Altered ability to access a clinically relevant control network in patients remitted from major depressive disorder.

Neurobiological models to explain vulnerability of major depressive disorder (MDD) are scarce and previous functional magnetic resonance imaging studies mostly examined "static" functional connectivity (FC). Knowing that FC constantly evolves over time, it becomes important to assess how FC dynamically differs in remitted-MDD patients vulnerable for new depressive episodes. Using a recently developed method to examine dynamic FC, we characterized re-emerging FC states during rest in 51 antidepressant-free MDD patients at high risk of recurrence (≥2 previous episodes), and 35 healthy controls. We examined differences in occurrence, duration, and switching profiles of FC states after neutral and sad mood induction. Remitted MDD patients showed a decreased probability of an FC state (p < 0.005) consisting of an extensive network connecting frontal areas-important for cognitive control-with default mode network, striatum, and salience areas, involved in emotional and self-referential processing. Even when this FC state was observed in patients, it lasted shorter (p < 0.005) and was less likely to switch to a smaller prefrontal-striatum network (p < 0.005). Differences between patients and controls decreased after sad mood induction. Further, the duration of this FC state increased in remitted patients after sad mood induction but not in controls (p < 0.05). Our findings suggest reduced ability of remitted-MDD patients, in neutral mood, to access a clinically relevant control network involved in the interplay between externally and internally oriented attention. When recovering from sad mood, remitted recurrent MDD appears to employ a compensatory mechanism to access this FC state. This study provides a novel neurobiological profile of MDD vulnerability.

Figueroa CA ，Cabral J ，Mocking RJT ，Rapuano KM ，van Hartevelt TJ ，Deco G ，Expert P ，Schene AH ，Kringelbach ML ，Ruhé HG ... -  《-》

The alteration of cognitive function networks in remitted patients with major depressive disorder: an independent component analysis.

Dysfunctional connectivity of resting-state functional networks has been observed in patients with major depressive disorder (MDD), particularly in cognitive function networks including the central executive network (CEN), default mode network (DMN) and salience network (SN). Findings from studies examining how aberrant functional connectivity (FC) changed after antidepressant treatment, however, have been inconsistent. Thus, the purpose of the present study was to explore potential mechanisms of altered cognitive function networks during resting-state between remitted major depressive disorder (rMDD) patients and healthy controls (HCs) and furthermore, the relationship between dysfunctional connectivity patterns in rMDD and clinical symptoms. In this study, 19 HCs and 19 rMDD patients were recruited for resting-state functional magnetic resonance imaging (fMRI) scanning. FC was evaluated with independent component analysis for CEN, DMN and SN. Two sample t tests were conducted to compare differences between rMDD and HCs. A Pearson correlation analysis was also performed to examine the relationship between connectivity of networks and cognitive function scores and clinical symptoms. Compared to healthy controls, remitted patients showed lower connectivity in CEN, mostly in the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior parietal lobule (IPL) and part of the supramarginal gyrus (SMG). Conversely, the bilateral insula, part of the SMG (a key node of the CEN) and dorsal anterior cingulate cortex (dACC) of the DMN showed higher connectivity in rMDD patients. Pearson correlation results demonstrated that connectivity of the right IPL in CEN was positively correlated with cognitive function scores, and connectivity of the left insula was negatively correlated with BDI scores. Though rMDD patients reached the standard of clinal remission, unique impairments of FC in cognitive function networks remained. Aberrant FC between cognitive function networks responsible for executive control was observed in rMDD and may be associated with residual clinical symptoms.

Liu G ，Jiao K ，Zhong Y ，Hao Z ，Wang C ，Xu H ，Teng C ，Song X ，Xiao C ，Fox PT ，Zhang N ，Wang C ... -  《-》

Connectivity patterns of cognitive control network in first episode medication-naive depression and remitted depression.

Cognitive dysfunctions, such as impaired cognitive control, are frequently observed in patients with major depressive disorder (MDD). Although the cognitive control network (CCN) is widely considered a core feature of major depressive disorder (MDD), the relationship between cognitive dysfunction and symptom dimensions remains unclear. This study investigated differences in resting-state functional connectivity of the cognitive control network (CCN) between first-episode medication-naive MDD patients and remitted MDD. We collected resting-state functional MRI (rs-fMRI) data from 22 first-episode medication-naive major depressive disorder (fMDD) patients, 20 patients previously diagnosed with MDD in the remitted phase of depression (rMDD), and 20 healthy controls (HC). The CCN was derived from fMRI images using independent component analysis (ICA), a data-driven image analysis method. Changes in functional connectivity (FC) within the CCN was mainly attenuated in the right dorsolateral prefrontal cortex and the left inferior parietal lobule, while strengthened in the right dorsal anterior cingulate cortex and the right insula in both fMDD and rMDD groups. Compared with the fMDD group, the rMDD group had decreased FC in the bilateral insula and the right dorsolateral prefrontal cortex. Further analysis explored that the FC in the bilateral insula, the right dorsal anterior cingulate cortex and the right inferior parietal lobule were correlated positively cognitive disturbance factor scores in both patients groups. These findings are in agreement with the previous findings that the cognitive control network are impaired in MDD. Furthermore, our results suggest that the alteration of CCN might underpin the cognitive disturbance and the distinct patterns of the CCN between fMDD and rMDD patients may be an important target for effective cognitive remediation in MDD.

Jiao K ，Xu H ，Teng C ，Song X ，Xiao C ，Fox PT ，Zhang N ，Wang C ，Zhong Y ... -  《-》

Striatal Resting-State Connectivity Abnormalities Associated With Different Clinical Stages of Major Depressive Disorder.

Reward deficits and associated striatal circuitry have been implicated in the onset and progression of major depressive disorder (MDD). This work was conducted to clarify how the striatal circuitry is involved in the established risk, acute episodes, and remission of MDD. Striatal subregion resting-state functional connectivity (RSFC) was calculated for 29 currently depressed and 28 remitted patients diagnosed with MDD per the Structured Clinical Interview for DSM-IV, 19 first-degree relatives of these patients, and 57 healthy controls (HCs) based on resting-state fMRI data collected between May 2007 and September 2014. Compared with HCs, the other 3 groups showed increased RSFC between left dorsal caudate (DC) and right insula but reduced RSFC between right putamen and left cerebellum. The currently depressed group showed increased FC between right DC and superior frontal gyrus but reduced RSFC between putamen and right anterior cingulate as well as other striatal nuclei compared with the other 3 groups. Although no results were found in ventral striatum (VS) seeds during analysis of covariance, the comparison between currently depressed and remitted patients showed increased RSFC between right superior VS and left inferior frontal gyrus in currently depressed patients at a more linear threshold. Also, both superior and inferior VS showed increased RSFC with superior and inferior frontal gyri but reduced RSFC with cerebellum in relatives compared with HCs. Higher DC-superior frontal gyrus RSFC (r = 0.438, P = .022) was correlated with more severe depression, but lower within-putamen FC was correlated with more severe depression (r = -0.446, P = .02) and retardation (r = -0.465, P = .011). The findings suggest that reduced VS-frontal, within-putamen, and putamen-cingulate RSFC in currently depressed patients is dependent on current depressive episode and has implications for symptomatic monitoring, while increased caudate-insular and reduced VS-cerebellar RSFC in remitted patients and first-degree relatives might be related to the disease itself and have potential for predicting risk for and recurrence of MDD.

Wang L ，Li F ，Mitchell PB ，Wang CY ，Si TM ... -  《-》

Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression.

Rumination and cognitive reactivity (dysfunctional cognitions after sad mood-induction) remain high in remitted Major Depressive Disorder (MDD) and can contribute to new episodes. These factors have been linked to increased fMRI resting-state functional-connectivity within the Default-Mode Network (DMN). It remains unclear whether (I) increased DMN-connectivity persists during MDD-remission, and (II) whether sad mood-induction differentially affects DMN-connectivity in remitted-MDD vs controls. Moreover, DMN-connectivity studies in remitted-MDD were previously confounded by antidepressant-use. Sixty-two MDD-patients remitted from ≥2 episodes, psychotropic-medication free, and 41 controls, participated in two 5-min neutral and sad mood-inductions by autobiographical-recall and neutral/sad music, each followed by 8-min resting-state fMRI-scanning. We identified DMN-components using Independent Component Analysis and entered subject- and sessions-specific components into a repeated measures analysis of variance. Connectivity-differences were extracted and correlated with baseline cognitive reactivity and rumination as measures of vulnerability for recurrence. After sad vs neutral mood-induction, controls, but not remitted-MDD, showed an increase in connectivity between the posterior-DMN and a cluster consisting mostly of the hippocampus (P = 0.006). Less posterior-DMN-hippocampal connectivity was associated with higher cognitive reactivity (r = -0.21, P = 0.046) and rumination (r = -0.27, P = 0.017). After recalling sad autobiographical-memories, aberrant posterior-DMN-hippocampal connectivity, associated with cognitive reactivity and rumination, remains a neural vulnerability in MDD-remission.

Figueroa CA ，Mocking RJT ，van Wingen G ，Martens S ，Ruhé HG ，Schene AH ... -  《-》