Structural covariance network of the hippocampus–amygdala complex in medication-naïve patients with first-episode major depressive disorder

Abstract Background The hippocampus and amygdala are densely interconnected structures that work together in multiple affective and cognitive processes that are important to the etiology of major depressive disorder (MDD). Each of these structures consists of several heterogeneous subfields. We aim to explore the topologic properties of the volume-based intrinsic network within the hippocampus–amygdala complex in medication-naïve patients with first-episode MDD. Methods High-resolution T1-weighted magnetic resonance imaging scans were acquired from 123 first-episode, medication-naïve, and noncomorbid MDD patients and 81 age-, sex-, and education level-matched healthy control participants (HCs). The structural covariance network (SCN) was constructed for each group using the volumes of the hippocampal subfields and amygdala subregions; the weights of the edges were defined by the partial correlation coefficients between each pair of subfields/subregions, controlled for age, sex, education level, and intracranial volume. The global and nodal graph metrics were calculated and compared between groups. Results Compared with HCs, the SCN within the hippocampus–amygdala complex in patients with MDD showed a shortened mean characteristic path length, reduced modularity, and reduced small-worldness index. At the nodal level, the left hippocampal tail showed increased measures of centrality, segregation, and integration, while nodes in the left amygdala showed decreased measures of centrality, segregation, and integration in patients with MDD compared with HCs. Conclusion Our results provide the first evidence of atypical topologic characteristics within the hippocampus–amygdala complex in patients with MDD using structure network analysis. It provides more delineate mechanism of those two structures that underlying neuropathologic process in MDD.