Hernandez Leanna M, Kim Minsoo, Hernandez Cristian, Thompson Wesley, Fan Chun Chieh, Galván Adriana, Dapretto Mirella, Bookheimer Susan Y, Fuligni Andrew, Gandal Michael J
Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Program in Neurobehavioral Genetics, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Biol Psychiatry Glob Open Sci. 2022 Jan 17;3(1):139-148. doi: 10.1016/j.bpsgos.2021.12.011. eCollection 2023 Jan.
Childhood sleep problems are common and among the most frequent and impairing comorbidities of childhood psychiatric disorders. In adults, sleep disturbances are heritable and show strong genetic associations with brain morphology; however, little is known about the genetic architecture of childhood sleep and potential etiological links between sleep, brain development, and pediatric-onset psychiatric symptoms.
Using data from the Adolescent Brain Cognitive Development Study ( = 4428 for discovery/replication, = 4728; age 9-10 years), we assessed phenotypic relationships, heritability, and genetic correlations between childhood sleep disturbances (insomnia, arousal, breathing, somnolence, hyperhidrosis, sleep-wake transitions), brain size (surface area, cortical thickness, volume), and dimensional psychopathology.
Sleep disturbances showed widespread positive associations with multiple domains of childhood psychopathology; however, only insomnia showed replicable associations with smaller brain surface area. Among the sleep disturbances assessed, only insomnia showed significant heritability ( = 0.15, .05) and showed substantial genetic correlations with externalizing and attention-deficit/hyperactivity disorder symptomatology ( s > 0.80, s < .05). We found no evidence of genetic correlation between childhood insomnia and brain size. Furthermore, polygenic risk scores calculated from genome-wide association studies of adult insomnia and adult brain size did not predict childhood insomnia; instead, polygenic risk scores trained using attention-deficit/hyperactivity disorder genome-wide association studies predicted decreased surface area at baseline as well as insomnia and externalizing symptoms longitudinally.
Findings demonstrate a distinct genetic architecture underlying childhood insomnia and brain size and suggest genetic overlap between childhood insomnia and attention-deficit/hyperactivity disorder symptomatology. Additional research is needed to examine how genetic risk manifests in altered developmental trajectories and comorbid sleep/psychiatric symptoms across adolescence.
儿童睡眠问题很常见,是儿童精神疾病中最常见且具有损害性的共病之一。在成年人中,睡眠障碍具有遗传性,并且与脑形态显示出很强的基因关联;然而,关于儿童睡眠的遗传结构以及睡眠、脑发育和儿童期精神症状之间潜在的病因联系,我们所知甚少。
利用青少年大脑认知发展研究的数据(发现/重复分析时n = 4428,n = 4728;年龄9 - 10岁),我们评估了儿童睡眠障碍(失眠、觉醒、呼吸、嗜睡、多汗、睡眠 - 觉醒转换)、脑容量(表面积、皮质厚度、体积)和维度精神病理学之间的表型关系、遗传度和基因相关性。
睡眠障碍与儿童精神病理学的多个领域呈现广泛的正相关;然而,只有失眠与较小的脑表面积呈现可重复的关联。在所评估的睡眠障碍中,只有失眠显示出显著的遗传度(h² = 0.15,p <.05),并且与外化症状和注意力缺陷/多动障碍症状表现出实质性的基因相关性(rs > 0.80,ps <.05)。我们没有发现儿童失眠与脑容量之间存在基因相关性的证据。此外,从成人失眠和成人脑容量的全基因组关联研究中计算出的多基因风险评分并不能预测儿童失眠;相反,使用注意力缺陷/多动障碍全基因组关联研究训练的多基因风险评分在纵向预测了基线时脑表面积的减少以及失眠和外化症状。
研究结果表明儿童失眠和脑容量存在独特的遗传结构,并提示儿童失眠与注意力缺陷/多动障碍症状表现之间存在基因重叠。需要进一步的研究来探讨遗传风险如何在整个青春期改变的发育轨迹以及共病的睡眠/精神症状中表现出来。