CRY 2 Is Associated with Depression

Background: Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated. Principal Findings: We observed a marked diurnal variation in human CRY2 mRNA levels from peripheral blood mononuclear cells and a significant up-regulation (P = 0.020) following one-night total sleep deprivation, a known antidepressant. In depressed bipolar patients, levels of CRY2 mRNA were decreased (P = 0.029) and a complete lack of increase was observed following sleep deprivation. To investigate a possible genetic contribution, we undertook SNP genotyping of the CRY2 gene in two independent population-based samples from Sweden (118 cases and 1011 controls) and Finland (86 cases and 1096 controls). The CRY2 gene was significantly associated with winter depression in both samples (haplotype analysis in Swedish and Finnish samples: OR = 1.8, P = 0.0059 and OR = 1.8, P = 0.00044, respectively). Conclusions: We propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression. Citation: Lavebratt C, Sjöholm LK, Soronen P, Paunio T, Vawter MP, et al. (2010) CRY2 Is Associated with Depression. PLoS ONE 5(2): e9407. doi:10.1371/ journal.pone. 0009407 Editor: Andreas Reif, University of Wuerzburg, Germany Received September 25, 2009; Accepted February 1, 2010; Published February 24, 2010 Copyright: 2010 Lavebratt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported in part by grants from Academy of Finland (#201097 and #210262, www.aka.fi) and The Finnish Medical Foundation to Dr. Partonen, from Academy of Finland (#203425, www.suomenlaaketieteensaatio.fi) and Helsinki University Central Hospital (TYH538) to Dr. Paunio, from the Swedish Research Council (2005-6245, 2006-4670, www.vr.se), the Stockholm County Council (ALF, www.forskningsstod.sll.se) and Karolinska Institutet Foundations (www.ki.se) to Drs. Lavebratt and Schalling, by Public Health Service research grant M01 RR00827 from the National Center for Research Resource (www.ncrr.nih.gov) to UCI, Biomarker research grant MH 024370 to Dr. Vawter from the National Institute of Mental Health (www.nimh.nih.gov), and from the William Lion Penzner Foundation to Drs. Vawter and Bunney. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Dr. Vawter is a co-founder of a diagnostic testing company AbaStar MDx, Dr. Kelsoe is consultant for AstraZeneca, on speakers bureau for Merck, and founder, board member and hold equity in diagnostic testing company Psynomics, all in compliance with UCSD guidelines. Dr. Bunney is a member of the scientific advisory boards of NeoSync, Inc., CNS Response, Inc. and Thuris Corporation and consultant for NeuDezine. None of these commercial affiliations played any role in this study. * E-mail: catharina.lavebratt@ki.se