Calcium channel risk allele linked to executive function in bipolar disorder

Researchers have found an allele in a voltage-gated calcium gene that is associated with an increased risk for poor executive function in patients with bipolar disorder (BD).

They report that patients with BD carrying the Met/Met genotype of the single nucleotide polymorphism (SNP) rs1006737 in the a1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene had worse executive function than those carrying the Val/Val genotype.

This was "regardless of manic or depressive symptoms," they note. Also, "no effect of this allele on executive function was observed in healthy controls."

Marcio Gerhardt Coeiro-de-Souza (University of Sao Paulo, Brazil) and colleagues say: "The fact that the CACNA1C risk allele influenced executive function in BD, but not in control individuals reflects the specificity of calcium-signaling alterations to the cognitive function of BD."

They genotyped 109 BD I patients and 96 mentally healthy individuals for the CACNA1C SNP rs1006737. The genotype distribution was 11.4% for Met/Met, 39.0% for Val/Met, and 49.6% for Val/Val.

The participants then completed four tests of executive function: Wechsler Adult Intelligence Scale III (WAIS-III) Letter-Number Sequence subtest (WAIS-LNS), digit span (WAISDS), trial making test (TMT), and Wisconsin Card Sorting Test (WCST).

Patients with BD carrying the Met/Met genotype scored significantly worse on all four tests than their peers carrying the Val/Val genotype.

Multiple analysis of covariance, taking into account education, age, and severity of depressive and manic symptoms, showed that the Met/Met genotype had the greatest effect on WCST conceptual level responses, WCST error responses, WAIS block design, and TMT-A, explaining 6.3%, 6.6%, 6.8%, and 7.8% of variance in scores, respectively.

The researchers conclude: "We have described the effect of one of the most strongly associated risk genes for BD on executive function in this disorder.

"Considering the specificity of cognitive dysfunctions associated to the CACNA1C Met allele for BD, we believe that alterations in the calcium-signaling pathway should be a key focus of future studies on cognitive degeneration in BD."

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