Imperial College London, Neuropsychopharmacology Unit, 2nd Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London, W12 0NN, United Kingdom.
Transl Psychiatry. 2024 Nov 9;14(1):467. doi: 10.1038/s41398-024-03159-5.
Most addiction research has focused on reward- and impulsivity-related neurocircuitry. However, the impact of the withdrawal/negative affect stage in the addiction cycle has been somewhat overlooked, despite it being commonly evident in the clinic. This stage crucially drives negative reinforcement of repeated drug use and relapse, yet less is known about its neural underpinnings. How negative emotional processing is dysregulated in substance dependence is incompletely understood and may manifest differentially across the types of substances. In turn, the regions involved in negative emotional processing may show different patterns of dysregulation. Understanding how neurocircuitry involved in negative states differs across various substances may help inform new targets for treatments. Following a comprehensive literature search of studies examining negative emotional processing in substance dependence, a quantitative approach was deemed inappropriate. Instead, we employed a narrative approach to exploring neural responses to tasks involving emotional processing in alcohol, cocaine, opioid and cannabis dependence. Regions that were found to be dysregulated included the amygdala, insula, anterior cingulate, and medial prefrontal cortex. However, patterns of reactivity differed across alcohol, cocaine, opioid and cannabis dependence. Brain activation in alcohol dependence broadly appeared blunted in response to negative affective stimuli and emotional faces, whilst conversely appeared heightened in cocaine dependence. In opioid dependence, the amygdala was consistently implicated, whilst the insula, anterior cingulate, and medial prefrontal cortex were implicated in cannabis dependence. However, there was wide variability amongst the studies, with very few studies investigating opioid and cannabis dependence. These findings suggest emotional dysregulation varies according to the type of substance dependence. However, the variability in findings and lack of studies highlights the need for more research in this area. Further characterisation of emotional dysregulation in substance dependence will enable identification of treatment targets. More targeted treatments that modulate negative emotional processing could substantially improve outcomes by aiding relapse prevention.
大多数成瘾研究都集中在奖励和冲动相关的神经回路。然而，尽管在临床上普遍存在，但成瘾周期的戒断/负性情绪阶段的影响在某种程度上被忽视了。这个阶段是导致重复使用药物和复发的负强化的关键因素，但对其神经基础的了解较少。物质依赖中负面情绪处理是如何失调的还不完全清楚，并且可能在不同类型的物质中表现不同。反过来，涉及负面情绪处理的区域可能表现出不同的失调模式。了解不同物质依赖中涉及负面状态的神经回路有何不同，可能有助于为治疗提供新的目标。在对研究物质依赖中负面情绪处理的文献进行全面搜索后，认为定量方法不适用。相反，我们采用叙述性方法来探讨涉及酒精、可卡因、阿片类药物和大麻依赖中情绪处理的任务的神经反应。发现失调的区域包括杏仁核、脑岛、前扣带回和内侧前额叶皮质。然而，对酒精、可卡因、阿片类药物和大麻依赖的反应模式不同。与可卡因依赖相比，酒精依赖的大脑激活在对负性情绪刺激和情绪面孔的反应中普遍减弱。相反，在可卡因依赖中，大脑激活增强。在阿片类药物依赖中，杏仁核一直被牵连，而脑岛、前扣带回和内侧前额叶皮质则与大麻依赖有关。然而，研究之间存在很大的差异，很少有研究调查阿片类药物和大麻依赖。这些发现表明，情绪失调根据物质依赖的类型而有所不同。然而，发现结果的可变性和缺乏研究突出了该领域需要更多的研究。进一步描述物质依赖中的情绪失调将能够确定治疗目标。更有针对性的调节负面情绪处理的治疗方法可以通过帮助预防复发来显著改善结果。
