Hasselbalch BJ, Knorr U, Kessing LV. Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. J Affect Disorder 134: 20-31

Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet, Denmark.
Journal of Affective Disorders (Impact Factor: 3.38). 12/2010; 134(1-3):20-31. DOI: 10.1016/j.jad.2010.11.011
Source: PubMed


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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    • "For example, a systematic review of 11 studies involving 500 adult patients in remission from MDD documented persistent deficits in sustained and selective attention, memory, and executive function. However, the heterogeneity across studies did not allow for the estimation of precise effect sizes[37]. In a subsequent study of individuals with unipolar depressive disorder in remission, Hasselbalch et al.[38]reported that the severity of cognitive impairment increases as a function of the cumulative duration of MDEs and, additionally, indicated that the occurrence of psychotic features is associated with worse cognitive performance. Finally, a meta-analysis of 27 studies investigating euthymic adult subjects with MDD showed that executive dysfunction (namely lower inhibitory control) could persist after improvement of depressive symptoms[39]. "
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    ABSTRACT: Background: Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Discussion: Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.
    Full-text · Article · Dec 2016 · BMC Medicine
    • "Cognitive performance in individuals that have recovered from Major Depressive Disorder (MDD) varies considerably between studies. The general tendency is that individuals with a history of depression are moderately impaired on a broad range of cognitive functions, including the domains processing speed, memory, attention , and executive function (Bora et al., 2013; Hasselbalch et al., 2011). A recent meta-analysis suggested that inhibitory control is most strongly affected (Bora et al., 2013). "
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    ABSTRACT: Depression is a common illness which tends to have a relapsing progression. Revealing vulnerability factors is an important step towards improved treatment and prevention. Previous studies of individuals in remission indicate that inhibitory control is more strongly impaired than other cognitive functions. Studies have mostly used Stroop tasks; it is unclear how this population performs on other measures of inhibition. Abnormal reactions to errors may also promote depression relapse, but this has rarely been studied in remitted depression. We used a Stop Signal task and Stroop inhibition task to investigate inhibitory function and post-error reaction time adjustments in 54 individuals with a history of depression and 185 never-depressed controls. Inhibitory processing was slower among the remitted depressed individuals on the Stop Signal task, but no difference was found in Stroop inhibition. The groups were not different on post-error adjustments. This finding extends the understanding of inhibitory deficiency in this population and offers insight into trait markers of depression.
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    • "Although the profile of cognitive dysfunction is similar in these disorders (Etkin et al., 2013), the degree of impairment is more severe in schizophrenia than affective disorders (Barch 2009), and greater in BD than in UD (Gualtieri and Morgan, 2008). In UD, trait-related impairments after clinical remission have small to moderate effect sizes (Bora et al., 2013; Hasselbalch et al., 2011; Rock et al., 2013), indicating that it is partially independent of mood symptoms. These trait-related cognitive deficits have been shown to impede socio-occupational capacity (Jaeger et al., 2006), and increase the risk of depressive relapse (Judd et al., 1998). "
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    ABSTRACT: Background: Persistent cognitive dysfunction in unipolar depression (UD) contributes to socio-occupational impairment, but there are no feasible methods to screen for and monitor cognitive dysfunction in this patient group. The present study investigated the validity of two new instruments to screen for cognitive dysfunction in UD, and their associations with socio-occupational capacity. Method: Participants (n=53) with UD in partial or full remission and healthy control persons (n=103) were assessed with two new screening instruments, the Danish translations of the Screen for Cognitive Impairment in Psychiatry (SCIP-D) and Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and with established neuropsychological and self-assessment measures. Depression symptoms and socio-occupational function were rated with the Hamilton Depression Rating Scale and Functional Assessment Short Test respectively. Results: The SCIP-D and COBRA were valid for detection of objective and subjective cognitive impairment, respectively. The three parallel SCIP-D forms were equivalent. A combined SCIP-D-COBRA measure showed high sensitivity and good specificity for objective cognitive impairment (91% and 70%, respectively). There was no correlation between subjective and objective measures of cognition. Subjective cognitive difficulties correlated more with socio-occupational impairment (r=0.7, p<0.01) than did objective cognitive difficulties, for which there was a weak correlation with the executive skills domain only (r =-0.3, p=0.05). Limitations: A modest sample size. Conclusions: The SCIP-D and COBRA are valid measures of objective and subjective cognitive impairment, respectively, and should ideally be implemented together in the screening for cognitive dysfunction in UD.
    Full-text · Article · Nov 2015 · Journal of Affective Disorders
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