Reduced fractional anisotropy in the uncinate fasciculus in patients with major depression carrying the met-allele of the Val66Met brain-derived neurotrophic factor genotype

Department of Psychiatry, Institute of Neuroscience, University of Dublin, Trinity College Dublin, Dublin, Ireland.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.42). 07/2012; 159B(5):537-48. DOI: 10.1002/ajmg.b.32060
Source: PubMed


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.

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Available from: Alexander Leemans, Sep 15, 2014
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    • "FA is a widely used quantitative measure of white matter microstructure (Basser et al., 1994; Basser and Pierpaoli, 1996) calculated from the diffusion tensor (DTI) model of water diffusion (Thomason and Thompson, 2011). This is an important biomarker in clinical studies, as it can sensitively track the white matter changes in Alzheimer's disease (AD) (Clerx et al., 2012; Teipel et al., 2012), general cognitive function (Penke et al., 2010a; Penke et al., 2010b), and several neurological and psychiatric disorders (Barysheva et al., 2013; Carballedo et al., 2012; Kochunov et al., 2012; Mandl et al., 2013; Sprooten et al., 2011). "
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    • "To our knowledge, this study is the first report on BDNF DNA methylation and brain structural changes in depression. Furthermore , the sample size of our study is relatively large compared to recent DTI studies on the BDNF gene and MDD (Carballedo et al., 2012a; Murphy et al., 2012; Cardoner et al., 2013). Although we believe that our study has multiple strengths as compared to other research, there are several limitations to consider. "
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