title: PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry activity in adolescents.
abstract: 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.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. forbese@upmc.edu
authors.forename: Erika E
authors.initials: EE
authors.lastname: Forbes
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Dahl
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
authors.forename: Hader
authors.initials: H
authors.lastname: Mansour
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Sciarrillo
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Holm
authors.forename: Eric E
authors.initials: EE
authors.lastname: Rodriguez
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D056044:Actigraphy / Q000379:methods; D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology* / Q000523:psychology; D000483:Alleles; D002648:Child; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D012201:Reward; D012890:Sleep / Q000235:genetics
chemical_list: C421902:PER2 protein, human; D056950:Period Circadian Proteins