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Aims: Gender and psychiatric comorbidity seem to influence patients' inter-individual response to Opioid Substitution Treatments (OST) in Opioid Use Disorder (OUD) management. The aim of the study was to assess psychopathological dimensions in an Italian sample of OUD individuals entering a methadone/buprenorphine maintenance program; secondary, we evaluated the possible gender-specific differences within the psychopathological profiles.Methods: In a cross-sectional study, we recruited 1052 (792 male; 260 female) OUD subjects receiving OST. All patients underwent a clinical and psychometric evaluation assessing demographics, psychiatric history, psychopathological features via the Symptom Checklist-90-Revised (SCL-90-R), and were prescribed psychopharmacological treatments.Results: Our results reveal gender-specific differences in a real-world sample of opioid-maintained OUD individuals attending public addiction services in Italy. Compared to men, women reported higher scores in both General Symptomatic Index (GSI) and in all the SCL-90-R sub-scales. No impact of pharmacological treatment was detected. Finally, regression analysis revealed that being in methadone-maintenance group was significantly associated with high GSI scores in the male, but not female, group.Conclusions: Increasing the knowledge of psychopathological dimensions in patients with OST, with relevance to gender differences, is important for a better understanding of factors that influence the outcome and for further development in gender-tailored strategies. [ABSTRACT FROM AUTHOR]