Childhood Stress, Serotonin Transporter Gene and Brain Structures in Major Depression
Résumé
Abstract The underlying neurobiology of major depression is likely to represent an interaction between genetic susceptibility and environmental factors like stress. We investigated in a multimodal high-resolution MRI-genetic study whether reduced hippocampal volumes and other brain alterations are associated with the tri-allelic polymorphism of the serotonin transporter and childhood stress in patients with major depression and healthy subjects. Patients with MD and healthy participants were investigated using high-resolution magnetic resonance imaging (MRI) and genotyping for serotonin transporter polymorphism in the promoter region of the serotonin transporter gene (SLC6A4, 5-HTTLPR). Region of interest analysis of the hippocampus, whole brain voxel-based morphometry (VBM) and assessment of childhood stress were carried out. Patients carrying the risk s-allele developed smaller hippocampal volumes when they had a history of emotional neglect compared to patients who only had one risk factor (environmental or genetic). In patients childhood stress also independently from the genotype predicted further hippocampal white matter alterations. Moreover, the left prefrontal cortex was smaller in patients, whereby childhood stress resulted in larger prefrontal volumes in those subjects carrying the non-risk L-allele suggesting preventive effects. The findings indicate that subjects with both environmental and genetic risk factors are susceptible to stress-related hippocampal changes. Structural brain changes due to stress represent part of the mechanism by which the illness risk and outcome might be genetically mediated.
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