CRY2 Is Associated with Depression

Abstract

BackgroundAbnormalities 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 FindingsWe 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).ConclusionsWe propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression.

Clock genes in human alcohol abuse and comorbid conditions

“…In addition, currently, there are no published data from Cry2 mutant mice on tests that induce anxiety-like or depressive-like behaviors, or on their alcohol intake. As such, this finding supports the view that CRY2 is clearly a "mood gene", since it is associated with a range of depressive phenotypes, including winter depression, on the basis of major depressive disorder (Lavebratt, Sjöholm, Soronen, et al, 2010), bipolar disorder (Sjöholm, Backlund, et al, 2010), the depressive episode of bipolar disorder (Lavebratt, Sjöholm, Soronen, et al, 2010), a chronic course of depressive symptoms due to major depressive disorder or bipolar disorder (Fiedorowicz, Coryell, Akhter, & Ellingrod, 2012), and dysthymia that is chronic depression (Kovanen, Kaunisto, Donner, Saarikoski, & Partonen, 2013).…”

“…In a sample of 712 patients with bipolar disorder and 1044 controls, two risk haplotypes and one protective haplotype in CRY2 were identified for bipolar disorder with the feature of rapid cycling (Sjöholm, Backlund, et al, 2010). The study by Lavebratt, Sjöholm, Soronen, et al (2010) demonstrated that CRY2 mRNA expression, as assessed from peripheral blood mononuclear cells at several times during one-night sleep deprivation, was decreased in depressed patients with bipolar disorder, as compared with controls, and that total sleep deprivation did not induce any increase in CRY2 mRNA levels in the non-responsive patients opposite to the change seen in the controls.…”

“…Mansour et al (2009) found no association with bipolar disorder in their further analysis of 252 SNPs of 18 genes in 523 patients with bipolar type 1 disorder and 477 controls, but NPAS2 rs17025005 and CRY2 rs1554338 suggested nominal associations with bipolar type 1 disorder. Further, the hypothesis-driven study by Sjöholm, Backlund, et al (2010) tested whether the 4 SNPs of CRY2 that had been associated with winter depression using samples of 204 patients and 2107 controls from two independent population-based studies (Lavebratt, Sjöholm, Soronen, et al, 2010) are associated with bipolar disorder. In a sample of 712 patients with bipolar disorder and 1044 controls, two risk haplotypes and one protective haplotype in CRY2 were identified for bipolar disorder with the feature of rapid cycling (Sjöholm, Backlund, et al, 2010).…”

Effect of sleep deprivation on rhythms of clock gene expression and melatonin in humans

“…Except for the HSPA1B gene, which does not contain introns, primers were designed to span at least one exon-exon junction using Primer-BLAST (http://www.ncbi.nlm.nih.gov/tools/primer-blast/), or were taken from published literature (Archer et al, 2008;Kimura et al, 2011;Lavebratt et al, 2010;Visser et al, 2011;Wu et al, 2006), and were checked for transcript specificity using the UCSC In-silico PCR tool (http://genome.ucsc.edu/). Primer sequences are given in Supplementary Table S1.…”

Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics

“…Several genomic studies support the association between CLOCK genes and depression (Lavebratt et al 2010;Soria et al 2010;Wulff et al 2010;McCarthy et al 2012) and see Wulff et al (2010) for review. A gene-wide test by Soria et al (2010), utilising a large sample of patients with major depressive disorder (MDD) and 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes, found significant associations in CRY1 and NPAS2 SNPs in depressed patients versus controls.…”