Association Analysis of Gene Expression and Brain Image Identifies Gene Signatures in Major Depression Disorder

Abstract

Major depression disorder (MDD) usually comes with structural and functional alterations of the brain, which are determined by altered gene expression patterns. We extracted threefunctional metrics, including Amplitude of Low Frequency Fluctuation, fractional Amplitude of Low Frequency Fluctuation, Regional Homogeneity from fMRI data, and one structural metrics, grey matter density from MRI data, to explore inter-group differences between MDD patients and healthy controls. Based on the association analysis of gene expression and brain imaging, we found 796 gene signatures whose expression was significantly correlated with functional or structural alteration of brain images in MDD. To understand how these genes affect the development of human brains, we used a measure, DPM, to quantitatively estimate the temporal and spatial specificity of MDD-related genes expressed in a region during a period, based on the gene expression dataset of developing human brains from the Allen Brain Atlas. We found MDD-related genes displayed more spatial specificity and less temporal specificity than control genes, suggesting MDD may occur at all periods, but only cause functional and structural changes in specific brain regions. Furthermore, MDD-related genes were found significantly overexpressed in ventrolateral prefrontal cortex, posterior superior temporal cortex, inferior parietal cortex, orbital frontal cortex, primary somatosensory cortex, primary motor cortex, primary auditory cortex, mediodorsal nucleus of the thalamus and cerebellar cortex mainly during adolescence and adulthood, associated with a decrease of grey matter density and a compensatory increase of functional activities affected by MDD. These findings can provide new insights into temporal-spatial expression pattern of MDD-related genes in human brains.