PMID- 28387866 OWN - NLM STAT- MEDLINE DCOM- 20190813 LR - 20190813 IS - 1460-2199 (Electronic) IS - 1047-3211 (Print) IS - 1047-3211 (Linking) VI - 28 IP - 5 DP - 2018 May 1 TI - BDNF-Dependent Effects on Amygdala-Cortical Circuitry and Depression Risk in Children and Youth. PG - 1760-1770 LID - 10.1093/cercor/bhx086 [doi] AB - 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. FAU - Wheeler, Anne L AU - Wheeler AL AD - Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8. AD - Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4. FAU - Felsky, Daniel AU - Felsky D AD - Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8. FAU - Viviano, Joseph D AU - Viviano JD AD - Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. FAU - Stojanovski, Sonja AU - Stojanovski S AD - Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4. FAU - Ameis, Stephanie H AU - Ameis SH AD - Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8. AD - Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4. AD - Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. FAU - Szatmari, Peter AU - Szatmari P AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8. AD - Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4. AD - Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. FAU - Lerch, Jason P AU - Lerch JP AD - Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4. AD - Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 1L7. FAU - Chakravarty, M Mallar AU - Chakravarty MM AD - Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada H4H 1R3. AD - Department of Biomedical Engineering, McGill University, 3775 rue University Montreal, Quebec, Canada H3A 2B4. FAU - Voineskos, Aristotle N AU - Voineskos AN AD - Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8. AD - Child Youth and Emerging Adult Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8. LA - eng GR - CIHR/Canada GR - R01 MH099167/MH/NIMH NIH HHS/United States GR - R01 MH102324/MH/NIMH NIH HHS/United States GR - RC2 MH089983/MH/NIMH NIH HHS/United States GR - RC2 MH089924/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cereb Cortex JT - Cerebral cortex (New York, N.Y. : 1991) JID - 9110718 RN - 0 (Brain-Derived Neurotrophic Factor) RN - AE28F7PNPL (Methionine) RN - HG18B9YRS7 (Valine) RN - S88TT14065 (Oxygen) MH - Adolescent MH - Age Factors MH - Amygdala/*diagnostic imaging MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cerebral Cortex/*diagnostic imaging MH - Child MH - Cohort Studies MH - Depression/*diagnostic imaging/*genetics MH - Female MH - Humans MH - Imaging, Three-Dimensional MH - Magnetic Resonance Imaging MH - Male MH - Methionine/genetics MH - Neural Pathways/diagnostic imaging MH - Oxygen/blood MH - Polymorphism, Single Nucleotide/*genetics MH - Psychiatric Status Rating Scales MH - Sex Factors MH - Valine/genetics MH - Young Adult PMC - PMC5907350 EDAT- 2017/04/08 06:00 MHDA- 2019/08/14 06:00 PMCR- 2019/05/01 CRDT- 2017/04/08 06:00 PHST- 2016/10/05 00:00 [received] PHST- 2017/03/24 00:00 [accepted] PHST- 2017/04/08 06:00 [pubmed] PHST- 2019/08/14 06:00 [medline] PHST- 2017/04/08 06:00 [entrez] PHST- 2019/05/01 00:00 [pmc-release] AID - 3106129 [pii] AID - bhx086 [pii] AID - 10.1093/cercor/bhx086 [doi] PST - ppublish SO - Cereb Cortex. 2018 May 1;28(5):1760-1770. doi: 10.1093/cercor/bhx086.