White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms.
This study examined the impact of childhood neglect, serotonin transporter (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms on white matter (WM) integrity in major depressive disorder (MDD) using diffusion tensor imaging (DTI). Fifty-five medication-free MDD patients and 18 controls underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionnaire. Tract based spatial statistics (TBSS) findings revealed reduced fractional anisotropy (FA) in the MDD group in the anterior internal capsule. 5-HTTLPR-S'L' heterozygotes in the MDD group exhibited reduced FA in the internal capsule relative to S'S' and reduced FA in corona radiata compared to L'L'. Probabilistic tractography revealed higher FA in the uncinate fasciculus (UF) for BDNF val/val genotype relative to met-carriers, particularly in individuals with high depression severity. High depression severity and experiences of childhood physical or emotional neglect predicted higher FA in the UF and superior longitudinal fasciculus. Reductions in FA were identified for subgroups of MDD patients who were 5-HTTLPR heterozygotes and BDNF-met carriers. An association between emotional/physical neglect and FA was observed in subjects with high depressive symptoms. Our findings suggest that WM connectivity within frontal and limbic regions are affected by depression and influenced by experiences of neglect and genetic risk factors.
McMaster Integrative Neuroscience Discovery and Study Program, McMaster University, Hamilton, Ontario, Canada.
Erica L
EL
Tatham
Department of Psychiatry, and Clinical Neurosciences, Hotchkiss Brain Institute, Mathison Center for Mental Health Research and Education, University of Calgary, Alberta, Canada.
Rajamannar
R
Ramasubbu
Hotchkiss Brain Institute, University of Calgary, Canada.
Ismael
I
Gaxiola-Valdez
Hotchkiss Brain Institute, University of Calgary, Canada.
Filomeno
F
Cortese
Department of Psychiatry, and Clinical Neurosciences, Hotchkiss Brain Institute, Mathison Center for Mental Health Research and Education, University of Calgary, Alberta, Canada.
Darren
D
Clark
Hotchkiss Brain Institute, University of Calgary, Canada.
Bradley
B
Goodyear
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Jane
J
Foster
McMaster Integrative Neuroscience Discovery and Study Program, McMaster University, Hamilton, Ontario, Canada; Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, Ontario, Canada. Electronic address: hallg@mcmaster.ca.
Geoffrey B
GB
Hall
D000328:Adult; D000069586:Adult Survivors of Child Adverse Events / Q000523:psychology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003863:Depression / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000523:psychology; D056324:Diffusion Tensor Imaging; D004644:Emotions; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human
5-HTTLPR; BDNF; DTI; Depression; Trauma