Department of Radiology, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha, Hunan 410011, PR China.
School of Life Science and Technology, Xidian University, No. 266 Xinglong Section of Xifeng Road, Xi'an, Shaanxi 710126, PR China.
Cereb Cortex. 2024 Apr 1;34(4). doi: 10.1093/cercor/bhae169.
Higher sensitivity to reward (SR) and weaker sensitivity to punishment (SP) construct the fundamental craving characteristics of methamphetamine abuse. However, few studies have appraised relationships between SR/SP (SR or SP) and cortical morphological alterations in methamphetamine abusers and whether hereditary factors take effects on SR/SP is unclear. Based on surface-based morphometric analysis, cortical discrepancy was investigated between 38 methamphetamine abusers and 37 healthy controls. Within methamphetamine abusers, correlation profiling was performed to discover associations among aberrant neuroimaging substrates, SR, SP, and craving. According to nine single nucleotide polymorphism sites of dopamine-related genes, we conducted univariate general linear model to find different effects of genotypes on cortical alterations and SR/SP/craving (SR, SP, or craving). Ultimately, mediation analyses were conducted among single nucleotide polymorphism sites, SR/SP/craving, and cortical morphological alterations to discover their association pathways. Compared to healthy controls, thinner cortices in inferior temporal gyrus, lateral orbitofrontal cortex, medial orbitofrontal cortex, inferior parietal lobule, and lateral occipital cortex in the left hemisphere were found in methamphetamine abusers (P < 0.05, family-wise error corrected). Cortical thickness in the inferior temporal gyrus was negatively correlated with SR scores. We found that rs1800497 A-containing genotypes had lower cortical thickness in the left inferior parietal lobule than the GG genotype. The rs5751876 had effects on SR scores. This study would provide convincing biomarkers for SR in methamphetamine abusers and offer potential genetic targets for personalizing relapse prevention.
更高的奖赏敏感性（SR）和较弱的惩罚敏感性（SP）构成了冰毒滥用的基本成瘾特征。然而，很少有研究评估过冰毒滥用者的 SR/SP（SR 或 SP）与皮质形态改变之间的关系，以及遗传因素是否对 SR/SP 有影响。本研究基于表面形态计量学分析，比较了 38 名冰毒滥用者和 37 名健康对照者的皮质差异。在冰毒滥用者中，进行了相关分析，以发现异常神经影像学底物、SR、SP 和渴求之间的关联。根据九个与多巴胺相关基因的单核苷酸多态性位点，我们进行了单变量一般线性模型，以发现不同基因型对皮质改变和 SR/SP/渴求（SR、SP 或渴求）的不同影响。最终，在单核苷酸多态性位点、SR/SP/渴求与皮质形态改变之间进行了中介分析，以发现它们之间的关联途径。与健康对照组相比，冰毒滥用者左侧颞下回、外侧眶额皮质、内侧眶额皮质、下顶叶和外侧枕叶皮质的皮质较薄（P<0.05，经家族错误校正）。颞下回的皮质厚度与 SR 评分呈负相关。我们发现，rs1800497 载有 A 等位基因的基因型比 GG 基因型的左侧顶下小叶皮质厚度较低。rs5751876 对 SR 评分有影响。本研究将为冰毒滥用者的 SR 提供有说服力的生物标志物，并为个性化预防复发提供潜在的遗传靶点。
