Association Between Tctex1 Domain Containing 1 Expression and Major Depressive Disorder.

Abstract

Introduction: Major depressive disorder (MDD) involves peripheral immune-inflammatory dysregulation. Tctex1 Domain Containing 1 (TCTEX1D1), a dynein light chain expressed predominantly in monocytes among circulating immune cells, was recently nominated as a candidate risk gene for MDD by brain-derived transcriptome-wide association studies, but its peripheral mRNA expression in MDD has not been examined. We aimed to quantify TCTEX1D1 mRNA in peripheral blood mononuclear cells (PBMCs) of acute-phase MDD patients and to track its trajectory over four weeks of antidepressant treatment.

Methods: We recruited 154 participants, comprising 89 drug-free patients with acute-phase MDD and 65 healthy controls; 78 patients completed paired four-week antidepressant follow-up. MDD was diagnosed according to DSM-5 criteria, depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAM-D), and treatment response was defined as a ≥50% HAM-D reduction. TCTEX1D1 mRNA in PBMCs was quantified by qRT-PCR. Group differences were tested by analysis of covariance on ΔCt adjusted for age, body mass index (BMI), and sex, with sensitivity analyses for age; longitudinal change was analyzed by linear mixed-effects modeling.

Results: TCTEX1D1 mRNA was significantly lower in MDD patients than in healthy controls (fold-change ratio 0.32, p < 0.001), and the effect persisted across sensitivity analyses for age. No disease × sex interaction was observed (p = 0.568). In female patients, TCTEX1D1 showed only modest diagnostic discrimination (ROC AUC 0.68). Overall TCTEX1D1 levels did not change over four weeks (p = 0.760); an exploratory comparison of responders and non-responders showed only an unconfirmed signal, possibly reflecting regression to the mean.

Conclusion: PBMC TCTEX1D1 mRNA is significantly downregulated in acute-phase MDD. This is the first peripheral-blood evidence for this brain-nominated candidate gene. TCTEX1D1 is best positioned as a disease-state marker rather than a stand-alone diagnostic. Replication in larger cohorts is needed, and the longitudinal findings remain exploratory and hypothesis-generating.