Clinical and inflammatory profiles in substance use disorder: gender, substance type, and comorbidity in a single-center cross-sectional study in Turkey

BACKGROUND: Substance use disorder (SUD) is associated with systemic inflammation and cognitive vulnerability. Peripheral biomarkers may help characterize biological risk across substances and comorbidities. Turkey has experienced a recent rise in methamphetamine and pregabalin misuse, underscoring the need for biomarker-based clinical profiling. METHODS: A total of 321 inpatients were evaluated in a single inpatient addiction treatment unit in Turkey (2019-2025). Exclusion criteria included severe somatic disease, preexisting psychiatric diagnoses, and incomplete records. Admission data included demographics, primary substance, DSM-5 comorbidities, biomarkers (C-reactive protein [CRP], neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Systemic Immune-Inflammation Index, Hemoglobin × Albumin/Leukocyte × Platelet Index, Inflammatory Burden Index [IBI]). Analyses used appropriate parametric/non-parametric tests, analysis of covariance, and logistic regression adjusted for age, sex, and comorbidities. RESULTS: IBI and CRP differed significantly across substance groups, with higher inflammatory burden among methamphetamine, alcohol, and MDMA users. After multiple-comparison correction, IBI remained statistically significant, whereas CRP required cautious interpretation. Longer duration of use correlated with higher inflammatory burden. Depressive (14.6%) and anxiety disorders (16.2%) were the most common comorbidities. Bipolar disorder, although infrequent, clustered with higher inflammatory markers. Gender patterns reflected international trends, with greater alcohol/cannabis use in male and earlier, faster dependence progression in female. Multivariate models showed that methamphetamine and alcohol independently predicted elevated IBI after adjustment. CONCLUSIONS: IBI and CRP appear to be the most sensitive indicators of systemic inflammation in SUD, particularly in stimulant and alcohol users. Elevation of IBI supports its potential role as a cognition-related biomarker. Findings highlight biological heterogeneity across substances, genders, and comorbidities, and emphasize the need for future prospective studies with neurocognitive testing and structured tobacco documentation.