title: 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.
authors.affiliation: Division of Psychiatry, University of Pisa, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Casamassima
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Gary S
authors.initials: GS
authors.lastname: Sachs
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Smoller
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Cassano
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lattanzi
authors.forename: Jes
authors.initials: J
authors.lastname: Fagerness
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Stange
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis
mesh_terms: D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type