.

Background

Reward behavior in animals is influenced by circadian genes, including clock-pathway genes such as Period2 (PER2). Several forms of psychiatric illness are associated with both altered reward function and disturbances in circadian function. The PER2 single nucleotide polymorphism (SNP) rs2304672 has been associated with psychiatric illnesses involving reward dysfunction. Associations among circadian genes, function in neural reward circuits, and circadian-influenced behavior have not yet been studied in humans, however.

Methods

90 healthy adolescents underwent functional magnetic resonance imaging during a guessing task with monetary reward, genotyping for two PER2 SNPs (rs2304672, rs2304674), and actigraphy to measure sleep in their home environments. Weekend sleep midpoint, a behavioral index of circadian function, was derived from actigraphy. Puberty was measured by physical exam.

Results

The rs2304672 SNP predicted blood oxygenation level-dependent response to monetary reward as constrained by sleep midpoint. Later sleep midpoint was associated with reduced activity in a key component of reward circuitry, medial prefrontal cortex (mPFC; Brodmann area 9/10/32), to reward outcome (p_corrected < .05). G allele carriers showed reduced activity in mPFC relative to CC homozygotes.

Conclusions

Our findings are the first to indicate that circadian genes have a significant impact upon circadian-relevant reward circuitry in humans. These findings have the potential to elucidate gene-brain-behavior relationships underlying reward processing and psychopathology.

Key Words: Brain function , circadian function , clock-pathway genes , development , reward , PER2