ReviewCognitive impairment in the remitted state of unipolar depressive disorder: A systematic review
Introduction
Cognitive impairment has been widely reported in patients during episodes of major depression e.g. (Burt et al., 1995, Ravnkilde et al., 2002), in the euthymic phase of bipolar disorder e.g. (Quraishi and Frangou, 2002), and in first degree relatives of patients with unipolar e.g. (Christensen et al., 2006) and bipolar disorder e.g. (Bora et al., 2009). In bipolar disorder, attention and executive function seem to be impaired across all phases of the illness, but in respect to learning memory and visuospatial skills, there is little evidence that deficits reflect more than attentional disturbance (Goodwin and Jamison, 2007). Cognitive impairment may not only be a significant factor affecting the individual's ability to function socially and occupationally in everyday life during episodes of illness and in remission (Jaeger et al., 2006), but may have a long term impact on cognition associated with a more deteriorating course of illness than previously assumed.
A number of reviews and meta-analyses have been published on cognitive function in the remitted state of bipolar disorder. Furthermore a number of studies seem to suggest that people suffering from unipolar disorder may also present cognitive dysfunctions during remitted states, but no systematic reviews or meta-analysis has so far been presented on this subject.
The aim of this study was to conduct a systematic review and meta-analysis to evaluate if cognitive function is impaired during the remitted state in patients with unipolar affective disorder compared to healthy control individuals. Our hypothesis was that development of cognitive dysfunction is dependent on the number, duration and severity of previous depressive episodes. Furthermore we aimed to investigate whether the following factors could contribute to the observed findings: 1) age at onset 2) subsyndromal depressive symptoms 3) current-/lifetime treatment with psychoactive medication 4) the time elapsed since the participants suffered the last depressive episode 5) age and gender 6) co-morbid psychiatric disorder and 7) number of episodes requiring hospitalizations. Additionally we aimed to assess the possible sources of bias.
Section snippets
Protocol
Methods of the analysis were specified in advance and documented in a protocol.
Eligibility criteria
We assessed the eligibility of originally reported studies providing data on cognitive function in the remitted state of unipolar depressive disorder compared to control participants as measured in performance on neuropsychological tests.
Strategy of data collection
Studies were identified by searching the MEDLINE-, EMBASE- and PsychInfo databases of original papers published between 1980- November 2009 using the specified search terms: 1) Pub
Study selection and data collection process
Using the above-specified database search strategy, a total of one hundred and eleven articles were identified. Of these eighty two were excluded on the initial screening of abstracts and twenty nine were retrieved for further assessment. By database free keyword search and hand-searches an additional forty one articles of interest were identified. From a total of seventy articles retrieved for further assessment 11 articles were found to meet the criteria for inclusion. Of the fifty seven
Main findings
A total of 11 studies were included in the present review, including a total of 500 patients remitted from unipolar depression and 471 healthy control individuals. In nine of the eleven studies it was found that performance on neuropsychological tests in domains of sustained and selective attention, memory and executive function or in tests providing an estimate on global cognitive function was decreased in patients compared to the healthy control individuals in at least one of the tests used.
Estimation of risk of bias in the included studies
A major source of bias in studies using multiple tests is the possibility of type I error introduced by multiple significance testing and only half of the studies included in this review corrected for multiple testing when relevant.
Very few studies accounted for the selection of participants and controls and the participation rate. Therefore, the results from most of the included studies could be affected by selection bias. In one of the studies the investigator tried to do comparisons between
Conclusions and recommendations for future research
In conclusion, due to limitations in the design of the included studies, the plausibility of the hypotheses explored in this review, are not easily assessed. One of the major drawbacks in the field of research of cognitive function in the remitted state of unipolar affective disorder is that very few studies have employed strict definitions to establish whether patients were fully remitted when neuropsychological testing was performed (see Section 4.2.1). Furthermore, due to the diversity of
Role of funding source
No funding was provided for this study.
Conflict of interest
Lars Vedel Kessing has been a consultant for Bristol-Myers Squibb, Eli Lilly, Lundbeck, AstraZeneca, Pfizer,Wyeth, Servier and Janssen-Cilag. All other authors declare that they have no conflicts of interest.
Acknowledgement
None.
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