Fortgang R G, Hultman C M, van Erp T G M, Cannon T D
Department of Psychology,Yale University,New Haven,CT,USA.
Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
Psychol Med. 2016 May;46(7):1497-507. doi: 10.1017/S0033291716000131. Epub 2016 Feb 22.
Impulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis.
We focused on five subfacets of impulsivity: self-reported attentional, motor, and non-planning impulsivity, self-reported sensation seeking, and a behavioral measure of motor inhibition (stop signal reaction time; SSRT). We examined these facets within and across disorder proband and co-twin groups, modeled heritability, and tested for endophenotypic patterning in a sample of twin pairs recruited from the Swedish Twin Registry (N = 420).
We found evidence of moderate to high levels of heritability for all five subfacets. All three proband groups and their unaffected co-twins showed elevations on attentional, motor, and non-planning impulsivity. Schizophrenia probands (but not their co-twins) showed significantly lower sensation seeking, and schizophrenia and bipolar disorder probands (but not in their co-twins) had significantly longer SSRTs, compared with healthy controls and the other groups.
Attentional, motor, and non-planning impulsivity emerged as potential shared endophenotypes for the three disorders, whereas sensation seeking and SSRT were associated with phenotypic affection but not genetic loading for these disorders.
冲动性作为躁狂发作期间及发作间期的一种临床特征与双相情感障碍相关,并且被认为是该疾病的一种潜在内表型。精神分裂症和重度抑郁症与双相情感障碍存在大量的遗传重叠,而且这两种疾病也与冲动性增加有关。然而,对于这些疾病在冲动性的不同子方面的重叠程度,以及任何重叠是纯粹表型的还是由于共享遗传素质,人们知之甚少。
我们聚焦于冲动性的五个子方面:自我报告的注意力、运动和非计划性冲动性,自我报告的感觉寻求,以及运动抑制的行为测量(停止信号反应时间;SSRT)。我们在疾病先证者组和同卵双胞胎组内及组间检查了这些方面,对遗传度进行建模,并在从瑞典双胞胎登记处招募的双胞胎样本(N = 420)中测试内表型模式。
我们发现所有五个子方面都有中度到高度遗传度的证据。所有三个先证者组及其未受影响的同卵双胞胎在注意力、运动和非计划性冲动性方面都有所升高。与健康对照组和其他组相比,精神分裂症先证者(而非其同卵双胞胎)的感觉寻求显著降低,精神分裂症和双相情感障碍先证者(而非其同卵双胞胎)的SSRT显著更长。
注意力、运动和非计划性冲动性成为这三种疾病潜在的共享内表型,而感觉寻求和SSRT与这些疾病的表型影响相关,但与遗传负荷无关。