# Association Between GRIN1 rs28489906 and Major Depressive Disorder and Treatment Response to Antidepressants in Patients with Type 2 Diabetes

## TL;DR

The study found that a specific genetic variant in GRIN1 is linked to depression in type 2 diabetes patients and affects antidepressant treatment response.

## Contribution

This is the first study to explore GRIN1's role in depression comorbidity with T2D and its impact on antidepressant response.

## Key findings

- GRIN1 rs28489906 A allele is associated with higher risk of MDD in T2D patients.
- A allele carriers had lower odds of responding to antidepressant treatment.
- Treatment-responsive patients with AG/AA genotypes showed lower HbA1c levels.

## Abstract

What are the main findings?
The A allele of GRIN1 rs28489906 was associated with MDD in T2D.The A allele was associated with decreased odds of treatment response.

The A allele of GRIN1 rs28489906 was associated with MDD in T2D.

The A allele was associated with decreased odds of treatment response.

What are the implications of the main findings?
Potential identification of T2D patients at risk of MDD based on clinical characteristics and GRIN1 genotype.This study contributes to the inclusion of genetics in antidepressant selection.

Potential identification of T2D patients at risk of MDD based on clinical characteristics and GRIN1 genotype.

This study contributes to the inclusion of genetics in antidepressant selection.

Introduction: Major depressive disorder (MDD) is a common comorbidity of type 2 diabetes (T2D) with low rates of treatment response to antidepressants. The pathophysiology of these conditions overlaps in N-methyl-d-aspartate receptors (NMDARs), which are present in neurons and pancreatic cells. GRIN1 encodes NMDARs and has been associated with depression and T2D; however, its role in the coexistence of MDD and T2D and the treatment response to antidepressants has yet to be explored. Objective: We aimed to evaluate the association between GRIN1 rs28489906 and MDD and treatment response to antidepressants in patients with T2D. Methods: A prospective study was conducted on T2D patients enrolled in a comprehensive care program with follow-up at 3 months. Subjects were assessed for MDD, and genotyping for GRIN1 rs28489906 was performed. Depression scores and glycated hemoglobin (HbA1c) were analyzed using the Wilcoxon paired signed-rank test, and a stratified analysis was conducted to assess treatment response. Logistic regression analyses were performed to predict MDD and treatment response. Results: Our sample included 232 patients; among them, 49 (21%) had MDD. Patients with MDD showed a higher frequency of the AA genotype compared with non-MDD subjects (p = 0.026). A allele carriers reported lower treatment response rates (p = 0.049) and decreased odds of treatment response (OR = 0.03, 95% CI 0.002–0.63, p = 0.023). Patients with AG and AA genotypes with treatment response exhibited lower HbA1c (p = 0.029). Conclusions: The A allele of GRIN1 rs28489906 was associated with MDD and treatment response in patients with T2D. Our findings highlight the role of glutamate in these comorbidities and the need for different therapeutic approaches based on genetics.