Major depressive disorder (MDD) is one of the most common psychiatric disorders. Very difficult to treat, this disease is one of the leading causes of suicide. A recent study showed an association between GPR56/ADGRG1 mRNA, MDD and response to antidepressant treatment in blood and in brain. Among GPR56 transcript isoforms, the S4 isoform has recently been associated with microglial synaptic pruning, while microglia are already known as a central player in MDD. Therefore, we hypothesize that S4 is the specific isoform associated with MDD and antidepressant response. To test our hypothesis, an in silico analysis was first performed to identify the different protein and transcript isoforms of GPR56. This analysis was used to design end-point and real-time PCR primers. The presence of all GPR56 isoforms, or specifically the S3 and S4 variants, was assessed by RT-qPCR in leukocytes from a cohort of 46 MDD patients, including responders (n=31) and non-responders (n=17) to antidepressant treatment. We replicated the results of the original study (PMID=32242018), which described an increase in total GPR56 mRNA isoforms in responders. Furthermore, we observed that this variation differed between splice variants, with the S4 variant showing a similar pattern of variation, while the S3 variant showed no significant change. Other variables were considered, such as suicidal behavior (SB), and we showed that S4 is notably sensitive to the SB phenotype compared to S3. These findings confirm our hypothesis that certain GPR56 splice variants may play a more significant role in depression and SB.