Effects of the Circadian Rhythm Gene Period 1 (<i>Per1</i>) on Psychosocial Stress-Induced Alcohol Drinking

Li, Dong; Bilbao, Ainhoa; Laucht, Manfred; Henriksson, Richard; Yakovleva, Tatjana; Ridinger, Monika; Desrivières, Sylvane; Clarke, Toni‐Kim; Lourdusamy, Anbarasu; Smolka, Michael N.; Cichon, Sven; Blomeyer, Dorothea; Treutlein, Jens; Perreau-Lenz, Stéphanie; Witt, Stephanie H.; Leonardi-Essmann, Fernando; Wodarz, Norbert; Zill, Peter; Soyka, Michael; Albrecht, Urs; Rietschel, Marcella; Lathrop, Mark; Bakalkin, Georgy; Spanagel, Rainer; Schumann, Gunter

doi:10.1176/appi.ajp.2011.10111579

Cited by 112 publications

(112 citation statements)

References 32 publications

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“…Deletion of clock genes causes pronounced cognitive and behavioural effects throughout the animal kingdom [41]. Period1-deficient mice display alterations in glucocorticoid rhythmicity [42], addiction [43], muscle strength [44], colonic motility [45], fertility [17,46] and memory [16].…”

Section: (B) Innate Routine Behaviour In Laboratory Micementioning

confidence: 99%

The clock genePeriod1regulates innate routine behaviour in mice

et al. 2014

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Laboratory mice are well capable of performing innate routine behaviour programmes necessary for courtship, nest-building and exploratory activities although housed for decades in animal facilities. We found that in mice inactivation of the clock gene Period1 profoundly changes innate routine behaviour programmes like those necessary for courtship, nest building, exploration and learning. These results in wild-type and Period1 mutant mice, together with earlier findings on courtship behaviour in wild-type and period-mutant Drosophila melanogaster, suggest a conserved role of Period-genes on innate routine behaviour. Additionally, both per-mutant flies and Period1-mutant mice display spatial learning and memory deficits. The profound influence of Period1 on routine behaviour programmes in mice, including female partner choice, may be independent of its function as a circadian clock gene, since Period1-deficient mice display normal circadian behaviour.

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Section: (B) Innate Routine Behaviour In Laboratory Micementioning

confidence: 99%

The clock genePeriod1regulates innate routine behaviour in mice

et al. 2014

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“…In mice, alcohol is more intoxicating at night than during the day, and genetic knockout of Per2 eliminates this differential sensitivity, leading to overall increases in alcohol intake across the 24 hr cycle [112]. Per1 mutants consume more alcohol than controls, but only following a social defeat stress [113], and Per3 has been associated with alcohol preference and stress response in mice [114]. Mice bred for high alcohol intake have shorter freerunning circadian periods [115].…”

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confidence: 99%

“…In human studies, variants in several clock genes have been associated with various alcohol-related phenotypes: BMAL1/2 (ARNTL1/2) variants are associated with alcohol dependence and alcohol intake [117]; PER1 with alcohol consumption in adolescents and adult alcoholics [113]; PER2 with high alcohol intake and interaction with insomnia and alcohol consumption in young males [35,118]; and CLOCK with co-morbid AUD and depressive disorders [119]. Using a bioluminescent Per2::luc reporter to measure gene expression rhythms in human fibroblasts, a relationship between AUD severity and rhythms was found, in which the more severely affected alcoholics had shorter circadian periods, consistent with the studies of alcohol-preferring mice [120].…”

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confidence: 99%

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf

McCarthy

Welsh

2014

Curr Psychiatry Rep

146

100

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Many psychiatric disorders are characterized by circadian rhythm abnormalities including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to, and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders including posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

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“…Using mouse models, researchers have found that circadian rhythmicity, which governs how an individual adapts to their internal and external environment, shapes the rewarding effects of alcohol use [53]. Several studies have found links between clock genes and alcohol dependence in humans [54,55] and in a sample of 268 young adults, the association between stressful life events and alcohol use was shown to be stronger among individuals who carried the AA genotype of the period circadian clock (PER) gene than among G allele carriers [56].…”

Section: Moderators Of Clock Genesmentioning

confidence: 99%

Gene-Environment Interplay and Substance Use: A Review of Recent Findings

2015

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Substance use problems are chronic and common public health problems. We review recent studies that implicate genetic and environmental factors in their etiology. Although findings are mixed with respect to specific genotypes, some patterns are evident. For example, exposure to peers or parents who engage in high rates of substance use tends to exacerbate genetic diatheses or eliminate the protective effects of certain genotypes. We discuss reasons for mixed findings and highlight the need for translational research to advance understanding of gene function as well as new methods for using genomewide data in biologically relevant pathways.

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Effects of the Circadian Rhythm Gene Period 1 (Per1) on Psychosocial Stress-Induced Alcohol Drinking

Cited by 112 publications

References 32 publications

The clock genePeriod1regulates innate routine behaviour in mice

The clock genePeriod1regulates innate routine behaviour in mice

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Gene-Environment Interplay and Substance Use: A Review of Recent Findings

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