Serum Serotonin Levels and Postpartum Depression in Women with Gestational Diabetes Mellitus: A Prospective Psychobiological Study

Background/Objectives: Gestational diabetes mellitus (GDM) is an established risk factor for postpartum depression (PPD), yet its psychobiological mechanisms remain poorly characterized. This study aimed to profile the psychological and biochemical-associated factors of PPD among women with GDM in Jordan. Methods: A prospective observational study recruited 204 pregnant women from three Jordanian hospitals. The Edinburgh Postnatal Depression Scale (EPDS) was administered antepartum and at 4–9 weeks postpartum, with EPDS ≥ 13 used to define probable PPD. Antepartum serum serotonin, cortisol, and CRP were measured by ELISA in a biomarker subsample of 115 participants (84 non-GDM and 31 GDM). Of 54 women diagnosed with GDM, 44 completed the postpartum EPDS and were included in the within-GDM psychological analysis; 25 of these also had stored antepartum serum and were included in the within-GDM biomarker analysis. Analyses were exploratory, consistent with a pilot design. Results: Probable PPD was identified in 26 of 44 GDM women (59.1%). GDM status did not predict PPD in the full cohort (p = 0.237). Within the GDM subgroup, women with probable PPD had significantly higher antepartum EPDS scores (p = 0.003), and elevated perceived stress (p = 0.049), than those without probable PPD. In the within-GDM biomarker subsample (n = 25), antepartum serum serotonin was significantly lower in women with probable PPD (p < 0.001); CRP and cortisol did not differ significantly. Serotonin and cortisol showed the strongest inverse correlations with postpartum EPDS (both p < 0.01). Among GDM women without antepartum depression, 19.0% developed new-onset PPD. Conclusions: In our study, GDM women who develop probable PPD exhibit a distinct profile of antenatal vulnerability and lower serum serotonin levels. Routine perinatal mental health screening and biomarker investigation are warranted in this high-risk group. Findings should be confirmed in larger, adequately powered cohorts.