FK506 Binding Protein 5 and Solute Carrier Family 6 Member 4 Genes as Biomarkers and Treatment Responders in Major Depressive Disorder: Randomized Clinical Trial

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Background: Major depressive disorder is one of the most common causes of disability in people of the world, so it has imposed a heavy burden on society in terms of medicine and the economy. One of the important and valuable biomarkers in identifying major depressive disorder is the FKBP5 and SLC6A4 genes in depressed patients. Objectives: This study aimed to evaluate the sensitivity and specificity of FKBP5 and SLC6A4 genetic markers in distinguishing major depressive disorder (MDD) patients from healthy controls (HCs) and the responses to cognitive behavioral therapy (CBT) and fluoxetine therapy. Methods: Forty patients diagnosed with MDD based on the diagnostic and statistical manual of mental disorders, fifth edition (DSM-V) criteria and 44 HCs were included in our study from patients of private clinics and Zare Hospital Sari from January 2022 to March 2022. Sampling was carried out from MDD patients and HCs. The patients were randomly assigned to CBT or fluoxetine therapy groups using a randomization block method. The CBT group (12 weeks/one session per week/90 minutes per session), the fluoxetine therapy group (3 months/20 mg daily/weekly follow-up), and relative gene expression alterations were calculated using the quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique. Results: The receiver operating characteristic (ROC) curve analysis showed that FKBP5 [area under the curve (AUC) = 0.724, standard error = 0.054, P < 0.001] and SLC6A4 (AUC = 0.661, standard error = 0.092, P = 0.036) genes have acceptable sensitivity and accuracy in identifying MDD from HCs. After the therapeutic intervention, a significant decrease in the Beck Depression Inventory-II (BDI-II) scores was observed in both groups (CBT group, P < 0.001, fluoxetine group, P < 0.001). Comparing before and after treatment in the CBT group, a significant decrease in FKBP5 (P < 0.001) and SLC6A4 (P < 0.001) gene expression were observed. In the fluoxetine group, SLC6A4 (P = 0.44) gene expression did not show any significant changes, but FKBP5 (P < 0.001) gene expression decreased. Conclusions: The present study showed that the FKBP5 and SLC6A4 genes are appropriate biomarkers for distinguishing MDD patients from HCs and treatment response. However, more research is required to identify biomarkers in distinguishing MDD patients from HCs and treatment response.