ArticleNeuropsychiatric disease and treatment2026
Association Between Tctex1 Domain Containing 1 Expression and Major Depressive Disorder.
Article in Neuropsychiatric disease and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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