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Background: Major depressive disorder (MDD) and anxiety disorders are highly comorbid, sharing many similar symptoms, including impairments in cognitive control. Deficits in cognitive control could be a potential mechanism underlying impaired emotion regulation in mood disorders., Methods: Participants were 44 individuals with no history of mental illness (healthy controls, HC), 31 individuals in the remitted state of MDD (rMDD), and 18 individuals who met lifetime DSM-IV-TR criteria for rMDD and an anxiety disorder in remission (Comorbid). Participants completed a Parametric Go/No-Go (PGNG) test during fMRI. Event-related analyses modeled activity for cognitive control successes (Hits for Targets, Rejections for Lures) and failures (Commissions on Lures) on the PGNG task., Results: The rMDD group showed significantly reduced activity within the cognitive control network (CCN) during Commission errors, including the middle frontal gyrus and inferior parietal lobule (IPL). The Comorbid group showed significantly reduced activity in several clusters within the CCN during correct Rejections, including the left IPL and right inferior frontal gyrus and greater subgenual cingulate. Notably, during correct Rejections, 60% of activation for the Comorbid group was within the Salience and Emotion Network (SEN), with 0% within the CCN., Limitations: The size of the Comorbid subgroup was modest, preventing subanalysis of the different AD subtypes., Conclusions: There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs., (Copyright © 2018. Published by Elsevier B.V.)

Background: Major depressive disorder (MDD) is characterized by dysfunction in cognitive and emotional systems. However, the neural network correlates of cognitive control (cold cognition) and emotion processing (hot cognition) during the remitted state of MDD (rMDD) remain unclear and not fully probed, which has important implications for identifying intermediate phenotypes of depression risk., Methods: 43 young adults with rMDD and 33 healthy controls (HCs) underwent fMRI while completing separate tasks of cold cognition (Parametric Go/No-Go test) and hot cognition (Facial Emotion Processing Test). Two 2 group (rMDD, HC) × 2 event (sad/fearful faces, correct rejections) factorial models of activation were calculated in SPM8. Functional activation was evaluated in the salience and emotional network (SEN) and the cognitive control network (CCN), including hypothesized interaction between group and task within the CCN., Results: Individuals with rMDD demonstrated greater spatial extent of suprathreshold activation within the SEN during sad faces relative to HCs. There were several regions within the CCN in which HCs showed greater activation than rMDD during correct rejections of lures, whereas individuals with rMDD showed greater activation than HCs during sad or fearful faces., Limitations: Results were not directly compared with active MDD., Conclusions: These results provide evidence of deficient CCN engagement during cognitive control in rMDD (dysfunctional cold cognition). Elevated SEN activation during sad faces could represent heightened salience of negative emotional faces in rMDD; elevated CCN activation during emotional faces in rMDD could represent compensatory regulatory control. These group differences may represent vulnerability factors, scars of prior depressive episodes, or processes maintaining wellness., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Sex differences in emotion processing may play a role in women's increased risk for Major Depressive Disorder (MDD). However, studies of sex differences in brain mechanisms involved in emotion processing in MDD (or interactions of sex and diagnosis) are sparse., Methods: We conducted an event-related fMRI study examining the interactive and distinct effects of sex and MDD on neural activity during a facial emotion perception task. To minimize effects of current affective state and cumulative disease burden, we studied participants with remitted MDD (rMDD) who were early in the course of the illness. In total, 88 individuals aged 18-23 participated, including 48 with rMDD (32 female) and 40 healthy controls (HC; 25 female)., Results: fMRI revealed an interaction between sex and diagnosis for sad and neutral facial expressions in the superior frontal gyrus and left middle temporal gyrus. Results also revealed an interaction of sex with diagnosis in the amygdala., Limitations: Data was from two sites, which might increase variability, but it also increases power to examine sex by diagnosis interactions., Conclusions: This study demonstrates the importance of taking sex differences into account when examining potential trait (or scar) mechanisms that could be useful in identifying individuals at-risk for MDD as well as for evaluating potential therapeutic innovations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Studying remitted Major Depressive Disorder (rMDD) facilitates a better understanding of neural mechanisms for risk, given that confounding effects of active symptoms are removed. Disrupted functional connectivity has been reported in multiple networks in MDD. However, no study to date of rMDD has specifically examined connectivity of the ventral striatum (VS), a region highly implicated in reward and motivation. We investigated functional connectivity of the VS in individuals with and without a history of MDD, and in relation to affective personality traits., Methods: Forty-two individuals with rMDD and 28 healthy controls across two sites completed resting-state fMRI and the Behavioral Inhibition System/Behavioral Activation System Scale. Voxel-wise, whole-brain comparisons were conducted across and between groups for four seeds: left and right inferior VS (VSi), left and right superior VS (VSs)., Results: VSs connectivity to temporal and subcortical regions including the putamen and amygdala was positive and greater in HCs compared to rMDD individuals. Across groups, VSi connectivity was positively correlated with trait reward-responsiveness in somatomotor regions. Across groups, VSs connectivity was positively correlated with trait drive, particularly in the putamen, parahippocampal, and inferior temporal gyrus, and was negatively associated with trait behavioral inhibition in the anterior cingulate, frontal gyri, and insula., Limitations: Limitations include scanning at two sites and using multiple comparisons., Discussion: Group connectivity differences emerged from the VSs rather than VSi. VSs showed associations with trait drive and behavioral inhibition, whereas VSi corrrelated with reward-responsiveness. Depression history and affective traits contribute meaningful and specific information about VS connectivity in understanding risk for MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Impaired social cognition, including emotion recognition, may explain dysfunctional emotional and social behaviour in patients with lesions to the ventromedial prefrontal cortex (VMPFC). However, the VMPFC is a large, poorly defined area that can be sub-divided into orbital and medial sectors. We sought to investigate social cognition in patients with discrete, surgically circumscribed prefrontal lesions. Twenty-seven patients between 1 and 12 months post-neurosurgery were divided into groups based on Brodmann areas resected, determined by post-surgical magnetic resonance imaging. We hypothesised that patients with lesions to the VMPFC (n=5), anterior cingulate cortex (n=4), orbitofrontal cortex (n=7) and dorsolateral prefrontal cortex (DLPFC, n=11) would perform worse than a control group of 26 extra-cerebral neurosurgery patients on measures of dynamic facial emotion recognition, theory of mind (ToM) and empathy. Results indicated the VMPFC-lesioned group performed significantly worse than the control group on the facial emotion recognition task overall, and for fear specifically, and performed worse on the ToM measure. The DLPFC group also performed worse on the ToM and empathy measures, but DLPFC lesion location was not a predictor of performance in hierarchical multiple regressions that accounted for other variables, including the reduced estimated verbal IQ in this group. It was concluded that isolated orbital or medial prefrontal lesions are not sufficient to produce impairments in social cognition. This is the first study to demonstrate that it is the combination of lesions to both areas that affect social cognition, irrespective of lesion volume. While group sizes were similar to other comparable studies that included patients with discrete, surgically circumscribed lesions to the prefrontal cortex, future large, multi-site studies are needed to collect larger samples and confirm these results., (Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.)