Abstract:

Ca(2+)-dependent activator protein for secretion 2 (CADPS2), a secretory granule
associate protein, mediates monoamine transmission and neurotrophin release. Both monoamines and neurotrophins play a crucial role in cognition, learning and memory. An aberrant splice variant of CADPS2, CADPS2ΔExon3, was reported to be associated with autism. Therefore, we examined the possible association between the expression of CADPS2/CADPS2ΔExon3 in peripheral blood and brain functions such as intelligence and memory. Quantitative polymerase chain reaction analysis was performed in 271 healthy adults (age range 20-74 years, mean ± SD 43.3 ± 15.3). Data on intelligence quotient (IQ) and memory were obtained by using full versions of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Wechsler Memory Scale-Revised (WMS-R), respectively. CADPS2 expression levels were not significantly associated with any scores/sub-scores of these scales. However, CADPS2ΔExon3 expression was significantly associated with lower IQ (p=0.022; effect size: η(p)(2)=0.031), particularly verbal IQ of WAIS-R (p=0.019; η(p)(2)=0.032), lower verbal memory (p=0.026; η(p)(2)=0.026) and delayed recall (p=0.042; η(p)(2)=0.021) of WMS-R. Our results suggest that CADPS2ΔExon3 affects intelligence and memory in the non-clinical population.

日本語要旨:

CADPS2はBDNFやモノアミンの放出に関わる分子で、その変異体CADPS2?Exon3は自閉症の血液に発現していることが報告されている。我々は前回の研究にて、統合失調症の死後脳でCADPS2やCADPS2?Exon3の発現が増えていることを見出したが、今回は健常者の脳機能とそれらの分子の血中の発現との関係を調べた。その結果、健常成人にも一定数のCADPS2?Exon3陽性者がおり、陽性者は院生者に比べIQや記憶力が低いことが判明した。このようにCADPS2?Exon3が成人の知的機能にも関わることが示唆され、その測定が発達障害や知的機能のマーカーとして使用できる可能性が見出された。