title: Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder.
abstract: Histological and behavioral research in bipolar disorder (BD) implicates structural abnormalities in the hippocampus. Brain-derived neurotrophic growth factor (BDNF) protein is associated with hippocampal development and plasticity, and in mood disorder pathophysiology. We tested the hypotheses that both the BDNF val66met polymorphism and BD diagnosis are associated with decreased hippocampus volume, and that individuals with BD who carry the met allele have the smallest hippocampus volumes compared to individuals without BD and val/val homozygotes. We further explored localization of morphological differences within hippocampus in BD associated with the met allele. Twenty individuals with BD and 18 healthy comparison (HC) subjects participated in high-resolution magnetic resonance imaging scans from which hippocampus volumes were defined and measured. We used linear mixed model analysis to study effects of diagnosis and BDNF genotype on hippocampus volumes. We then employed three-dimensional mapping to localize areas of change within the hippocampus associated with the BDNF met allele in BD. We found that hippocampus volumes were significantly smaller in BD compared to HC subjects, and presence of the BDNF met allele was associated with smaller hippocampus volume in both diagnostic groups. The BD subgroup who carried the BDNF met allele had the smallest hippocampus volumes, and three-dimensional mapping identified these decreases as most prominent in left anterior hippocampus. These results support effects of BD diagnosis and BDNF genotype on hippocampus structure and suggest a genetic subgroup within BD who may be most vulnerable to deficits in hippocampus and may most benefit from interventions that influence BDNF-mediated signaling.
authors.affiliation: Deparment of Psychiatry, Yale University School of Medicine, New Haven, CT 6511, USA. lara.chepenik@yale.edu
authors.forename: Lara G
authors.initials: LG
authors.lastname: Chepenik
authors.forename: Carolyn
authors.initials: C
authors.lastname: Fredericks
authors.forename: Xenophon
authors.initials: X
authors.lastname: Papademetris
authors.forename: Linda
authors.initials: L
authors.lastname: Spencer
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lacadie
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.forename: James S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Staib
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Blumberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor