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Increasingly, studies have investigated cognitive functioning from the perspective of acute state- to remitted phases of Major Depressive Disorder (MDD). Some cognitive deficits observed in the symptomatic phase persist in remission as traits or scars. The etiological origin and clinical consequences of the neurocognitive profiles reported in the literature are still unclear and may vary across populations. Deficits are suspected to influence the association between MDD and neurodegenerative disorders and could thus be of particular clinical consequence. The aim of this review is to describe the clinical neuropsychological profile in MDD and how it is related to research during the past decade on cognitive deficits in MDD from a state, trait, and scar perspective. This review, with a clinical perspective, investigates research from the past decade regarding cognitive functioning in MDD in a long-term perspective. We focus on the clinical manifestation of deficits, and the potential neurodegenerative consequences of the neurocognitive profile in MDD. Searches in Medline, PsycINFO and Embase were conducted targeting articles published between 2010 and 2020. Examination of the evidence for long-lasting neurocognitive deficits in major depression within the cognitive domains of Memory, Executive Functions, Attention, and Processing Speed was conducted and was interpreted in the context of the State, Scar and Trait hypotheses. Defining the neurocognitive profiles in MDD will have consequences for personalized evaluation and treatment of residual cognitive symptoms, and etiological understanding of mood disorders, and treatments could potentially reduce or delay the development of neurodegenerative disorders.

Major depression (MDD) is associated with cognitive deficits in processing speed and executive function (EF) following first episode (FE). It is unclear whether deficits are state or trait related. Studies following FE MDD over longer periods are lacking, making it uncertain how cognition and symptoms develop after the initial episode. The present study assessed cognitive function and symptoms 5 years following FE MDD. In addition, the study explored relationships between MDD symptoms, rumination, and cognitive deficits with regards to the trait, state, and scar perspective. Twenty-three participants with previous FE MDD, and 20 matched control participants were compared on Delis-Kaplan Executive Function System measures of processing speed and EF, in a 5-year longitudinal follow-up study. Correlations between current symptoms- and history of MDD, rumination, cognition were investigated. Findings indicated that cognitive deficits persisted with no clear signs of exacerbation after initial episode. Inhibition appeared independent of current and previous symptoms of depression. Processing speed was related to depressive- symptoms and rumination. In conclusion, results indicated persisting, stable deficits in both EFs and processing speed. Findings further suggest that depressive symptoms could be related to deficits in processing speed, indicating state effects. There was limited support for worsening of cognition after initial episode. Some aspects of EF like Inhibition could show persistent deficits independent of depressive symptoms indicating trait effects.

Major depressive disorder (MDD) is associated with working memory (WM) impairments. These deficits often persist following remission and are associated with rumination, a recognized risk factor for depression relapse. The efficacy of WM-targeted cognitive remediation as a potential relapse prevention tool has not been investigated. The present pilot study aimed to investigate the feasibility, acceptability, and cognitive benefits of a WM-targeted cognitive remediation program in remitted depression. Twenty-eight MDD participants in remission were recruited. The intervention consisted of twenty-five 30-40-minute training sessions, coupled with weekly coaching, administered over a 5-week period. Before and after the intervention, a battery of objective neuropsychological tests and self-report measures was administered. Key outcomes were WM, inhibition and rumination. Acceptability of the intervention was observed, with 83% showing high motivation, along with WM gains for all completers (n ¼ 18, 64% of recruited participants). The cognitive remediation selectively improved targeted WM functions, as measured by objective tests. This did not translate into self-reported improvements in everyday WM or inhibition. However, all but one completer achieved at least one personal goal related to WM and 44% achieved two or, the maximum possible, three such goals. For remitters whose WM was significantly enhanced after the intervention, the cognitive remediation also decreased dysphoric-mood related rumination. The successful pilot testing of the WM-targeted intervention supports the conduct of a fully powered randomized controlled trial as a relapse prevention approach in remitted MDD.

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Self-reported subjective cognitive difficulties (subjective deficits) and rumination are central residual cognitive symptoms following major depressive disorder (MDD). These are risk factors for more a severe course of illness, and despite the considerable relapse risk of MDD, few interventions target the remitted phase, a high-risk period for developing new episodes. Online distribution of interventions could help close this gap. Computerized working memory training (CWMT) shows promising results, but findings are inconclusive regarding which symptoms improve following this intervention, and its long-term effects. This study reports results from a longitudinal open-label two-year follow-up pilot-study of self-reported cognitive residual symptoms following 25 sessions (40 min), five times a week of a digitally delivered CWMT intervention. Ten of 29 patients remitted from MDD completed two-year follow-up assessment. Significant large improvements in self-reported cognitive functioning on the behavior rating inventory of executive function-adult version appeared after two-years (d = 0.98), but no significant improvements were found in rumination (d < 0.308) measured by the ruminative responses scale. The former showed moderate non-significant associations to improvement in CWMT both post-intervention (r = 0.575) and at two-year follow-up (r = 0.308). Strengths in the study included a comprehensive intervention and long follow-up time. Limitations were small sample and no control group. No significant differences between completers and drop-outs were found, however, attrition effects cannot be ruled out and demand characteristics could influence findings. Results suggested lasting improvements in self-reported cognitive functioning following online CWMT. Controlled studies with larger samples should replicate these promising preliminary findings.

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