1Turku Brain and Mind Center, University of Turku, Turku, Finland.
2Clinical Neurosciences, University of Turku, Turku, Finland.
J Behav Addict. 2023 Aug 9;12(3):670-681. doi: 10.1556/2006.2023.00037. Print 2023 Oct 5.
The neurobiological mechanisms of gambling disorder are not yet fully characterized, limiting the development of treatments. Defects in frontostriatal connections have been shown to play a major role in substance use disorders, but data on behavioral addictions, such as gambling disorder, are scarce. The aim of this study was to 1) investigate whether gambling disorder is associated with abnormal frontostriatal connectivity and 2) characterize the key neurotransmitter systems underlying the connectivity abnormalities.
Fifteen individuals with gambling disorder and 17 matched healthy controls were studied with resting-state functional connectivity MRI and three brain positron emission tomography scans, investigating dopamine (18F-FDOPA), opioid (11C-carfentanil) and serotonin (11C-MADAM) function. Frontostriatal connectivity was investigated using striatal seed-to-voxel connectivity and compared between the groups. Neurotransmitter systems underlying the identified connectivity differences were investigated using region-of-interest and voxelwise approaches.
Individuals with gambling disorder showed loss of functional connectivity between the right nucleus accumbens (NAcc) and a region in the right dorsolateral prefrontal cortex (DLPFC) (PFWE <0.05). Similarly, there was a significant Group x right NAcc interaction in right DLPFC 11C-MADAM binding (p = 0.03) but not in 18F-FDOPA uptake or 11C-carfentanil binding. This was confirmed in voxelwise analyses showing a widespread Group x right NAcc interaction in the prefrontal cortex 11C-MADAM binding (PFWE <0.05). Right NAcc 11C-MADAM binding potential correlated with attentional impulsivity in individuals with gambling disorder (r = -0.73, p = 0.005).
Gambling disorder is associated with right hemisphere abnormal frontostriatal connectivity and serotonergic function. These findings will contribute to understanding the neurobiological mechanism and may help identify potential treatment targets for gambling disorder.
赌博障碍的神经生物学机制尚未完全阐明，这限制了治疗方法的发展。已有研究表明，前额叶-纹状体连接缺陷在物质使用障碍中起主要作用，但关于行为成瘾（如赌博障碍）的数据却很少。本研究旨在：1）探讨赌博障碍是否与前额叶-纹状体连接异常有关；2）描述连接异常背后的关键神经递质系统。
本研究纳入 15 名赌博障碍患者和 17 名匹配的健康对照者，使用静息态功能磁共振成像和三种脑正电子发射断层扫描技术，研究多巴胺（18F-FDOPA）、阿片（11C-卡芬太尼）和 5-羟色胺（11C-MADAM）功能。使用纹状体种子点到体素连接的方法研究前额叶-纹状体连接，并比较两组之间的差异。使用基于感兴趣区和体素的方法，研究了确定的连接差异背后的神经递质系统。
与健康对照组相比，赌博障碍患者右侧伏隔核（NAcc）与右侧背外侧前额叶皮质（DLPFC）区域之间的功能连接降低（PFWE <0.05）。同样，在右侧 DLPFC 区域 11C-MADAM 结合上也存在显著的组间×右侧 NAcc 交互作用（p = 0.03），但在 18F-FDOPA 摄取或 11C-卡芬太尼结合上没有。这在体素水平分析中得到了进一步证实，在右侧 NAcc 11C-MADAM 结合上显示出广泛的组间×右侧 NAcc 交互作用（PFWE <0.05）。赌博障碍患者的右侧 NAcc 11C-MADAM 结合与注意力冲动性呈负相关（r = -0.73，p = 0.005）。
赌博障碍与右侧半球异常的前额叶-纹状体连接和 5-羟色胺能功能有关。这些发现将有助于理解神经生物学机制，并可能有助于确定赌博障碍的潜在治疗靶点。
