Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders
Open accessAbstract
BACKGROUND: Clinical and genetic studies suggest circadian clock genes may contribute to biological mechanisms underlying alcohol use disorders (AUD). In particular, the Per2 gene regulates alcohol consumption in mutant animals, and in humans with AUD, the 10870 variant in PER2 has been associated with alcohol consumption. However, with respect to function, the molecular clock remains largely uncharacterized in AUD patients. METHODS: In skin fibroblast cultures from well-characterized human AUD patients (n = 19) and controls (n = 13), we used a bioluminescent reporter gene (Per2::luc) to measure circadian rhythms in gene expression at high sampling density for 5 days. Cells were genotyped for the PER2 10870 variant. The rhythm parameters period and amplitude were then analyzed using a case-control design and by genetic and clinical characteristics of the AUD subjects. RESULTS: There were no differences between AUD cases and controls in rhythm parameters. However, period was inversely correlated with illness severity (defined as the number of alcohol dependence criteria met). The PER2 variant 10870 was not associated with differences in rhythm parameters. CONCLUSIONS: Our data suggest that differences in the cellular circadian clock are not pronounced in fibroblasts from AUD cases and controls. However, we found evidence that the circadian clock may be associated with an altered trajectory of AUD, possibly related to illness severity. Future work will be required to determine the mechanistic basis of this association.
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In 19 alcohol-dependent adults, Per2 rhythm amplitude and period were similar to those of a control group of 10 age- and race-matched adults, but within the alcohol-dependent group, the period of Per2 rhythms correlated with the number of AUD symptoms.
“Another study used bioluminescence methods to examine the rhythmicity of circadian gene expression (Per2) in skin fibroblasts collected from 19 alcohol-dependent adults (McCarthy, Fernandes, Kranzler, Covault, & Welsh, 2013). Rhythm amplitude and period in the alcohol-dependent group were similar to those of a control group of 10 age- and race-matched adults. Within the alcohol-dependent group, t”
From Sleep and circadian contributions to adolescent alcohol use disorder (2015) · cites this paper as McCarthy et al., 2013
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- Authors
- McCarthy, M. J., Fernandes, M., Kranzler, H. R., Covault, J. M., & Welsh, D. K.
- Affiliations
- University of California San Diego (US)
- Veterans Health Administration (US)
- University of Connecticut (US)
- Corresponding author
- McCarthy, Michael J.
- Venue
- Alcoholism Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2013-03-29
- Volume
- 37
- Issue
- 8
- Pages
- 1304-1310
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC3706548
- OpenAlex
- W2113534613
- Cited by
- 32
- References
- 40
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 4 · 2016: 3 · 2015: 3 · 2014: 4
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 BX001275, I01 BX001146)
- National Institute on Alcohol Abuse and Alcoholism (P60AA003510, R01AA021164, R21AA017584)
- National Institute of Mental Health (R01MH082945)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- circadian clock, alcoholism, circadian period, disease severity, dermal fibroblasts, circadian gene expression, bioluminescence reporter
- MeSH terms
- Ethanol, Cell Line, Circadian Rhythm, Female, Fibroblasts, Genotype, Humans, Male, Severity of Illness Index, Case-Control Studies, Alcohol-Related Disorders, Period Circadian Proteins, Circadian Clocks
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