Genetic variation on the BDNF gene is not associated with differences in white matter tracts in healthy humans measured by tract‐based spatial statistics

The brain‐derived neurotrophic factor (BDNF) is a member of the neurotrophin family and involved in nerve growth and survival. It has also become a major research focus in the investigation of both cognitive and affective processes in the human brain in the last years. Especially, a single nucleotide polymorphism on the BDNF gene called BDNF Val66Met gained a lot of attention, because of its effect on activity‐dependent BDNF secretion and its link to negative emotionality and impaired memory processes. A well‐replicated finding from genetic structural imaging showed that carriers of the less frequent 66Met allele show diminished gray matter volume in several areas of the temporal lobe. New imaging techniques like diffusion tensor imaging now allow investigating the influence of BDNF Val66Met on white matter integrity. We applied tract‐based spatial statistics in a brain image dataset including n = 99 healthy participants. No significant differences between the 66Met and homozygous 66Val carriers were observed when correcting for multiple comparisons. In summary, the BDNF Val66Met polymorphism seems not to play a substantial role with respect to the modulation of the white matter integrity in healthy subjects. Although not in the focus of this study, we also investigated the influence of Eysenck's Personality Questionnaire on the white matter tracts. No significant results could be observed.

[1]  Peter A. Calabresi,et al.  Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification , 2008, NeuroImage.

[2]  Stephen M. Smith,et al.  Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference , 2009, NeuroImage.

[3]  John S. Duncan,et al.  Voxel-based diffusion tensor imaging in patients with mesial temporal lobe epilepsy and hippocampal sclerosis , 2008, NeuroImage.

[4]  Margit Burmeister,et al.  BDNF Val66Met Allele Is Associated with Reduced Hippocampal Volume in Healthy Subjects , 2006, Biological Psychiatry.

[5]  Stephen M. Smith,et al.  A global optimisation method for robust affine registration of brain images , 2001, Medical Image Anal..

[6]  N. Raz,et al.  Human Neuroscience , 2022 .

[7]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[8]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[9]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[10]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[11]  C. Montag,et al.  The BDNF Val66Met polymorphism impacts parahippocampal and amygdala volume in healthy humans: incremental support for a genetic risk factor for depression , 2009, Psychological Medicine.

[12]  Warren D Taylor,et al.  Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter. , 2004, The American journal of psychiatry.

[13]  Dorret I. Boomsma,et al.  Imaging the genetics of brain structure and function , 2008, Biological Psychology.

[14]  Derek K. Jones,et al.  The effect of filter size on VBM analyses of DT-MRI data , 2005, NeuroImage.

[15]  Mervi Eerola,et al.  Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics. , 2010, Journal of affective disorders.

[16]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[17]  H. Kraemer,et al.  Untreated depression and hippocampal volume loss. , 2003, The American journal of psychiatry.

[18]  C. Siao,et al.  Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related Behavior , 2006, Science.

[19]  C. Montag,et al.  An epistasis effect of functional variants on the BDNF and DRD2 genes modulates gray matter volume of the anterior cingulate cortex in healthy humans , 2010, Neuropsychologia.

[20]  J. Groves,et al.  Is it time to reassess the BDNF hypothesis of depression? , 2007, Molecular Psychiatry.

[21]  S. Wakana,et al.  Fiber tract-based atlas of human white matter anatomy. , 2004, Radiology.

[22]  Stephan Züchner,et al.  The brain-derived neurotrophic factor VAL66MET polymorphism and cerebral white matter hyperintensities in late-life depression. , 2008, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[23]  A. Meyer-Lindenberg,et al.  The Brain-derived Neurotrophic Factor Val66met Polymorphism and Variation in Human Cortical Morphology , 2022 .

[24]  Daniel Rueckert,et al.  Nonrigid registration using free-form deformations: application to breast MR images , 1999, IEEE Transactions on Medical Imaging.

[25]  K. Lim,et al.  Diffusion Tensor Imaging in Psychiatric Disorders , 2008, Topics in magnetic resonance imaging : TMRI.

[26]  Paul M. Thompson,et al.  Genetics of microstructure of cerebral white matter using diffusion tensor imaging , 2010, NeuroImage.

[27]  Christian Montag,et al.  The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: Evidence from a genetic imaging study , 2008, NeuroImage.

[28]  Thomas E. Nichols,et al.  Acquisition and voxelwise analysis of multi-subject diffusion data with Tract-Based Spatial Statistics , 2007, Nature Protocols.

[29]  H. Möller,et al.  Hippocampal changes in patients with a first episode of major depression. , 2002, The American journal of psychiatry.

[30]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[31]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[32]  H. Manji,et al.  New insights into BDNF function in depression and anxiety , 2007, Nature Neuroscience.

[33]  C. Montag,et al.  The BDNF Val66Met polymorphism and anxiety: Support for animal knock-in studies from a genetic association study in humans , 2010, Psychiatry Research.

[34]  D. Le Bihan,et al.  Diffusion tensor imaging: Concepts and applications , 2001, Journal of magnetic resonance imaging : JMRI.