Review
Cognitive impairment in the remitted state of unipolar depressive disorder: A systematic review

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Abstract

Background

It is unclear whether cognitive impairment is prevalent in the remitted state of unipolar disorder.

Aim

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.

Method

Systematic search on existing on-line databases and hand-search of original published papers.

Results

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.

Limitations

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.

Conclusion

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.

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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