title: BDNF-Dependent Effects on Amygdala-Cortical Circuitry and Depression Risk in Children and Youth.
abstract: The brain-derived neurotrophic factor (BDNF) is critical for brain development, and the functional BDNF Val66Met polymorphism is implicated in risk for mood disorders. The objective of this study was to determine how the Val66Met polymorphism influences amygdala-cortical connectivity during neurodevelopment and assess the relevance for mood disorders. Age- and sex-specific effects of the BDNF Val66Met polymorphism on amygdala-cortical connectivity were assessed by examining covariance of amygdala volumes with thickness throughout the cortex in a sample of Caucasian youths ages 8-22 that were part of the Philadelphia Neurodevelopmental Cohort (n = 339). Follow-up analyses assessed corresponding BDNF genotype effects on resting-state functional connectivity (n = 186) and the association between BDNF genotype and major depressive disorder (MDD) (n = 2749). In adolescents, amygdala-cortical covariance was significantly stronger in Met allele carriers compared with Val/Val homozygotes in amygdala-cortical networks implicated in depression; these differences were driven by females. In follow-up analyses, the Met allele was also associated with stronger resting-state functional connectivity in adolescents and increased likelihood of MDD in adolescent females. The BDNF Val66Met polymorphism may confer risk for mood disorders in females through effects on amygdala-cortical connectivity during adolescence, coinciding with a period in the lifespan when onset of depression often occurs, more commonly in females.
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.|Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Daniel
authors.initials: D
authors.lastname: Felsky
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Viviano
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stojanovski
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.|Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Ameis
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.|Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada H4H 1R3.|Department of Biomedical Engineering, McGill University, 3775 rue University Montreal, Quebec, Canada H3A 2B4.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.|Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000679:Amygdala / Q000000981:diagnostic imaging*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D002648:Child; D015331:Cohort Studies; D003863:Depression / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008715:Methionine / Q000235:genetics; D009434:Neural Pathways / Q000000981:diagnostic imaging; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012737:Sex Factors; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D014633:Valine; D010100:Oxygen