The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males
The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males
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DOI：
10.1111/j.1399-5618.2011.00924.x
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Bitsios, Panos
中科院分区：
文献类型：
--
作者：
Roussos, Panos;Giakoumaki, Stella G.;Bitsios, Panos
目的：最近，rs 10994336 ANK 3和rs 1006737 CACNA 1C遗传变异被确定为双相情感障碍最一致的全基因组重要危险因素，而CACNA 1C变异也与精神分裂症和重度抑郁症有关。本研究的目的是研究的风险CACNA 1C和ANK 3等位基因的表型后果在一个大的同质队列的健康的年轻男性。方法：我们招募了703随机选择的，健康的军队应征入伍者（平均年龄22.1 +/- 3.0岁）从第一波的学习遗传学的精神分裂症项目在赫拉克利翁，克里特岛。在招募的受试者中，有530名受试者进入并完成了研究。受试者进行了评估前脉冲抑制（PPI），惊吓反应，神经心理学，和personality.Results：UNPHASED分析显示，rs 1006737 A等位基因与较低的外向性和较高的伤害回避，特质焦虑，偏执，而rs 10994336 T等位基因与较低的新奇寻求和行为激活分数（p < 0.01）。两个等位基因均与高惊吓反应性相关（p < 0.05）。有没有显着的关联与任何认知任务的性能或PPI.Conclusions：CACNA 1C基因型与焦虑和消极情绪的倾向，而ANK 3基因型与快感缺乏的倾向。这两种风险基因型都与高惊吓反应性相关，表明这些多态性在威胁/应激信号处理中的作用，可能在海马和/或杏仁核中。在这组健康男性中，在一系列广泛的执行功能测试中，没有一种风险基因型影响感觉运动门控或行为表现。
Objectives: The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression. The aim of this study was to examine the phenotypic consequences of the risk CACNA1C and ANK3 alleles in a large homogeneous cohort of healthy young males.Methods: We recruited 703 randomly selected, healthy army conscripts (mean age 22.1 +/- 3.0 years) from the first wave of the Learning on Genetics of Schizophrenia project in Heraklion, Crete. Of those recruited, 530 subjects entered and completed the study. Subjects were assessed for prepulse inhibition (PPI), startle reactivity, neuropsychology, and personality.Results: UNPHASED analysis revealed that the rs1006737 A-allele was associated with lower extraversion and higher harm avoidance, trait anxiety, and paranoid ideation, while the rs10994336 T-allele was associated with lower novelty seeking and behavioral activation scores (p < 0.01). Both alleles were associated with high startle reactivity (p < 0.05). There were no significant associations with any cognitive task performance or PPI.Conclusions: The CACNA1C genotype was associated with proneness to anxiety and negative mood, while the ANK3 genotype was associated with proneness to anhedonia. Both risk genotypes were associated with high startle reactivity, suggesting a role of these polymorphisms in threat/stress signal processing, probably in the hippocampus and/or amygdala. None of the risk genotypes affected sensorimotor gating or behavioral performance in an extensive battery of executive function tests in this cohort of healthy males.