Phenotypic effects of a bipolar liability gene among individuals with major depressive disorder

Abstract

Variations in voltage-dependent calcium channel L-type, alpha 1C subunit (CACNA1C) gene have been associated with bipolar disorder in a recent meta-analysis of genome-wide association studies [Ferreira et al., 2008]. The impact of these variations on other psychiatric disorders has not been yet investigated. Caucasian non-Hispanic participants in the STAR*D study of treatment for depression for whom DNA was available (N = 1213) were genotyped at two single-nucleotide polymorphisms (SNPs) (rs10848635 and rs1006737) in the CACNA1C gene. We examined putative phenotypic indicators of bipolarity among patients with major depression and elements of longitudinal course suggestive of latent bipolarity. We also considered remission and depression severity following citalopram treatment. The rs10848635 risk allele was significantly associated with lower levels of baseline agitation (P = 0.03; beta = -0.09). The rs1006737 risk allele was significantly associated with lesser baseline depression severity (P = 0.04; beta = -0.4) and decreased likelihood of insomnia (P = 0.047; beta = -0.22). Both markers were associated with an increased risk of citalopram-emergent suicidality (rs10848635: OR = 1.29, P = 0.04; rs1006737: OR = 1.34, P = 0.02). In this exploratory analysis, treatment-emergent suicidality was associated with two risk alleles in a putative bipolar liability gene.

Quantitative genetic research on sleep: A review of normal sleep, sleep disturbances and associated emotional, behavioural, and health-related difficulties

“…(99) Furthermore, the risk allele of the CACNA1C gene, which has previously been associated with bipolar disorder, has been found to be associated with reduced risk for insomnia symptoms in individuals with major depression. (100) Such studies highlight the importance of considering phenotypic covariation to maximise the likelihood of identifying molecular genetic variants associated with sleep disturbances.…”

Associação entre polimorfismos genéticos e transtorno bipolar

“…The polymorphism rs1006737 was also correlated with reduced severity of depression and insomnia. However, both alleles were associated with an increased risk of suicide during treatment for depression 18 . This is a clear demonstration that there is an overlap between genes in the biological basis of susceptibility to mental illness across the clinical spectrum 19 .…”

“…An analysis of these articles associated identified five genes as the most cited in the literature: CANAC1C [16][17][18][19][20][21][22][23][24] , DAOA [25][26][27][28][29][30][31][32] 22 . Some articles related the genetic polymorphism specifying the classification of TBI 8,25,27,32,35,36,39,41 , in addition to TBI and II 37 .…”

“…Some articles related the genetic polymorphism specifying the classification of TBI 8,25,27,32,35,36,39,41 , in addition to TBI and II 37 . The population studied by the authors of the articles are mostly from ocidente 18,20,22,26,28,30,32,[34][35][36][37][38] and a lower part are the oriente 25,27,33,43 .…”

CACNA1C rs1006737 genotype and bipolar disorder: Focus on intermediate phenotypes and cardiovascular comorbidity

“…Collectively, these studies provide the strongest evidence to date for a specific polymorphism associated with BD. Nonetheless, given the modest magnitude (odds ratio approximately 1.2) of the association between rs1006737 and BD, and given similar findings in recurrent Major Depressive Disorder and schizophrenia (SCZ) (Athanasiu et al, 2010;Casamassima et al, 2010b;Gonzalez et al, 2013;Green et al, 2010Green et al, , 2012Nyegaard et al, 2010;Williams et al, 2011), rs1006737 is likely associated with symptom clusters and/or intermediate phenotypes that are salient to BD rather than with BD as a monolithic construct. rs1006737 has been positively associated both with high depression scores among BD patients as well as with psychotic BD specifically (Lett et al, 2011).…”