Turner Institute for Brain and Mental Health, Monash University, 18 Innovation Walk, Clayton, VIC 3800, Australia.
Turner Institute for Brain and Mental Health, Monash University, 18 Innovation Walk, Clayton, VIC 3800, Australia.
Drug Alcohol Depend. 2022 Jan 1;230:109183. doi: 10.1016/j.drugalcdep.2021.109183. Epub 2021 Nov 21.
Methamphetamine dependence is associated with social cognition deficits that may underpin negative social outcomes. However, there are considerable inter-individual differences in social cognition within people with methamphetamine dependence, with age of onset of methamphetamine use being a potential contributing factor.
We conducted two sequential studies examining the link between age of onset of methamphetamine use (adolescence versus young adulthood) and performance in social cognition tests: (1) a human cross-sectional study in 95 participants with methamphetamine dependence varying in age of onset (38 with adolescent onset and 57 with adult onset) and 49 drug-naïve controls; (2) a mice study in which we tested the effects of methamphetamine exposure during adolescence versus young adulthood on social interaction and aggression, and their potential neurochemical substrates in the striatal dopaminergic system.
We initially showed that people with methamphetamine dependence who started use in adolescence had higher antisocial beliefs (p = 0.046, Cohen's d=0.42) and worse emotion recognition (p = 0.031, Cohen's d=0.44) than those who started use during adulthood. We reasoned that this could be due to either social cognition deficits leading to earlier onset of methamphetamine use, or methamphetamine-induced neuroadaptive effects specific to adolescence. Mice experiments showed that methamphetamine exposure during adolescence specifically decreased social investigation during social interaction and upregulated striatal tyrosine hydroxylase (p < 0.05, Bonferroni corrected). There was no evidence of adolescent-specific methamphetamine effects on aggression or other measures of dopaminergic function.
Together, translational findings demonstrate heightened sensitivity to methamphetamine effects on social cognition during adolescence.
甲基苯丙胺依赖与社会认知缺陷有关，而这些缺陷可能是导致负面社会后果的原因。然而，在甲基苯丙胺依赖患者中，社会认知存在相当大的个体差异，甲基苯丙胺使用的发病年龄是一个潜在的影响因素。
我们进行了两项连续的研究，以考察甲基苯丙胺使用发病年龄（青春期与成年早期）与社会认知测试表现之间的关系：（1）一项横断面研究，共纳入 95 名甲基苯丙胺依赖患者（38 名发病年龄为青春期，57 名发病年龄为成年早期）和 49 名药物-naïve 对照者；（2）一项在小鼠中进行的研究，我们测试了青春期和成年早期暴露于甲基苯丙胺对社会互动和攻击性的影响，以及它们在纹状体多巴胺能系统中的潜在神经化学基础。
我们最初表明，青春期发病的甲基苯丙胺依赖患者具有更高的反社会信念（p=0.046，Cohen's d=0.42）和更差的情绪识别能力（p=0.031，Cohen's d=0.44）。我们推断，这可能是由于社会认知缺陷导致更早发病，或者是甲基苯丙胺引起的特定于青春期的神经适应性效应。小鼠实验表明，青春期暴露于甲基苯丙胺会特异性地减少社会互动中的社会调查，并上调纹状体酪氨酸羟化酶（p<0.05，Bonferroni 校正）。没有证据表明青春期特有的甲基苯丙胺对攻击性或其他多巴胺能功能测量有影响。
转化研究结果表明，青少年对甲基苯丙胺对社会认知的影响更为敏感。
