Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Center for Health Sciences, SRI International, Menlo Park, CA, USA.
Addict Biol. 2021 Mar;26(2):e12914. doi: 10.1111/adb.12914. Epub 2020 May 19.
Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.
外源性因素,如饮酒,和内源性因素,如气质和性别,可以调节青少年神经功能成熟的发展轨迹。我们研究了这些因素如何影响青少年饮酒低于酒精使用障碍(AUD)诊断阈值的大脑功能网络的性别二态性。基于来自国家青少年酒精和神经发育联盟(NCANDA)队列的 526 名青少年(基线时 12-21 岁)的 3 年、每年采集的纵向静息态功能磁共振成像(MRI)数据,我们分析了 23 个内在功能网络(IFN)的发展轨迹,用于:(1)在整个研究期间没有到低饮酒量的 259 名参与者中的性别二态性;(2)在两个年龄和性别匹配的 NCANDA 亚组(每组 76 名)中,一半是没有到低饮酒量,一半是中度到重度饮酒者的性别-酒精相互作用;(3)在所有 NCANDA 参与者中,性别特异性酒精剂量效应和多因素冲动性测量对 IFN 连接的调节作用。结果表明,在没有到低饮酒者中,性别差异随年龄的增长在枕下网络中减小,但在另外六个网络中,女孩的网络内连接强度比男孩弱。青少年饮酒的影响在女性中比男性更为明显,在三个 IFN 中。特别是,随着饮酒量的增加,女孩在两个运动网络中表现出更强的网络内连接性,而这些效应仅在女孩中被感觉寻求所介导。我们的结果表明,饮酒可能会通过更严重地破坏女孩网络效率的成熟来减弱自然减少的性别差异。性别-酒精-剂量效应可能解释了为什么女性比男性更容易受到与酒精相关的健康和心理社会后果的影响。