Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga , Málaga , Spain.
Centro Provincial de Drogodependencia, Diputación de Málaga , Málaga , Spain.
Front Psychiatry. 2015 Feb 16;6:17. doi: 10.3389/fpsyt.2015.00017. eCollection 2015.
There are sex differences in the progression of drug addiction, relapse, and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine. Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women) and 73 healthy controls (48 men and 25 women) were clinically assessed with the diagnostic interview "Psychiatric Research Interview for Substance and Mental Disorders." Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines, and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex, controlling for covariates age and body mass index (BMI). Relationships between these concentrations and variables related to cocaine addiction were also analyzed in addicted subjects. The results showed that the concentrations of chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1) were only affected by history of cocaine addiction. The plasma concentrations of interleukin 1-beta (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNFα) were affected by history of cocaine addiction and sex. In fact, whereas cytokine concentrations were higher in control women relative to men, these concentrations were reduced in cocaine-addicted women without changes in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative, whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were decreased. Interestingly, N-palmitoleoyl-ethanolamine (POEA) was only increased in cocaine-addicted women. The covariate BMI had a significant effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes.
在药物成瘾的进展、复发和对治疗的反应方面存在性别差异。由于生物因素参与了这些差异，因此在使用成瘾生物标志物时应考虑这些差异。在本研究中，我们评估了精神共病的性别差异，以及已报道受可卡因影响的血浆介质的浓度。55 名禁欲可卡因成瘾受试者被诊断为终生可卡因使用障碍（40 名男性和 15 名女性）和 73 名健康对照者（48 名男性和 25 名女性）接受了“精神药物和物质使用障碍的精神病学研究访谈”的临床评估。根据可卡因使用史和性别分析了趋化因子、细胞因子、N-酰基-乙醇胺和 2-酰基-甘油的血浆浓度，同时控制了协变量年龄和体重指数（BMI）。还分析了成瘾受试者中这些浓度与与可卡因成瘾相关的变量之间的关系。结果表明，趋化因子（C-C 基序）配体 2/单核细胞趋化蛋白-1（CCL2/MCP-1）和趋化因子（C-X-C 基序）配体 12/基质细胞衍生因子-1（CXCL12/SDF-1）的浓度仅受可卡因使用史的影响。白细胞介素 1-β（IL-1β）、IL-6、IL-10 和肿瘤坏死因子-α（TNFα）的血浆浓度受可卡因使用史和性别影响。事实上，与男性相比，对照女性的细胞因子浓度更高，但这些浓度在可卡因成瘾女性中降低，而男性中没有变化。关于脂肪酸衍生物，可卡因使用史对每种酰基衍生物的浓度有主要影响，而 N-酰基-乙醇胺总体上在可卡因组中增加，2-酰基-甘油减少。有趣的是，只有可卡因成瘾女性的 N-棕榈油酸基-乙醇胺（POEA）增加。协变量 BMI 对 POEA 和 N-花生四烯酸基-乙醇胺浓度有显著影响。关于可卡因组的精神共病，女性的物质使用障碍共病发生率低于男性。例如，80%的男性和 40%的女性存在酒精使用障碍。相比之下，可卡因成瘾女性的共患精神障碍（即心境、焦虑和精神病障碍）患病率增加。此外，可卡因成瘾受试者的 N-硬脂酰-乙醇胺和 2-亚油酰-甘油浓度与精神共病诊断之间存在关系。这些结果表明，血浆可卡因成瘾生物标志物存在性别影响，以及共患精神病理学的存在对临床目的具有重要意义。
