Biomarkers for Adolescent MDD from Anatomical Connectivity and Network Topology Using Diffusion MRI

Due to the high resistance (35%) to the current treatment methods in adolescent Major Depressive Disorder (MDD) and its tragic outcomes, the discovery of treatmentrelated responders is critical to developing effective treatments. In this paper, the permutation test is performed to identify statistically significant changes in anatomical characteristics during pairwise comparisons among the control group (n=27), treated MDD group (n=37), and untreated MDD group (n=15). The anatomical characteristics include: 1) anatomical connectivity defined using DTI metrics between a pair of brain regions, and 2) topological measurements of anatomical networks. With the Bonferroni correction for multiple-comparison, significant alterations in community structure and local topology were identified as the p-value < 5%, which include: 1) a reduced nodal centrality (degree and strength) on right hippocampus for treated compared to untreated group, 2) an elevated clustering coefficient and local efficiency on right lateral orbitofrontal cortex for untreated compared to the combination of control and treated groups, 3) an increased participation coefficient for untreated patients on left insula cortex in the meandiffusivity network compared to the combination of control and treated groups, and 4) a degraded module degree z-score on right caudate nucleus for all the patients compared to the control group. Two connections, hippocampus-insula in the right hemisphere and parahippocampal-insula in the left hemisphere, were found significantly altered in TR, AD, and FA due to MDD.