PER2 rs2304672 polymorphism moderates circadian-relevant reward circuitry activity in adolescents
Open accessAbstract
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.
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Changes in sleep timing and chronotype are associated with altered reward-related brain function in adolescents.
“These changes in sleep timing and chronotype are associated with altered reward-related brain function in adolescents (80–82).”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [81]
Later sleep timing is associated with reduced medial prefrontal cortex and ventral striatum responses to monetary reward.
“Later sleep timing is also associated with reduced mPFC (81) and VS responses to monetary reward (85).”
From Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents (2018) · cites this paper as [81]
Later sleep timing was associated with reduced mPFC response to monetary reward in healthy 11-13-year-olds.
“The aforementioned fMRI study of healthy 11–13-year-olds (Forbes et al., 2012) reported that later sleep timing was associated with reduced mPFC response to monetary reward.”
From Sleep and circadian contributions to adolescent alcohol use disorder (2015) · cites this paper as Forbes et al., 2012
In adolescents ages 11 to 13, genotype for Per2 polymorphism rs2304672 is differentially related to activation of the medial prefrontal cortex in response to a monetary reward task.
“In the sole published study in adolescents (ages 11 to 13 years), Forbes and colleagues (Forbes et al., 2012) found that the genotype for a particular Per2 polymorphism (rs2304672) is differentially related to activation of the medial prefrontal cortex (mPFC) in response to a monetary reward task.”
From Sleep and circadian contributions to adolescent alcohol use disorder (2015) · cites this paper as Forbes et al., 2012
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Self-citation
- Authors
- Forbes, E. E., Dahl, R. E., Almeida, J. R. C., Ferrell, R. E., Nimgaonkar, V. L., Mansour, H., Sciarrillo, S. R., Holm, S. M., Rodriguez, E. E., & Phillips, M. L.
- Affiliations
- University of Pittsburgh (US)
- University of California, Berkeley (US)
- Corresponding author
- Forbes, Erika E.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 71
- Issue
- 5
- Pages
- 451-457
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3323120
- OpenAlex
- W1966088236
- Cited by
- 83
- References
- 40
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 4 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 8 · 2016: 4 · 2015: 10 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- National Institutes of Health (R01-DA018910, R01-DA026222)
- Forbes & D.S. Shaw (R01-MH076971, K01-MH074769)
- NIH (RC1-MH088913)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- Per2, circadian genes, clock genes, reward processing, monetary rewards, medial prefrontal cortex, sleep midpoint, adolescents, puberty, gene-brain-behavior relationship, actigraphy
- MeSH terms
- Adolescent, Adolescent Behavior, Alleles, Child, Circadian Rhythm, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Psychomotor Performance, Reward, Sleep, Prefrontal Cortex, Polymorphism, Single Nucleotide, Actigraphy, Period Circadian Proteins, Functional Neuroimaging
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