Increased adrenocorticotropic hormone (ACTH) levels predict severity of depression after six months of follow-up in outpatients with major depressive disorder

Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depressive disorder (MDD). Outpatients diagnosed with MDD (n = 199) underwent psychological evaluation, and were followed up with a phone interview after 6 months, using the Patient Health Questionnaire (PHQ-9). At 6-month follow-up, 59 out of 199 patients with MDD were still depressed (29.5%), as shown by scores ≥ 10 on the PHQ-9. The depressed group at follow-up showed significantly higher anxiety and suicidality levels at baseline than the non-depressed group at follow-up. Among the complete blood counts, lipid profiles, and hormone levels, adrenocorticotropic hormone (ACTH) was the only parameter that was significantly increased in the still depressed group. Levels higher than 40 pg/mL of ACTH at baseline were associated with higher depression scores at follow-up. Multiple linear regression analyses revealed that ACTH and cortisol predicted depression scores at follow-up, after controlling for baseline depression scores. Increased ACTH level at baseline may predict ongoing symptoms and severity of depression at follow-up, suggesting the role of dysfunctional HPA axis in MDD prognosis.