Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
Transl Psychiatry. 2023 Apr 18;13(1):127. doi: 10.1038/s41398-023-02426-1.
Rates of return to use in addiction treatment remain high. We argue that the development of improved treatment options will require advanced understanding of individual heterogeneity in Substance Use Disorders (SUDs). We hypothesized that considerable individual differences exist in the three functional domains underlying addiction-approach-related behavior, executive function, and negative emotionality. We included N = 593 participants from the enhanced Nathan Kline Institute-Rockland Sample community sample (ages 18-59, 67% female) that included N = 420 Controls and N = 173 with past SUDs [54% female; N = 75 Alcohol Use Disorder (AUD) only, N = 30 Cannabis Use Disorder (CUD) only, and N = 68 Multiple SUDs]. To test our a priori hypothesis that distinct neuro-behavioral subtypes exist within individuals with past SUDs, we conducted a latent profile analysis with all available phenotypic data as input (74 subscales from 18 measures), and then characterized resting-state brain function for each discovered subtype. Three subtypes with distinct neurobehavioral profiles were recovered (p < 0.05, Cohen's D: 0.4-2.8): a "Reward type" with higher approach-related behavior (N = 69); a "Cognitive type" with lower executive function (N = 70); and a "Relief type" with high negative emotionality (N = 34). For those in the Reward type, substance use mapped onto resting-state connectivity in the Value/Reward, Ventral-Frontoparietal and Salience networks; for the Cognitive type in the Auditory, Parietal Association, Frontoparietal and Salience networks; and for the Relief type in the Parietal Association, Higher Visual and Salience networks (p < 0.05). Subtypes were equally distributed amongst individuals with different primary SUDs (χ = 4.71, p = 0.32) and gender (χ = 3.44, p = 0.18). Results support functionally derived subtypes, demonstrating considerable individual heterogeneity in the multi-dimensional impairments in addiction. This confirms the need for mechanism-based subtyping to inform the development of personalized addiction medicine approaches.
成瘾治疗的回报率仍然很高。我们认为，开发更好的治疗方法需要对物质使用障碍（SUD）个体异质性有深入的了解。我们假设，成瘾相关行为、执行功能和负性情绪这三个功能领域存在相当大的个体差异。我们纳入了增强的 Nathan Kline Institute-Rockland 样本社区样本（年龄 18-59 岁，67%为女性）中的 593 名参与者，其中包括 420 名对照者和 173 名有过去 SUD 病史的参与者（54%为女性；75 名仅有酒精使用障碍（AUD），30 名仅有大麻使用障碍（CUD），68 名有多种 SUD）。为了检验我们的假设，即过去有 SUD 病史的个体中存在不同的神经行为亚型，我们对所有可用的表型数据（来自 18 项测量的 74 个子量表）进行了潜在剖面分析，然后对每个发现的亚型的静息态脑功能进行了特征描述。恢复了具有不同神经行为特征的三种亚型（p<0.05，Cohen's D：0.4-2.8）：一种具有更高成瘾相关行为的“奖励型”（N=69）；一种具有较低执行功能的“认知型”（N=70）；以及一种具有高负性情绪的“缓解型”（N=34）。对于奖励型，物质使用与价值/奖励、腹侧额顶叶和突显网络的静息状态连通性有关；对于认知型，物质使用与听觉、顶叶联合、额顶叶和突显网络有关；对于缓解型，物质使用与顶叶联合、高级视觉和突显网络有关（p<0.05）。不同原发性 SUD 和性别（χ2=4.71，p=0.32；χ2=3.44，p=0.18）的个体中，亚型分布均匀。结果支持功能衍生的亚型，表明成瘾的多维障碍存在相当大的个体异质性。这证实了需要基于机制的亚型划分，为个性化成瘾医学方法的发展提供信息。
