Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review.
ABSTRACT It is unclear whether cognitive impairment is prevalent in the remitted state of unipolar disorder.
To evaluate whether cognitive function is impaired in the remitted state in patients with unipolar depression compared with healthy control individuals, and to investigate the association to prior course of illness, i.e. the number, duration and severity of prior depressive episodes.
Systematic search on existing on-line databases and hand-search of original published papers.
A total of 11 studies fulfilled the selection criteria and were included in the review, including a total of 500 patients remitted from unipolar depression and 471 healthy control individuals. In nine of the eleven studies performance on neuropsychological tests was found to be decreased in patients compared to healthy control individuals in at least one of the tests. Methodological drawbacks were prevalent including non-stringent definition of remission and non-correction for multiple testing. Only few studies investigated the association between cognition and prior course of illness and the results were divergent.
Stringent criteria were used in the assessment of eligibility of studies. The studies were first and foremost selected according to the criteria for remission used.
Cognitive dysfunction seems to be present in individuals suffering from unipolar disorder in the remitted state. We recommend that future studies should focus on disentangling the state and trait characteristics of cognitive dysfunction in unipolar disorder and further clarify the associations with clinical phenotype, course of illness and subsyndromal psychopathology. Furthermore, there is a need to identify the cognitive difficulties in individuals suffering from unipolar disorder in relation to psychosocial function, quality of life and risk of recurrence and to assess the effect of treatment intervention on cognitive function.
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ABSTRACT: Major depressive disorder (MDD) is a prevalent and recurring mental disorder often associated with high rates of non-recovery and substantial consequences on psychosocial outcome. Cognitive impairment is one of the most frequent residual symptoms of MDD. The persistence of cognitive impairment even in remitted phases of the disorder, notably in the domains of executive function and attention, suggests that it may serve as a mediational nexus between MDD and poor functional outcome, accounting for occupational and relational difficulties regardless of clinical improvement on depressive symptoms. The critical impact of cognitive deficits on psychosocial dysfunction invites clinicians to regularly screen and assess cognition across multiple domains, taking into account also clinical correlates of cognitive dysfunction in MDD. Despite the availability of several instruments for the screening and assessment of cognitive dysfunction, the lack of consensus guiding the choice of appropriate instruments increases the likelihood to underestimate cognitive dysfunction in MDD in clinical settings. On the other hand, the unsatisfactory effect of most antidepressant treatments on cognitive deficits for many individuals with MDD calls for the development of genuinely novel therapeutic agents with potential to target cognitive dysfunction. Notwithstanding the necessity of further investigations, this review indicates that neuropsychological deficits (e.g., impaired executive functions) are stable markers of MDD and underscores the need for the development of integrative and multi-modal strategies for the prevention and treatment of neuropsychological impairments in MDD.CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). · 2.70 Impact Factor
Canadian journal of psychiatry. Revue canadienne de psychiatrie 12/2014; 59(12):649-54. · 2.41 Impact Factor
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ABSTRACT: Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (eg, enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). · 2.70 Impact Factor