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

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.
AuthorsFrancesco Casamassima, Jie Huang, Maurizio Fava, Gary S Sachs, Jordan W Smoller, Giovanni B Cassano, Lorenzo Lattanzi, Jes Fagerness, Jonathan P Stange, Roy H Perlis
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 153B Issue 1 Pg. 303-9 (Jan 5 2010) ISSN: 1552-485X [Electronic] United States
PMID19388002 (Publication Type: Journal Article, Multicenter Study)
Copyright(c) 2009 Wiley-Liss, Inc.
Chemical References
  • CACNA1C protein, human
  • Calcium Channels, L-Type
  • Alleles
  • Bipolar Disorder (genetics)
  • Calcium Channels, L-Type (genetics)
  • Depressive Disorder, Major (genetics)
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide

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