Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Anhedonia is a prominent symptom in neuropsychiatric disorders, most markedly in major depressive disorder (MDD) and schizophrenia (SZ). Emerging evidence indicates an overlap in the neural substrates of anhedonia between MDD and SZ, which supported a transdiagnostic approach. Therefore, we used activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging studies in MDD and SZ to examine the neural bases of three subdomains of anhedonia: consummatory anhedonia, anticipatory anhedonia and emotional processing. ALE analysis focused specifically on MDD or SZ was used later to dissociate specific anhedonia-related neurobiological impairments from potential disease general impairments. ALE results revealed that consummatory anhedonia was associated with decreased activation in ventral basal ganglia areas, while anticipatory anhedonia was associated with more substrates in frontal-striatal networks except the ventral striatum, which included the dorsal anterior cingulate, middle frontal gyrus and medial frontal gyrus. MDD and SZ patients showed similar neurobiological impairments in anticipatory and consummatory anhedonia, but differences in the emotional experience task, which may also involve affective/mood general processing. These results support that anhedonia is characterized by alterations in reward processing and relies on frontal-striatal brain circuitry. The transdiagnostic approach is a promising way to reveal the overall neurobiological framework that contributes to anhedonia and could help to improve targeted treatment strategies.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Background: Assertive Community Treatment (ACT) is an evidence-based treatment program for people with severe mental illness developed in high-income countries. We report the first randomized controlled trial of ACT in mainland China.Methods: Sixty outpatients with schizophrenia with severe functional impairments or frequent hospitalizations were randomly assigned to ACT (n= 30) or standard community treatment (n= 30). The severity of symptoms and level of social functioning were assessed at baseline and every 3 months during the 1-year study. The primary outcome was the duration of hospital readmission. Secondary outcomes included a pre-post change in symptom severity, the rates of symptom relapse and gainful employment, social and occupational functioning, and quality of life of family caregivers.Results: Based on a modified intention-to-treat analysis, the outcomes for ACT were significantly better than those of standard community treatment. ACT patients were less likely to be readmitted [3.3% (1/30)v. 25.0% (7/28), Fisher's exact testp= 0.023], had a shorter mean readmission time [2.4 (13.3)v. 30.7 (66.9) days], were less likely to relapse [6.7% (2/30)v. 28.6% (8/28), Fisher's exact testp= 0.038], and had shorter mean time in relapse [3.5 (14.6)v. 34.4 (70.6) days]. The ACT group also had significantly longer times re-employed and greater symptomatic improvement and their caregivers experienced a greater improvement in their quality of life.Conclusion: Our results show that culturally adapted ACT is both feasible and effective for individuals with severe schizophrenia in urban China. Replication studies with larger samples and longer duration of follow up are warranted.