The Relationship Between Serum Neurosteroids and Oxytocin Levels and Craving, Aggression and Emotion Regulation in Patients with Methamphetamine Use Disorder

Background: This study aimed to investigate the relationship between serum neuroactive steroids (NAS) and oxytocin and craving and psychosocial functioning in men diagnosed with methamphetamine use disorder (MUD). Methods: In this observational cross-sectional study, 40 men with MUD (PG) and 41 non-substance-use-disorder controls (CG) completed measures of emotion dysregulation (DERS-16), attachment (ECR-R), aggression (BPAQ), and suicidal ideation (BSS). PG additionally completed the Substance Craving Scale (SCS) and Addiction Profile Index (API). Serum allopregnanolone (ALLO), DHEAS, testosterone, 17β-estradiol (E2), and oxytocin were assayed. Results: The results indicated that the PG exhibited significantly higher scores than the CG across all psychological measures. Robust adjusted group effects were observed for DERS-16 (Model 1: F = 35.507, p < 0.001; Model 2: F = 18.225, p < 0.001) and trait anger (Model 1: F = 41.104, p < 0.001; Model 2: F = 16.732, p < 0.001). Notably, serum levels of ALLO, DHEAS, testosterone, E2, and oxytocin did not differ significantly between groups. However, hormonal measures were strongly intercorrelated within both groups (r ≈ 0.877–0.936, all p < 0.001). In the PG, craving demonstrated positive correlations with DHEAS (r = 0.384, p = 0.014), testosterone (r = 0.415, p = 0.008), E2 (r = 0.360, p = 0.023), and oxytocin (r = 0.350, p = 0.027). A multivariable model analyzing craving was statistically significant (R2 = 0.350; F(3,36) = 6.474, p = 0.001), with composite hormonal factor (B = 2.390, p = 0.016) serving as an independent predictor, while API Excluding Craving(API-EC) (p = 0.094) and DERS-16 did not emerge as a significant factor (p = 0.056). In hormone-specific models controlling for API-EC and DERS-16, DHEAS (p = 0.012), testosterone (p = 0.007), oxytocin (p = 0.023), and E2 (p = 0.023) retained significance after false discovery rate (FDR) correction; ALLO did not (p = 0.055). Conclusions: Despite the absence of significant differences in peripheral NAS and oxytocin levels between groups, men with MUD exhibited pronounced psychosocial impairments. The craving experienced during inpatient treatment was primarily elucidated by an integrated endocrine profile. These findings underscore the necessity for larger longitudinal studies incorporating repeated hormonal assessments to further explore these relationships.