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Modulatory effects of brain-derived neurotrophic factor Val66Met polymorphism on prefrontal regions in major
Rebecca MacGregor Legge1, Shahbaz Sendi1, James H Cole1
1Rebecca 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.
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.
Aims:
To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.
Method:
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.
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