Clinical and inflammatory profiles in substance use disorder: gender, substance type, and comorbidity in a...

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.

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.

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.

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.