Neuroscience of Addiction (NofA) Lab, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
The Amsterdam Brain and Cognition Center (ABC), University of Amsterdam, Amsterdam, The Netherlands.
Addict Biol. 2021 Sep;26(5):e13003. doi: 10.1111/adb.13003. Epub 2021 Jan 28.
Although two thirds of patients with a cocaine use disorder (CUD) are female, little is known about sex differences in the (neuro)pathology of CUD. The aim of this explorative study was to investigate sex-dependent differences in prefrontal cortex (PFC) functioning during a working memory (WM) functional magnetic resonance imaging (fMRI) task in regular cocaine users (CUs), as PFC deficits are implicated in the shift from recreational cocaine use to CUD. Neural activation was measured using fMRI during a standard WM task (n-back task) in 27 male and 28 female CUs and in 26 male and 28 female non-cocaine users (non-CUs). Although there were no main or interaction effects of sex and group on n-back task performance, WM-related (2-back > 0-back) PFC functioning was significantly moderated by sex and group: female compared with male CUs displayed higher WM-related activation of the middle frontal gyrus (MFG), whereas female compared with male non-CUs displayed lower WM-related MFG activation. Additionally, WM-related activation of the inferior frontal gyrus, insula, and putamen was negatively associated with cocaine use severity in female but not male CUs. These data support the hypothesis of sex-dependent PFC differences in CUs and speculatively suggest that PFC deficits may be more strongly implicated in the development, continuation, and possibly treatment of CUD in females. Most importantly, the current data stress the importance of studying both males and females in psychiatry research as not doing so could greatly bias our knowledge of CUD and other psychiatric disorders.
尽管三分之二的可卡因使用障碍（CUD）患者为女性，但对于 CUD 的（神经）病理学中性别差异知之甚少。本探索性研究的目的是调查在可卡因使用者（CUs）的工作记忆（WM）功能磁共振成像（fMRI）任务中，前额叶皮层（PFC）功能的性别依赖性差异，因为 PFC 缺陷与从娱乐性可卡因使用转变为 CUD 有关。在标准 WM 任务（n-back 任务）期间，使用 fMRI 测量了 27 名男性和 28 名女性 CUs 以及 26 名男性和 28 名女性非可卡因使用者（非 CUs）的神经激活。尽管性别和组对 n-back 任务表现没有主要或交互作用，但 WM 相关（2-back>0-back）PFC 功能受到性别和组的显著调节：与男性 CUs 相比，女性 CUs 的中额回（MFG）WM 相关激活更高，而与男性非 CUs 相比，女性非 CUs 的 MFG 激活较低。此外，WM 相关的额下回、岛叶和壳核的激活与女性 CUs 而不是男性 CUs 的可卡因使用严重程度呈负相关。这些数据支持 CUs 中 PFC 性别差异的假设，并推测 PFC 缺陷可能更强烈地参与女性 CUD 的发展、持续，甚至可能的治疗。最重要的是，目前的数据强调了在精神病学研究中同时研究男性和女性的重要性，因为不这样做可能会极大地影响我们对 CUD 和其他精神障碍的认识。
