The neuroprogressive nature of major depressive disorder: evidence from an intrinsic connectome analysis

Abstract

Major depressive disorder (MDD) is a prevailing chronic mental disorder with lifetime recurring episodes. Recurrent depression (RD) has been reported to be associated with greater severity of depression, higher relapse rate and prominent functioning impairments than first-episode depression (FED), suggesting the progressive nature of depression. However, there is still little evidence regarding brain functional connectome. In this study, 95 medication-free MDD patients (35 with FED and 60 with RD) and 111 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scanning. After six months of treatment with paroxetine, 56 patients achieved clinical remission and finished their second scan. Network-based statistics analysis was used to explore the changes in functional connectivity. The results revealed that, compared with HCs, patients with FED exhibited hypoconnectivity in the somatomotor, default mode and dorsal attention networks, and RD exhibited hyperconnectivity in the somatomotor, salience, executive control, default mode and dorsal attention networks, as well as within and between salience and executive control networks. Moreover, the disrupted components in patients with current MDD did not change significantly when the patients achieved remission after treatment, and sub-hyperconnectivity and sub-hypoconnectivity were still found in those with remitted RD. Additionally, the hypoconnectivity in FED and hyperconnectivity in RD were associated with the number of episodes and total illness duration. This study provides initial evidence supporting that impairment of intrinsic functional connectivity across the course of depression is a progressive process.

Altered functional connectivity in first-episode and recurrent depression: A resting-state functional magnetic resonance imaging study

“…Previous studies have found reduced FC in the DMN, dorsal attention network, and somatomotor network in the FDE group compared with the recurrent depression (RD) group, suggesting possible FC hypoconnectivity in multiple brain networks in the FDE group ( 34 ). In this study, we used a seed-based FC approach to systematically compare FC abnormalities in the DMN, CCN, and AN in RDE patients, FDE patients, and HCs.…”

“…MDD has also been studied previously using a combination of several networks, including adolescent depression or TRD ( 23 , 30 – 34 ). Most studies have focused on FC abnormalities in the DMN, CCN, and AN in MDD patients ( 29 , 30 , 32 – 34 ).…”

“…MDD has also been studied previously using a combination of several networks, including adolescent depression or TRD ( 23 , 30 – 34 ). Most studies have focused on FC abnormalities in the DMN, CCN, and AN in MDD patients ( 29 , 30 , 32 – 34 ). The functions of emotional, cognitive, behavioral, and transdiagnostic positive and negative valence systems in depressed patients are closely related to the three networks (DMN, CCN, and AN) ( 29 , 35 , 36 ).…”

Proton magnetic resonance spectroscopy of N-acetyl aspartate in first depressive episode and chronic major depressive disorder: a systematic review and meta-analysis

“…We hypothesize that cerebral NAA concentrations should be lower in MDD patients relative to HC. Our hypothesis is that NAA reduction will be larger in cMDD as compared to FED, in accordance with progressive neuronal damage or hypometabolic changes over the course of the illness(3).…”

“…In MDD, a malfunction of multiple brain areas, including the limbic system and the prefrontal cortex, has been postulated, but, despite significant advances, its pathophysiology and the molecular basis of treatments are still poorly understood. This is further complicated by the heterogeneity of disease phases, as clinical(2) and radiological(3) markers differ between First Episode of Depression (FED) and chronic MDD (cMDD). Differentiating MDD stages has important implications for patient care and clinical research(4).…”