Depression: higher temporal variability of the functional connectivity of the ventromedial prefrontal cortex and hippocampal system.

It is important to understand the brain differences found in depression in the first episode untreated state, to ensure that differences related to depression and not to the treatments or long-term effects of being depressed are identified. Resting state functional connectivity was measured in 172 patients with not yet treated first-episode major depressive disorder (MDD) with a mean age of 22 years, and 237 healthy controls (HC), using the Human Connectome Project Multimodal Parcellation atlas. Higher temporal variability of resting state functional connectivity was found in depression of ventromedial prefrontal cortex (vmPFC) and medial orbitofrontal cortex regions including 10r, 10v and OFC implicated in reward, and the medial temporal lobe / hippocampal memory system, and for some lateral orbitofrontal cortex regions, in the right hemisphere. These functional differences in depression were found with only two significant differences between the MDD patients and the controls in the volumes of cortical regions, and no significant differences in the weighted streamline numbers between cortical regions measured with diffusion tractography, so functional measures of cortical function are more revealing in this first-episode cohort about brain differences in depression than anatomical differences. The results greatly extend by use of a young first-episode cohort not yet receiving medication our understanding of how a ventromedial prefrontal cortex (vmPFC) reward-related region with major connectivity with orbitofrontal cortex emotion systems and hippocampal memory systems have increased temporal variability and reduced stability in depression, and have implications for treatment, including that this vmPFC reward system should be treated.