Supplementary Material for: Dysregulation of plasma growth factors and chemokines in cocaine use disorder: Implications for dual diagnosis with schizophrenia and antisocial personality disorder in an exploratory study

Introduction: Dual diagnosis in individuals with cocaine use disorders (CUD) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD).
Methods: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N=25) or as a dual diagnosis (DD group. N=30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis.
Results: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis.
Conclusions: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

引言：合并双重诊断（dual diagnosis）的可卡因使用障碍（Cocaine Use Disorders, CUD）患者群体，其心理健康挑战表现为致残性疾病易感性升高与过早死亡率上升。尽管学界针对抑郁与焦虑已开展大量研究，但其他常见共病如精神病性障碍与人格障碍所受关注却相对不足。本研究探讨炎症相关介质作为CUD合并精神分裂症（schizophrenia, SCZ）或反社会人格障碍（antisocial personality disorder, APD）双重诊断的潜在生物标志物的可能性。

方法：本探索性研究共纳入95名受试者，其中包括40名健康对照者与55名处于戒断状态的CUD患者。终生CUD诊断分为单一诊断组（CUD组，N=25）与双重诊断组（dual diagnosis, DD），N=30，后者又细分为CUD合并SCZ亚组（CUD+SCZ）与CUD合并APD亚组（CUD+APD）。对所有受试者进行临床评估，并检测其血浆中生长因子（即G-CSF、BDNF与VEGF-A）及趋化因子（即CCL11/eotaxin-1、CCL2/MCP-1与CXCL12/SDF-1）的浓度，检测结果经log(10)转换后用于统计分析。

结果：生长因子与趋化因子的表达失调情况与CUD及精神疾病诊断相关。具体而言，CUD组患者的G-CSF与CCL11/eotaxin-1浓度显著低于健康对照组。与之相对，双重诊断组患者的所有检测物浓度均显著高于CUD组与健康对照组。此外，双重诊断组内的CUD+SCZ与CUD+APD亚组间，上述检测物浓度无显著差异。针对可卡因相关变量的分析显示，CUD组中存在显著关联：首次使用可卡因的年龄与BDNF及CCL2/MCP-1浓度呈负相关；可卡因戒断时长与BDNF及CCL11/eotaxin-1浓度呈正相关。最后，纳入所有上述检测物的逻辑回归模型，在区分单纯CUD患者与双重诊断患者时展现出优异的判别效能。

结论：合并CUD双重诊断的患者，其体内生长因子与趋化因子浓度升高，这一特征可将其与单纯CUD患者区分开来。目前尚不清楚这些炎症介质的差异是否仅与SCZ和APD的共病状态相关。本研究揭示了潜在的生物标志物及相关关联，为阐明CUD与精神疾病间的复杂相互作用、优化临床诊断与治疗方案提供了有价值的见解。