title: Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow.
abstract: Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling.
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Shau-Ming
authors.initials: SM
authors.lastname: Wei
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Eisenberg
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Nabel
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Kohn
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: J Shane
authors.initials: JS
authors.lastname: Kippenhan
authors.affiliation: Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Dwight
authors.initials: D
authors.lastname: Dickinson
authors.affiliation: Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kolachana
authors.affiliation: Section on Integrative Neuroimaging.|Clinical and Translational Neuroscience Branch, NIMH IRP, NIH, Bethesda, MD, USA.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Berman
mesh_terms: D000293:Adolescent; D000328:Adult; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002560:Cerebrovascular Circulation / Q000235:genetics / Q000502:physiology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010551:Personality / Q000235:genetics* / Q000502:physiology*; D010556:Personality Tests; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D012146:Rest; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF genotype; PET; frontolimbic circuitry; harm avoidance; resting rCBF