Carli Giulia, Cavicchioli Marco, Martini Anna Lisa, Bruscoli Matteo, Manfredi Antonella, Presotto Luca, Mazzeo Christian, Sestini Stelvio, Perani Daniela
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Faculty of Psychology, Vita-Salute San Raffaele University, Milan, Italy.
Brain Connect. 2023 Sep;13(7):370-382. doi: 10.1089/brain.2022.0076. Epub 2023 May 29.
Attention-deficit hyperactivity disorder (ADHD) in adulthood shows high co-occurrence rates with cocaine use disorder (CoUD). The self-medication hypothesis (SMH) provides a theoretical explanation for this comorbidity. This study investigates the neurobiological mechanisms that could support SMH in adult patients with attention-deficit hyperactivity disorder with cocaine use disorder (ADHD-CoUD). We included 19 ADHDCoUD patients (84.2% male; age: 32.11 years [7.18]) and 16 CoUD patients (68.7% male; age: 36.63 years [8.12]). All subjects underwent a fluorine-18-fluorodeoxyglucose positron emission tomography (F-FDG PET) brain scan. We tested brain metabolism differences between ADHD-CoUD and CoUD patients using voxel-based and regions of interest (ROIs)-based analyses. The correlation between dependence/abstinence duration and regional brain metabolism was also assessed in the two groups. Lastly, we investigated the integrity of brain metabolic connectivity of mesocorticolimbic and nigrostriatal dopaminergic systems, and large-scale brain networks involved in ADHD and addictions. The voxel-wise and ROIs-based approaches showed that ADHD-CoUD patients had a lower metabolism in the thalamus and increased metabolism in the amygdala and parahippocampus, bilaterally, than CoUD subjects and healthy controls (HCs). Metabolism in the thalamus negatively correlated with years of dependence in ADHD-CoUD patients. Moreover, connectivity analyses revealed that ADHD-CoUD patients had a more preserved metabolic connectivity than CoUD patients in the dopaminergic networks and large-scale networks involved in self-regulation mechanisms of attention and behaviors (i.e., anterior default mode network [ADMN], executive network [ECN], and anterior salience network [aSAN]). We demonstrated distinct neuropathological substrates underlying substance-use behaviors in ADHD-CoUD and CoUD patients. Furthermore, we provided neurobiological evidence in support of SMH, demonstrating that ADHD-CoUD patients might experience short-term advantages of cocaine assumption (i.e., compensation of dopaminergic deficiency and related cognitive-behavioral deficits).
成人注意力缺陷多动障碍（ADHD）与可卡因使用障碍（CoUD）的共现率很高。自我用药假说（SMH）为这种共病现象提供了一种理论解释。本研究调查了患有可卡因使用障碍的成人注意力缺陷多动障碍患者（ADHD-CoUD）中支持自我用药假说的神经生物学机制。我们纳入了19名ADHD-CoUD患者（84.2%为男性；年龄：32.11岁[7.18]）和16名CoUD患者（68.7%为男性；年龄：36.63岁[8.12]）。所有受试者均接受了氟-18-氟脱氧葡萄糖正电子发射断层扫描（F-FDG PET）脑部扫描。我们使用基于体素和基于感兴趣区域（ROIs）的分析方法，测试了ADHD-CoUD患者和CoUD患者之间的脑代谢差异。还评估了两组中依赖/戒断持续时间与区域脑代谢之间的相关性。最后，我们研究了中脑边缘和黑质纹状体多巴胺能系统以及参与ADHD和成瘾的大规模脑网络的脑代谢连通性的完整性。基于体素和基于ROIs的方法显示，与CoUD受试者和健康对照（HCs）相比，ADHD-CoUD患者双侧丘脑代谢较低，杏仁核和海马旁回代谢增加。ADHD-CoUD患者丘脑中的代谢与依赖年限呈负相关。此外，连通性分析显示，在涉及注意力和行为自我调节机制的多巴胺能网络和大规模网络（即前默认模式网络[ADMN]、执行网络[ECN]和前凸显网络[aSAN]）中，ADHD-CoUD患者比CoUD患者具有更保留的代谢连通性。我们证明了ADHD-CoUD患者和CoUD患者物质使用行为背后存在不同的神经病理学基础。此外，我们提供了支持自我用药假说的神经生物学证据，表明ADHD-CoUD患者可能会体验到服用可卡因的短期益处（即补偿多巴胺能缺陷和相关的认知行为缺陷）。
