Effect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

“…83 A recent DTI study investigating the association between catechol-O-methyltransferase gene polymorphisms and white matter tract integrity in patients with MDD has found that MDD may be associated with the dysfunctional white matter changes in the CC, and the valine homozygote of catechol-O-methyltransferase gene may enhance these pathological changes. 85 Furthermore, studies by Guo and colleagues 66,86 have demonstrated that abnormalities of white matter tracts, mainly in the projection fibres and CC, may contribute to the pathogenesis of treatment-responsive MDD, 66 and that abnormalities of white matter integrity of neuronal tracts connecting 2 brain hemispheres may play a key role in the pathogenesis of TRD. 86 Therefore, decreased FA in the CC observed in our meta-analysis may be diseaserelated and underlie the deficits in emotional modulation and cognitive processing in patients with MDD.…”

“…As for gene regulation, some studies have reported its effects on white matter FA in patients with MDD: an association between the catechol-O-methyltransferase gene Val 158 Met polymorphism and white matter abnormalities 42,85 and a higher remission rate in brain-derived neurotrophic factor (met) carriers than brain-derived neurotrophic factor (val/val) homozygotes. 95 Furthermore, medication-free patients with MDD who have a history of suicide attempts have exhibited significant white matter differences: decreased FA in the left anterior limb of the internal capsule, 22 right lentiform nucleus 22 and white matter adjacent to the right dorsomedial prefrontal cortex 27 in suicide attempters compared with nonattempters.…”

Aging-related magnification of genetic effects on cognitive and brain integrity

“…By contrast, no genetic effects were observed in non-depressed individuals, suggesting that such effects are most easily detected at suboptimal levels of brain integrity, in this case among older persons with mild depression. Relatedly, imaging studies report stronger effects of COMT in populations with reduced brain resources [74][75][76] compared with healthy controls: in patients with major depressive disorder [76] and panic disorder [75], white-matter integrity was lower for Val homozygotes than for Met carriers, whereas no COMT effects were observed for healthy controls. Thus, different study population characteristics may affect whether or not a genetic effect is observed.…”

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive–compulsive disorder

“…While genetic polymorphisms have been associated with WM microstructure in healthy individuals (Braskie et al, , 2013Tost et al, 2013), others have been exclusively associated in patients suffering from different mental disorders (Mounce et al, 2014;Seok et al, 2013). The influence on WM microstructure of the genetic variants associated in the present study had not been previously studied.…”

“…However, genetic markers in genes involved in the dopaminergic (COMT), glutamatergic (GRM3) and neurotrophic (BDNF, NTRK1 and NTRK3) pathways have been recently associated with this WM microstructure measure in healthy subjects and also in patients with schizophrenia or major depression (Braskie et al, , 2013Carballedo et al, 2012;Kohannim et al, 2012;Mounce et al, 2014;Seok et al, 2013;Tost et al, 2013).…”