BACKGROUND Chronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. METHOD At baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. RESULTS At baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. CONCLUSION Our findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches.

中文翻译：

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可卡因使用者的精神症状和糖皮质激素受体基因的表达：一项纵向研究。

背景长期可卡因使用者（CU）显示糖皮质激素受体基因（NR3C1）的外周表达降低，这可能与CU中经常发生的与压力有关的精神症状有关。然而，尚不清楚精神症状和较低的NR3C1表达是否相互关联，以及减少药物消耗是否会逆转它们。方法在基线时，在68个娱乐性CU，30个依赖型CU和68个单纯刺激的对照组中测量了NR3C1 mRNA的表达。此外，还评估了修订后的症状清单（SCL-90R）和Barratt冲动量表（BIS）。在为期一年的随访中，在48位未接受兴奋剂的对照组，增加了19 CU和减少了消费的19 CU中检查了NR3C1表达的变化与精神病症状之间的关系。在两次测试中 测定头发样品中的可卡因浓度。使用混合效应模型研究药物使用强度的变化如何随时间影响精神症状和NR3C1表达的严重程度。结果基线时，在大多数SCL-90R分量表中，娱乐性和依赖性CU表现出较高的冲动性和相当大的症状负担。在几个冲动得分，SCL-90R全球严重程度指数，偏执思想和抑郁量表以及NR3C1表达中发现了时间组相互作用的影响。配对比较显示，在这些SCL-90R子量表中，降低的CU尤其得到改善，而对它们的NR3C1表达进行了调整。最后，NR3C1表达的变化与冲动的变化呈负相关，但与SCL-90R分数没有负相关。