Psychoneuroendocrinology. 2025 Oct 15;182:107653. doi: 10.1016/j.psyneuen.2025.107653. Online ahead of print.
ABSTRACT
INTRODUCTION: Allostatic load (AL), a cumulative measure of stress, has been implicated in the pathophysiology of major depressive disorder (MDD). However, the relationship between AL and depressive symptoms, treatment response, and metabolic health remains unclear.
METHODS: This study investigated AL in unmedicated (>6 weeks) inpatients with MDD (n = 31) at baseline and after 6 weeks of treatment with either Venlafaxine or Mirtazapine. Baseline patients were compared to age- and sex-matched healthy controls. Depressive symptoms and functional status were assessed using the Hamilton Scale for Depression (HAMD) and Global Assessment of Functioning (GAF) rating scales. Furthermore, metabolic syndrome (MetS) was assessed in the MDD patients at baseline and Week 6.
RESULT: Our findings indicate that AL was significantly elevated in MDD patients compared to healthy controls (HCs; n = 31) at baseline (p = 0.031). AL was not associated with functional status at baseline or at Week 6. MetS was prevalent among MDD patients but was not correlated with clinical symptom severity. Lastly, AL significantly (p = 0.02) decreased after 6 weeks of antidepressant treatment, although the reduction was not predictive of symptom improvement or functional remission.
DISCUSSION/CONCLUSION: These findings suggest that AL reflects underlying multisystem dysregulation in MDD rather than symptom severity or treatment responsiveness. The observed decrease in AL during treatment may indicate an effect of antidepressants, although further research with longer follow-up is needed. The observed potential sex difference in AL warrants further investigation using larger sample sets.
PMID:41108944 | DOI:10.1016/j.psyneuen.2025.107653
