Schote et al. 1 2
Glucocorticoid receptor gene variants and lower expression of NR3C1 are associated with cocaine use
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Andrea B.Schotea,*, Kristina Jägera, Sara L. Krollb, Matthias Vonmoosb, Lea M. Hulkab, Katrin H. Prellerb, Jobst Meyera, Edna Grünblattc,d, Boris B. Quednowb,d,* Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy, and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland c University Clinic for Child and Adolescent Psychiatry, University of Zurich, Switzerland d NeuroscienceCenter Zurich, University and ETH Zurich, Switzerland a b
Abbreviated title NR3C1 and cocaine use Manuscript category Original Article
Manuscript characteristics Number of words in the abstract: 250 Number of words in the main text: 4958 Number of figures/tables: 6 Supplemental Material: yes
*Corresponding authors Andrea B. Schote, PhD Department of Neurobehavioral Genetics Institute of Psychobiology University of Trier Johanniterufer 15 D-54290 Trier, Germany Phone: +49 651 201 3708 E-Mail:
[email protected] Boris B. Quednow, PhD Experimental and Clinical Pharmacopsychology Department of Psychiatry, Psychotherapy and Psychosomatics Psychiatric Hospital of the University of Zurich Lenggstrasse 31 – H1 34 CH-8032 Zurich, Switzerland Phone: +41 44 384 2777 E-Mail:
[email protected] 1
Schote et al. 46
Abstract
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Animal and cross-sectional human studies suggest that chronic cocaine use is associated with altered
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responsivity of the hypothalamic-pituitary-adrenal (HPA) axis to stress. Moreover, increased
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susceptibility to stress has been proposed as an important factor for development, maintenance, and
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relapse of cocaine addiction. As the glucocorticoid receptor gene (NR3C1) mediates genomic effects
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of the stress hormone cortisol, we investigated NR3C1 expression and the association of NR3C1
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genotypes with cocaine use, addiction and comorbid psychiatric symptoms in 126 chronic cocaine
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users and 98 stimulant-naïve healthy controls. A comprehensive psychiatric assessment was
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performed including severity of depressive symptoms and current psychological distress. Whole
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blood NR3C1 mRNA levels were determined and six NR3C1 polymorphisms (rs10482605, rs41423247,
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rs10052957, rs6189, rs56149945, rs6198) were genotyped. Compared to controls, cocaine users
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showed significantly lower NR3C1 expression (p
