No association of clock gene T3111C polymorphism and affective disorders

Bailer, Ursula F.; Wiesegger, G.; Leisch, Friedrich; Fuchs, Karoline; Leitner, Irene; Letmaier, Martin; Konstantinidis, Anastasios; Stastny, J.; Sieghart, Werner; Hornik, Kurt; Mitterauer, Bernhard; Kasper, Siegfried; Aschauer, Harald

doi:10.1016/j.euroneuro.2004.05.004

Cited by 45 publications

(27 citation statements)

References 21 publications

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“…Far less is known regarding the involvement of circadian genes in the vulnerability to MDD. No evidence of association was found between a CLOCK gene variation in MDD (Bailer et al, 2005;Desan et al, 2000;Kishi et al, 2009a), although a positive association with fluvoxamine response was reported in Japanese MDD patients (Kishi et al, 2009b).…”

Section: Introductionmentioning

confidence: 82%

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Soria

Martínez‐Amorós

Escaramís

et al. 2010

Neuropsychopharmacol

315

203

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Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3 0 near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p ¼ 0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity.

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Section: Introductionmentioning

confidence: 82%

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Soria

Martínez‐Amorós

Escaramís

et al. 2010

Neuropsychopharmacol

315

203

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“…The homozygous for this allele 3111C present several differences from the 3111T allele homozygous or heterozygous, in particular, show a doubling of the rate of recurrence of bipolar episodes and an increased recurrence of insomnia , Serretti, Cusin et al 2005. In contrast, other studies have not confirmed the role of this polymorphism in these circadian phenotypes nor have found any association with mood disorders (Bailer, Wiesegger et al 2005, Kishi, Kitajima et al 2009, Calati, Gaspar-Barba et al 2010, Choub, Mancuso et al 2011.…”

Section: Clock Genesmentioning

confidence: 90%

The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles

Abreu

Bragança²

2015

Journal of Affective Disorders

120

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“…In addition, Serretti and colleagues reported an association between T3111C and improved insomnia from fluvoxamine or paroxetine treatment (Serretti et al 2005). However, three genetic studies, including our previous study, reported no association between CLOCK and MDD (Bailer et al 2005;Desan et al 2000;Kishi et al 2008a). Thus, there is disagreement in the results of these studies as to treatment response and the pathophysiology of MDD (Gratacos et al 2008).…”

Section: Introductionmentioning

confidence: 88%

CLOCK may Predict the Response to Fluvoxamine Treatment in Japanese Major Depressive Disorder Patients

et al. 2009

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Recent studies have shown that selective serotonin reuptake inhibitors (SSRIs) have circadian properties, suggesting that the antidepressive action of SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of fluvoxamine treatment in 121 patients with Japanese major depressive disorder (MDD). The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remission as a SIGH-D score of less than seven at 8 weeks. We selected three tagging SNPs in CLOCK for the subsequent statistical association analysis. We detected a significant association between rs3736544, a synonymous polymorphism in exon 20, and the fluvoxamine therapeutic response in MDD in the allele/genotype-wise analyses. In addition, remission with fluvoxamine was also significantly associated with rs3736544. These associations remained significant after Bonferroni correction. Moreover, haplotype analysis findings supported these significant associations, which appeared to be due mainly to rs3736544, in the fluvoxamine therapeutic remission. Our results indicate that CLOCK genotype may be a predictor of fluvoxamine treatment response in Japanese MDD. However, our sample size was small, and a replication study using larger samples may be required for conclusive results.

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No association of clock gene T3111C polymorphism and affective disorders

Cited by 45 publications

References 21 publications

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

The bipolarity of light and dark: A review on Bipolar Disorder and circadian cycles

CLOCK may Predict the Response to Fluvoxamine Treatment in Japanese Major Depressive Disorder Patients

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