Understanding complex functional wiring patterns in major depressive disorder through brain functional connectome

Abstract

Brain function relies on efficient communications between distinct brain systems. The pathology of major depressive disorder (MDD) damages functional brain networks, resulting in cognitive impairment. Here, we reviewed the associations between brain functional connectome changes and MDD pathogenesis. We also highlighted the utility of brain functional connectome for differentiating MDD from other similar psychiatric disorders, predicting recurrence and suicide attempts in MDD, and evaluating treatment responses. Converging evidence has now linked aberrant brain functional network organization in MDD to the dysregulation of neurotransmitter signaling and neuroplasticity, providing insights into the neurobiological mechanisms of the disease and antidepressant efficacy. Widespread connectome dysfunctions in MDD patients include multiple, large-scale brain networks as well as local disturbances in brain circuits associated with negative and positive valence systems and cognitive functions. Although the clinical utility of the brain functional connectome remains to be realized, recent findings provide further promise that research in this area may lead to improved diagnosis, treatments, and clinical outcomes of MDD.

Functional connectivity of the default mode network subsystems in patients with major depressive episodes with mixed features

“… 24 26 27 These regions are central to emotional regulation and self-reference and executive functions--all areas where deficits have been reported in MDD. 28 Consistent with previous studies, the patients with MDD noMF showed increased functional connectivity in these regions compared with HCs. 29 30 Moreover, patients with MMF displayed higher functional connectivity than the MDD noMF group, indicating MMF might be associated with worse emotional regulation skills.…”

“…The mPFC, PCC and pCunPCC are considered as core hubs of the DMN 24 26 27. These regions are central to emotional regulation and self-reference and executive functions--all areas where deficits have been reported in MDD 28. Consistent with previous studies, the patients with MDD noMF showed increased functional connectivity in these regions compared with HCs 29 30.…”

Graph Theory Analysis of the Cortical Functional Network During Sleep in Patients With Depression

“…This abnormal link strength may be related to excessive brain network activation in patients processing information ( Rotenberg, 2004 ). Multiple studies have pointed out significant increases in the brain connections in patients ( Greicius et al, 2007 ; Goodman et al, 2021 ; Yang et al, 2021 ). In addition, depression is also considered as a “disconnection syndrome” ( Greening et al, 2014 ; Chen et al, 2016 ).…”

Cerebral Venous-Associated Brain Damage May Lead to Anxiety and Depression

“…More importantly, the incidence of CVOD-related anxiety and depression is supposed to get more attention in clinical settings due to the link between anxiety/depression and negative outcomes, such as suicidality [ 16 ]. As indicated in a previous study that the neurobiological factors, neuro-immunological biomarkers, brain-derived neurotrophic factors, and other neuromodulators was found in suicidal behavior, ref.…”

“…As indicated in a previous study that the neurobiological factors, neuro-immunological biomarkers, brain-derived neurotrophic factors, and other neuromodulators was found in suicidal behavior, ref. [ 16 ] the CVOD-induced cerebral damage may not only cause anxiety/depression but also suicidality if the primary symptoms of anxiety/depression were not evaluated early enough.…”