Introduction: Exportin-6 (XPO6) regulates nuclear export of actin and related proteins, processes essential for cytoskeletal integrity and synaptic function. Given the importance of these mechanisms in mood regulation, XPO6 dysregulation may contribute to the pathophysiology of major depressive disorder (MDD), yet its role remains largely unknown.
Method: XPO6 mRNA was measured in the peripheral blood of participants with MDD in an acute depressive episode (acute MDD group), MDD in remission, and healthy controls (screened using Chinese health questionnaire-12 and semi-structured interviews to exclude current or past psychiatric disorders) at baseline. XPO6 mRNA levels were measured after 4 weeks of antidepressant treatment in the acute MDD group. The 17-item Hamilton Depression Rating Scale was used to assess depression severity. XPO6 mRNA levels were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR).
Results: We recruited 90 participants in the acute MDD group, 60 in the MDD in remission group, and 70 healthy controls. After adjusting for demographics, a significant difference in baseline XPO6 mRNA levels was found among the three groups (F = 4.34, p = 0.014). In the post hoc analysis, a stepwise pattern in XPO6 mRNA levels was observed (acute MDD group > MDD in remission group > healthy controls). After antidepressant treatment in the acute MDD group, XPO6 mRNA levels significantly decreased (2.23 ± 2.39 vs. 1.82 ± 1.96, p = 0.016).
Conclusion: XPO6 mRNA levels could be a potential biomarker for MDD, which is also associated with depression disease state and treatment response to antidepressants. Larger sample sizes are needed to confirm these results in the future.
Keywords: Biomarkers; Exportin-6; Major depressive disorder.
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