Modulatory effects of brain-derived neurotrophic factor Val66Met polymorphism on prefrontal regions in major depressive disorder.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD.


OBJECTIVE
To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.


METHODS
Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction.


RESULTS
People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area.


CONCLUSIONS
Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Rebecca MacGregor
RM
Legge
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Shahbaz
S
Sendi
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
James H
JH
Cole
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Sarah
S
Cohen-Woods
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Sergi G
SG
Costafreda
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Andrew
A
Simmons
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Anne E
AE
Farmer
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Katherine J
KJ
Aitchison
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Peter
P
McGuffin
Rebecca MacGregor Legge, MSc, Shahbaz Sendi, MD, Department of Psychological Medicine, Institute of Psychiatry, King's College London; James H. Cole, PhD, Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, UK; Sarah Cohen-Woods, PhD, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia; Sergi G. Costafreda, MD, PhD, Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Andrew Simmons, PhD, Department of Neuroimaging, Institute of Psychiatry, National Institute of Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, King's College London; Anne E. Farmer, MD, FRCPsych, Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, UK; Katherine J. Aitchison, PhD, MRCPsych, Department of Psychiatry, University of Alberta, Edmonton, Canada; Peter McGuffin, PhD, FMedSci, NIHR Biomedical Research Centre for Mental Health at South London and Department of Old Age Psychiatry, Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London; Cynthia H.Y. Fu, MD, PhD, Department of Psychological Medicine, Institute of Psychiatry, King's College London, and School of Psychology, University of East London, London, UK.
Cynthia H Y
CH
Fu
D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human