The new risk variant CACNA1C and brain circuits in schizophrenia

Excerpt

In recent genome-wide association studies of severe psychiatric disorders, several risk genes have been detected, but their neurobiological function is widely unknown. A polymorphism in the gene encoding the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) has been associated with schizophrenia and bipolar disorder and may have impact on structure and function of the amygdala. Wolf et al. [1] investigated the influence of the SNP rs1006737 in CACNA1C on gray matter volumes of the amygdala in patients with schizophrenia, bipolar disorder and obsessive compulsive disorder (OCD). The risk genotype had significant effect on the relative amygdala volume in patients with schizophrenia, while this group and bipolar patients had a smaller left amygdala compared to controls. This supports the hypothesis of disturbed calcium metabolism as a neurobiological background of affective symptoms in schizophrenia. However, CACNA1C is also known to be involved in learning and memory. In a functional MRI study of two independent samples of healthy probands, Krug et al. [2] investigated the impact of rs1006737 on episodic memory encoding and retrieval in the right hippocampus. In both samples, they replicated that in the retrieval condition, carriers of the minor allele (A) had lower activations than G/G allele carriers, thus strengthening the hypothesis that this risk genotype is associated with dysfunction of hippocampus-related memory processes. …