Bipolar Disorder, Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism and Brain Morphology

Cheryl Ann Teh,Margaratha Kuchibhatla,Allison Ashley-Koch,Tih-Shih Lee,James Macfall,John Beyer,Ranga Krishnan,Yu-Feng Zang

doi:10.1371/journal.pone.0038469

Cheryl Ann Teh, Margaratha Kuchibhatla + Show 6 more

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https://doi.org/10.1371/journal.pone.0038469

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Abstract

In this study of the effect of bipolar status and presence of BDNF Val66Met polymorphism on differences in regional brain volumes, we hypothesized based on previous studies that 1) bipolar subjects will have smaller regional brain volumes than healthy controls; 2) BDNF Met66 allele carriers within the same population are likely to have smaller regional brain volumes as compared to Val66 homozygyotes. In our Caucasian sample of 166 bipolar subjects and 64 gender-matched healthy controls, we found significant decreases in total (p = 0.005) and regional gray matter volumes in bipolar patients compared to healthy controls, more pronounced in the inferior and posterior parts of the brain, together with a concomitant increase in total CSF (p = 0.012) particularly in the lateral ventricles (p = 0.023). However, there was no difference in white matter volumes noted by other studies. Furthermore we did not find significant differences in other brain regions that have been reported by other authors. Nor did we find a significant effect of BDNF on these measurements.

Highlights

Bipolar disorder is a significant psychiatric condition that affects approximately 1–3% of the population [1]
Various neuroanatomical changes have been observed in structural Magnetic Resonance Imaging (MRI) studies of bipolar patients compared to healthy subjects, most notably, increased ventricular volumes [4] with corresponding regional grey matter reductions in various subcortical structures implicated in emotional processing, including the anterior cingulate and insula cortex [5], amygdala [6] and hippocampus [7]
Some studies [8,21] have found that the Val allele is over transmitted in bipolar disorder, a pattern found in schizophrenia, while others [9] have reported no association between variation at the Brain-Derived Neurotrophic Factor (BDNF) Val66Met locus and susceptibility to bipolar disorder

Summary

Introduction

Bipolar disorder is a significant psychiatric condition that affects approximately 1–3% of the population [1] The pathophysiology of this disease remains poorly understood, though a dysregulation of the anterior limbic network is thought to be involved. A valine(G) to methionine (A) substitution in the 59 proregion, on nucleotide 196, codon 66, produces the SNP This polymorphism appears to confer genetic susceptibility to a range of psychiatric disorders including anxiety disorders [15,16] schizophrenia [17] and of particular relevance to this paper, mood disorders – both unipolar depression, in particular late life depression [18,19,20], and bipolar disorder [8,21,22]. Some studies [8,21] have found that the Val allele is over transmitted in bipolar disorder, a pattern found in schizophrenia, while others [9] have reported no association between variation at the BDNF Val66Met locus and susceptibility to bipolar disorder

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