Experimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fiber tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were analyzed. A significant interaction was found in the UF between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for val-allele and compared to healthy subjects carrying the met-allele. A significant three-way interaction was detected between region of the cingulum (dorsal, rostral, and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers. We provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness.

Previous diffusion tensor imaging (DTI) studies have shown that various factors can affect white matter (WM) tract diffusivity. The aim of the present study was to investigate the effects of childhood adversity (CA), age and gender on WM diffusivity in tracts that are thought to be involved in emotional regulation in individuals with major depressive disorder (MDD) and healthy controls (HC). DTI was obtained from 46 subjects with MDD and 46 HC subjects. Data were pre-processed and deterministic tractography was applied in the cingulum, uncinate fasciculus (UF), fornix, superior longitudinal fasciculus (SLF) and fronto-occipital fasciculus (FOF). In subjects with a history of CA, fractional anisotropy (FA) was greater in the rostral cingulum (RC) and dorsal cingulum, whereas radial diffusivity (RD) was smaller in the RC when compared with subjects with no history of CA. In the UF, FOF and parahippocampal cingulum, FA was greater in the left hemisphere in the subjects with CA when compared with those without CA. Age affected FA, longitudinal diffusivity and RD in the UF, fornix, FOF and SLF, reflecting axonal and myelin degeneration with increasing age. Depression or gender did not have any effects on the diffusivity measures. Due to the cross-sectional nature of the study, a recall bias for CA and possible effects of medical treatment on diffusivity measures could have played a role. CA and age could increase the likelihood to develop WM microstructural anomalies in the brain affective network. Moreover, subjects with CA could be more vulnerable to FA changes.

ObjectiveExperimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain derived neurotrophic factor (BDNF) polymorphism on the white matter fibre tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls.MethodsThirty seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fibre tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus, fornix and cingulum were analysed.ResultsA significant interaction was found in the uncinate fasciculus (UF) between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for valallele and compared to healthy subjects carrying the met-allele. A significant 3-way interaction was detected between region of the cingulum (dorsal, rostral and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers.ConclusionsWe provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness.