Tryptophan hydroxylase-2 polymorphism is associated with white matter integrity in first-episode, medication-naïve major depressive disorder patients

Considerable evidence suggests that the tryptophan hydroxylase-2 (TPH2) gene is associated with the pathophysiology of major depressive disorder (MDD). In the present study, we investigated alterations of white matter (WM) integrity and the impact of TPH2 polymorphism on WM in a sample of 118 first-episode, medication-naïve, MDD patients and 118 well-matched healthy controls. Whole brain analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). The results showed that the MDD group had significantly reduced FA values for the genu and body of the corpus callosum (CC) and the bilateral anterior corona radiate (ACR). In the MDD patient group, the GG homozygote subgroup exhibited a widespread reduction of FA (uncorrected) and significantly reduced FA in the left retrolenticular portion of the internal capsule and left superior longitudinal fasciculus (SLF) compared with those of the T carriers (GT/TT) (FWE corrected). No significant correlation was found between the FA values in any brain region and the patients' clinical variables. Our findings demonstrate the presence of abnormal white matter integrity in untreated patients with first-episode depression. TPH2-rs4570625 polymorphisms may be involved in the pathological mechanism of WM microarchitecture in patients.