title: Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology.
abstract: Childhood maltreatment (CM) has been associated with altered brain morphology, which may partly be due to a direct impact on neural growth, e.g. through the brain-derived neurotrophic factor (BDNF) pathway. Findings on CM, BDNF and brain volume are inconsistent and have never accounted for the entire BDNF pathway. We examined the effects of CM, BDNF (genotype, gene expression and protein level) and their interactions on hippocampus, amygdala and anterior cingulate cortex (ACC) morphology. Data were collected from patients with depression and/or an anxiety disorder and healthy subjects within the Netherlands Study of Depression and Anxiety (NESDA) (N = 289). CM was assessed using the Childhood Trauma Interview. BDNF Val66Met genotype, gene expression and serum protein levels were determined in blood and T1 MRI scans were acquired at 3T. Regional brain morphology was assessed using FreeSurfer. Covariate-adjusted linear regression analyses were performed. Amygdala volume was lower in maltreated individuals. This was more pronounced in maltreated met-allele carriers. The expected positive relationship between BDNF gene expression and volume of the amygdala is attenuated in maltreated subjects. Finally, decreased cortical thickness of the ACC was identified in maltreated subjects with the val/val genotype. CM was associated with altered brain morphology, partly in interaction with multiple levels of the BNDF pathway. Our results suggest that CM has different effects on brain morphology in met-carriers and val-homozygotes and that CM may disrupt the neuroprotective effect of BDNF.
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands l.vanvelzen@ggzingeest.nl.
authors.forename: Laura S
authors.initials: LS
authors.lastname: van Velzen
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands.
authors.forename: Lianne
authors.initials: L
authors.lastname: Schmaal
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Department of Neuroscience, University of Groningen, NeuroImaging Center, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Opmeer
authors.affiliation: Institute of Psychology and Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, the Netherlands.
authors.forename: Bernet M
authors.initials: BM
authors.lastname: Elzinga
authors.affiliation: Institute of Psychiatry and Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, the Netherlands.
authors.forename: Nic J A
authors.initials: NJ
authors.lastname: van der Wee
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Department of Psychiatry and Neuroscience Campus Amsterdam, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands.|Department of Psychiatry and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000503:physiopathology; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006179:Gyrus Cinguli / Q000503:physiopathology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D009929:Organ Size / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D001798:Blood Proteins; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; brain structure; brain-derived neurotrophic factor; childhood maltreatment; gene expression