Major depressive disorder (MDD) is a leading cause of disability worldwide and remains difficult to diagnose and monitor due to the lack of reliable biomarkers. Current diagnostic tools rely on subjective, questionnaire-based assessments. Although MDD has been linked to impairment in several biological processes, including the HPA axis and neuronal transmission, no circulating biomarker has been validated to reflect depressive states or treatment response objectively. My research explores a potential novel biomarker for MDD, a molecule expressed by cells implicated in depressive pathology. Our unpublished data indicate that this molecule is upregulated by neurons in a murine model of MDD. Notably, this molecule can be detected in both plasma and cerebrospinal fluid (CSF), positioning it as a promising candidate for a measurable, non-invasive biomarker. We hypothesize that the expression of this molecule correlates with depression severity and could serve both diagnostic and therapeutic roles. To test this, my study focuses on four specific aims: (1) quantify its levels in plasma and CSF of depression-like mice; (2) correlate its levels with behavioral outcomes, stress susceptibility, and antidepressant response; (3) measure it in clinical samples from patients with MDD, PTSD; and (4) evaluate whether blocking this molecule alleviates depressive symptoms. Using chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models, we have observed a dynamic increase in this molecule’s levels in stress-sensitive mice. These preliminary findings suggest this molecule may serve as a biomarker for MDD and related disorders. This work could significantly improve the current diagnosis process and treatment of depression.

Supervisor: Dr. Gali Umschweif-Nevo