Orexinergic Dysregulation in Major Depressive Disorder: Insights from a Prospective Cohort Study Evaluating MADRS,...

Major depressive disorder (MDD) is a complex psychiatric condition characterized by affective, cognitive, and somatic symptoms. Disturbances in sleep and cognition are common yet underexplored features of MDD. Orexin, a hypothalamic neuropeptide, plays key roles in arousal, sleep-wake regulation, and cognition. This was a prospective, observational study with longitudinal follow-up investigating the correlation between serum orexin-A levels and depression symptom severity, sleep quality, and cognitive status, as assessed with standard psychometric tools.

A total of 113 patients with MDD and 60 age- and sex-matched healthy controls were assessed in this study. Patients were followed up after 6-12 weeks of antidepressant therapy. Symptom severity, sleep quality, and cognitive status were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Pittsburgh Sleep Quality Index (PSQI), and the Montreal Cognitive Assessment (MoCA), respectively. Serum orexin-A was quantified using an enzyme-linked immunosorbent assay (ELISA). The correlation between changes in serum orexin-A levels and clinical scale scores was assessed.

The median (Q1-Q3) serum orexin levels in patients and healthy controls were 192.6 (183.2-209.3) pg/mL and 207.4 (203.8-218.7) pg/mL, respectively, with a statistically significant difference (p < .001). Serum orexin-A levels in the patient group at baseline and follow-up were not statistically significant. Changes in various score components of the questionnaires were statistically significant. However, serum orexin-A levels were correlated only with the apparent sadness component of MADRS. No correlation was observed between orexin-A levels and PSQI or MoCA questionnaire components.

Serum orexin-A showed potential as a biomarker for MDD, exhibiting correlation with a MADRS score component. However, no correlation was observed with sleep quality and cognitive status, necessitating validation in larger cohorts.