These modifications in brain architecture associated with CACNA1C might reflect a neurobiological marker predisposing to affective disorders and concomitant alterations in emotion perception.
Variations in expression of CACNA1C in the nucleus accumbens may mediate human risk for developing mood disorders and be a target for therapeutic intervention.
Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression.
Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders.
These results suggest that CACNA1C is involved in the genetic architecture of endophenotypes for affective disorders and schizophrenia, and that it shows a distinct sex-specific effect.
Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders.
We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders.
Our preclinical results support a role for CACNA1C in mood disorder pathophysiology, and the combination of human genetic and preclinical data support an interaction between sex and genotype.