Section of Neurobiology of Psychosis, Institute of Psychiatry, King's College London, London, United Kingdom.
PLoS One. 2011 Jan 31;6(1):e16671. doi: 10.1371/journal.pone.0016671.
Abnormalities in cognition have been reported in patients with Bipolar Disorder (BD) and their first degree relatives, suggesting that susceptibility genes for BD may impact on cognitive processes. Recent genome-wide genetic studies have reported a strong association with BD in a single nucleotide polymorphism (SNP) (rs10994336) within ANK3, which codes for Ankyrin 3. This protein is involved in facilitating the propagation of action potentials by regulating the assembly of sodium gated ion channels. Since ANK3 influences the efficiency of transmission of neuronal impulses, allelic variation in this gene may have widespread cognitive effects. Preclinical data suggest that this may principally apply to sequential signal detection, a core process of sustained attention.
METHODOLOGY/PRINCIPAL FINDINGS: One hundred and eighty-nine individuals of white British descent were genotyped for the ANK3 rs10994336 polymorphism and received diagnostic interviews and comprehensive neurocognitive assessment of their general intellectual ability, memory, decision making, response inhibition and sustained attention. Participants comprised euthymic BD patients (n = 47), their unaffected first-degree relatives (n = 75) and healthy controls (n = 67). The risk allele T was associated with reduced sensitivity in target detection (p = 0.0004) and increased errors of commission (p = 0.0018) during sustained attention regardless of diagnosis. We found no effect of the ANK3 genotype on general intellectual ability, memory, decision making and response inhibition.
CONCLUSIONS/SIGNIFICANCE: Our results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for BD. However, our results require independent replication and confirmation that ANK3 (rs10994336) is a direct functional variant.
双相情感障碍（BD）患者及其一级亲属的认知功能异常已被报道，这表明 BD 的易感基因可能影响认知过程。最近的全基因组遗传研究报告称，ANK3 内的单核苷酸多态性（SNP）（rs10994336）与 BD 强烈相关，ANK3 编码锚蛋白 3。该蛋白通过调节钠门控离子通道的组装来促进动作电位的传播。由于 ANK3 影响神经元冲动传递的效率，该基因的等位基因变异可能具有广泛的认知影响。临床前数据表明，这主要适用于顺序信号检测，这是持续注意力的核心过程。
方法/主要发现：189 名白种英国人种被 ANK3 rs10994336 多态性基因分型，并接受了诊断访谈和全面的神经认知评估，以评估他们的一般智力、记忆、决策、反应抑制和持续注意力。参与者包括情绪稳定的 BD 患者（n=47）、未受影响的一级亲属（n=75）和健康对照组（n=67）。风险等位基因 T 与持续注意力期间目标检测的敏感性降低（p=0.0004）和错误判断增加（p=0.0018）相关，无论诊断如何。我们没有发现 ANK3 基因型对一般智力、记忆、决策和反应抑制有影响。
结论/意义：我们的结果表明，ANK3 的等位基因变异影响与信号检测相关的认知过程，这种机制可能与 BD 的风险有关。然而，我们的结果需要独立复制和确认 ANK3（rs10994336）是否是直接的功能变体。
