NEGR1 can influence symptom severity in fluoxetine treated major depression disorder patients

Background and Objectives: Neuronal growth regulator 1 (NEGR1) is a cell adhesion molecule of immunoglobulin (Ig) superfamily related to IgLON subgroup. NEGR1 promotes cell-cell adhesion, stimulates neurite growth of hypothalamic neurons and involves synapse formation. NEGR1 is a key genomic locus associated with major depressive disorder (MDD) and its functional role on MDD is still unknown. This study aimed to examine the impact of fluoxetine, a selective serotonin reuptake inhibitor, on NEGR1 expression in MDD patients, and to explore the association between NEGR1 expression levels and the severity of depressive symptoms. Method: In this case-control study, NEGR1 mRNA expression in fluoxetine-treated and non-treated cultured peripheral blood mononuclear cells (PBMC) were detected by qRT-PCR in 40 patients with MDD and 40 healthy controls. NEGR1 protein levels were measured by ELISA method. Depressive symptom severity was evaluated by Hamilton Rating-Scale for Depression and Beck Depression Inventory. Results: PBMC from individuals with MDD displayed increased levels of NEGR1 protein in comparison to controls, irrespective of fluoxetine treatment status (p=0.01). Besides, a positive correlation was found between NEGR1 protein levels and Beck scores in fluoxetine treated MDD group (r=0.33, p=0.036). However, no significant relationship was observed in NEGR1 mRNA levels between MDD patients and controls in both fluoxetine treated and non-treated group (p>0.05). Conclusion: NEGR1 protein expression levels may modulate the severity of depressive symptoms in patients with MDD undergoing fluoxetine treatment. Our findings suggest that elevated NEGR1 protein levels in PBMCs may serve as a potential biomarker for MDD, independent of fluoxetine treatment.