PPARγ as a predictive biomarker for antidepressant response in major depressive disorder: Insights from TNIP1 transcriptional regulation

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Major depressive disorder (MDD) is a debilitating disease possibly linked to immune defense mechanisms. TNIP1, a key anti-inflammatory regulator in NF-κB and TLR pathways, is implicated in MDD, but its transcriptional regulation and role in treatment response are unclear. We analyzed mRNA expression of TNIP1 and 13 transcription factors in monocytes from pre- and post-treatment (4-6 weeks) MDD patients and healthy controls. Peripheral blood mononuclear cells were isolated, tagged by CD14, and mRNA was extracted and analyzed. Participants were recruited at Kaohsiung Chang Gung Memorial Hospital (2014–2025). ANCOVA, paired t-tests, and multiple linear regression adjusted for age, gender, BMI, and smoking were used to compare groups and predict treatment outcomes. This study encompassed 62 MDD patients and 52 healthy controls. Pre-treatment HAMD-17 averaged 23.90 ± 4.60, and post-treatment HAMD-17 averaged 8.43 ± 4.24. MDD patients showed higher PPAR-γ (p < 0.001), FOS (p = 0.023), and lower JUN (p = 0.029) expression than controls. Post-treatment, TNIP1 expression increased (p = 0.031). Lower pre-treatment PPAR-γ predicted greater symptom improvement (p = 0.016). This study highlights the differential expression of PPAR-γ, FOS, and JUN in MDD patients, underscoring their potential roles in immune regulation. The association between lower pre-treatment PPAR-γ expression and improved treatment outcomes suggests its utility as a biomarker for predicting therapeutic response. • Lower pre-treatment PPARγ mRNA in monocytes predicts greater improvement in MDD depressive symptoms, indicating its potential as a biomarker. • MDD patients show significantly higher PPARγ and FOS, and lower JUN mRNA expression compared to healthy controls, reflecting inflammatory mechanisms. • TNIP1 mRNA expression significantly increases in MDD patients’ monocytes after 4–6 weeks of antidepressant treatment.

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