Effect of BDNF val66met polymorphism on age-related amygdala volume changes in healthy subjects

Brain-derived neurotrophic factor (BDNF) has been implicated in the mechanism of age-related regional brain volumetric changes. Healthy volunteers with the valine to methionine polymorphism at codon 66 of the BDNF gene (val66met) exhibit decreased volume of a number of brain structures, including hippocampus, temporal and occipital lobar gray matter volumes, and a negative correlation between age and the volume of bilateral dorsolateral prefrontal cortices. We sought to characterize the relationship between age, BDNF and amygdala volumes among healthy volunteers. We measured amygdala volumes in 55 healthy, right-handed volunteers who underwent structural magnetic resonance imaging (MRI) and were also characterized demographically and genotyped with respect to BDNF. Using an ANCOVA model, we found that amygdala volumes were inversely correlated with age in BDNF val66met carriers but not in non-carriers. This is the first report of age-related BDNF val66met polymorphism effects on amygdala volume.

[1]  Y. Kawasaki,et al.  Volume reduction of the amygdala in patients with schizophrenia: a magnetic resonance imaging study , 2004, Psychiatry Research: Neuroimaging.

[2]  Kenji Hashimoto,et al.  Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: The possibility to explain ethnic mental traits , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[3]  Alexander Hammers,et al.  Three‐dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe , 2003, Human brain mapping.

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

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

[6]  C. Altar,et al.  Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  Margit Burmeister,et al.  A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression , 2003, Neuropsychopharmacology.

[8]  K. Hashimoto.  BDNF variant linked to anxiety-related behaviors. , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[9]  Paresh D Patel,et al.  Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) Alters the Intracellular Trafficking and Activity-Dependent Secretion of Wild-Type BDNF in Neurosecretory Cells and Cortical Neurons , 2004, The Journal of Neuroscience.

[10]  I. Deary,et al.  The brain-derived neurotrophic factor Val66Met polymorphism is associated with age-related change in reasoning skills , 2006, Molecular Psychiatry.

[11]  Alan C. Evans,et al.  Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. , 2000, Cerebral cortex.

[12]  Takashi Asada,et al.  The Val66Met polymorphism of the brain-derived neurotrophic factor gene affects age-related brain morphology , 2006, Neuroscience Letters.

[13]  Hans-Jürgen Möller,et al.  Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. , 2007, Archives of general psychiatry.

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

[15]  Volkmar Lessmann,et al.  Neurotrophin secretion: current facts and future prospects , 2003, Progress in Neurobiology.

[16]  Michael Davis,et al.  Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Involvement in Amygdala-Dependent Fear Conditioning , 2004, The Journal of Neuroscience.

[17]  Alexander Hammers,et al.  Automatic segmentation of the brain and intracranial cerebrospinal fluid in T1‐weighted volume MRI scans of the head, and its application to serial cerebral and intracranial volumetry , 2003, Magnetic resonance in medicine.

[18]  J. Lieberman,et al.  Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia , 1990, Psychiatry Research: Neuroimaging.

[19]  Jürgen Gallinat,et al.  Association of a functional BDNF polymorphism and anxiety-related personality traits , 2005, Psychopharmacology.

[20]  Oliver T Wolf,et al.  MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation , 1999, Psychiatry Research: Neuroimaging.

[21]  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.

[22]  Xueying Jiang,et al.  BDNF Variation and Mood Disorders: A Novel Functional Promoter Polymorphism and Val66Met are Associated with Anxiety but Have Opposing Effects , 2005, Neuropsychopharmacology.

[23]  Stuart Maudsley,et al.  BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders , 2004, Trends in Neurosciences.

[24]  Ramin V. Parsey,et al.  Acute Occupancy of Brain Serotonin Transporter by Sertraline as Measured by [11C]DASB and Positron Emission Tomography , 2006, Biological Psychiatry.

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

[26]  L. Maffei,et al.  Differential effects of NT‐4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period , 2007, The European journal of neuroscience.

[27]  E. Soriano,et al.  BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization. , 2006, Cerebral cortex.

[28]  T. Wassink,et al.  Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. , 2006, Archives of general psychiatry.

[29]  Michael Davis,et al.  Amygdala BDNF signaling is required for consolidation but not encoding of extinction , 2006, Nature Neuroscience.

[30]  D. G. Herrera,et al.  Sortilin Controls Intracellular Sorting of Brain-Derived Neurotrophic Factor to the Regulated Secretory Pathway , 2005, The Journal of Neuroscience.

[31]  J. Feldon,et al.  Levels of neurotrophic factors in the hippocampus and amygdala correlate with anxiety- and fear-related behaviour in C57BL6 mice , 2006, Journal of Neural Transmission.

[32]  S. Nakanishi,et al.  Expression profile of BDNF-responsive genes during cerebellar granule cell development. , 2006, Biochemical and biophysical research communications.

[33]  J. Virchow,et al.  The impact of age, weight and gender on BDNF levels in human platelets and plasma , 2004, Neurobiology of Aging.

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