National Institute on Drug Dependence, Peking University, Beijing, China.
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Addict Biol. 2020 Jan;25(1):e12709. doi: 10.1111/adb.12709. Epub 2019 Feb 28.
Methamphetamine (MA)-related psychiatric symptoms (MAP) are serious comorbidities of MA use and result in many social problems such as violence and suicide. We investigated the sociodemographic and genetic risk factors for persistent MAP of MA users (MUs) and constructed an early MAP prediction model. Derivation and replication samples had 1734 and 905 MUs, respectively. Symptom Checklist 90, Childhood Trauma Questionnaire, Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV, and Social Support Rating Scale were used to assess the past-year prevalence of general MAP and life events retrospectively. Genome-wide association study (GWAS) was used to analyze MAP-related genetic factors. The prediction model was constructed by integrating the risk life events and clinical and genetic features using logistic regression. Of the 2639 MUs, 1293 (48.83%) had past-year MAP. The severity of MA addiction (SMA), childhood trauma, childhood ADHD symptoms, and social support were reliable risk factors for persistent MAP. By integrating these risk factors and the polygenic risk score from GWAS from derivation samples, the area under the curve (AUC) of the predictive model for MAP was 0.754 (95% CI 0.717~0.771). The risk factors and prediction model were also verified in replication samples. In addition, SMA, ADHD, and social support were mediators for the effect of the risk genetic factor on persistent MAP. Our study identified several risk factors for persistent MAP and will be helpful for developing scalable tools for the prevention of persistent and general MAP.
甲基苯丙胺（MA）相关的精神症状（MAP）是 MA 使用的严重合并症，导致许多社会问题，如暴力和自杀。我们调查了 MA 使用者（MUs）持续 MAP 的社会人口学和遗传风险因素，并构建了早期 MAP 预测模型。推导和复制样本分别有 1734 和 905 名 MUs。使用症状清单 90、儿童创伤问卷、注意缺陷多动障碍（ADHD）评定量表-IV 和社会支持评定量表回顾性评估过去一年一般 MAP 和生活事件的患病率。全基因组关联研究（GWAS）用于分析与 MAP 相关的遗传因素。通过逻辑回归将风险生活事件以及临床和遗传特征整合到预测模型中。在 2639 名 MUs 中，有 1293 名（48.83%）在过去一年中有 MAP。MA 成瘾严重程度（SMA）、儿童创伤、儿童 ADHD 症状和社会支持是持续 MAP 的可靠风险因素。通过整合这些风险因素和推导样本中来自 GWAS 的多基因风险评分，MAP 预测模型的曲线下面积（AUC）为 0.754（95%CI 0.717~0.771）。在复制样本中也验证了这些风险因素和预测模型。此外，SMA、ADHD 和社会支持是风险遗传因素对持续 MAP 影响的中介因素。我们的研究确定了持续 MAP 的几个风险因素，这将有助于开发用于预防持续和一般 MAP 的可扩展工具。
