Peripheral BDNF-TrkB Expression and Vitamin D Status in Depression, Prediabetes and Type 2 Diabetes: A Cross-Sectional Biomarker Study.

Background/Objectives: Depression and anxiety cluster with dysglycaemia along a prediabetes-type 2 diabetes continuum, but the signatures of affective and metabolic burden are unclear. We examined whether neurotrophin-related gene expression and 25(OH)D status track symptoms, parameters, or both. Methods: A cross-sectional study of 200 adults (n = 50 each: type 2 diabetes, prediabetes, depressive-anxiety, apparently healthy controls) was conducted. Anthropometry, glycaemic and lipid indices, PHQ-9, GAD-7, serum 25(OH)D and RT-qPCR expression of BDNF, NGF, NTRK1 and NTRK2 in whole peripheral blood were assessed. Multivariable regression, dominance analysis and pre-specified sensitivity analyses were applied. Results: BDNF, NGF and NTRK2 expression progressively decreased from controls to prediabetes and type 2 diabetes and was lowest in the depressive-anxiety group (p < 0.001); NTRK1 expression did not differ. Peripheral BDNF was more closely associated with PHQ-9 and 25(OH)D than with glycaemic or anthropometric indices. Psychiatric variables accounted for approximately 81% of the variance explained by the multivariable model (apparent R2 = 0.257), corresponding to approximately 21% of the total observed variance in log(BDNF). Conclusions: Peripheral BDNF and NTRK2 mRNA and 25(OH)D status were associated with depressive symptom burden more strongly than with metabolic parameters across a prediabetes-type 2 diabetes continuum. These associations describe an exploratory biomarker pattern; they do not establish altered signalling activity, causality or clinical utility, which require prospective validation.