Research report
A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder

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Abstract

Background

A number of studies have reported evidence of cognitive deficits in euthymic bipolar patients. Qualitative reviews of the literature have indicated impairments in executive functions and declarative memory are most consistently reported. However, not all primary studies conducted to date have had sufficient power to detect statistically significant differences and there have been few attempts to quantify the magnitude of impairments. This review aims to combine data from available studies to identify the profile of neuropsychological deficits in euthymic bipolar patients and quantify their magnitude.

Method

Systematic literature review and meta-analysis.

Results

Large effect sizes (d  0.8) were noted for aspects of executive function (category fluency, mental manipulation) and verbal learning. Medium effect sizes (0.5  d < 0.8) were found for aspects of immediate and delayed verbal memory, abstraction and set-shifting, sustained attention, response inhibition, and psychomotor speed. Small effect sizes (0.2  d < 0.5) were reported for verbal fluency by letter, immediate memory, and sustained attention.

Limitations

Sufficient data were not available to investigate all domains. For example analyses did not include measures of visuospatial function.

Conclusion

Euthymic bipolar patients demonstrate relatively marked impairment in aspects of executive function and verbal memory. It is not yet clear whether these are two discrete areas of impairment or are related to one another. Future investigations should clarify the functional significance of deficits and indicate whether patients will benefit from ameliorative interventions.

Introduction

Although classically conceptualised as a disorder of mood, a consensus is emerging that patients with bipolar disorder show cognitive deficits both during the acute phase of illness and during remission (Bearden et al., 2001, Quraishi and Frangou, 2002, Savitz et al., 2005). The significance of cognitive deficits in remitted patients is currently not known, but evidence suggests they are negatively related to functional outcome (Atre-Vaidya et al., 1998, Martinez-Aran et al., 2002) and may worsen with increased number of episodes (Denicoff et al., 1999). A profile of deficits has not yet been established as many of the studies in euthymic patients have had low statistical power or have not reported effect sizes. Establishing the magnitude of size effects makes the profile of deficits clearer.

The aim of the present review is to meta-analyse the neuropsychological findings of published studies of euthymic bipolar patients which will aid in both identifying deficits and limiting type II errors from studies with small samples.

Section snippets

Search strategy and study selection criteria

The title and abstract fields of the electronic databases Medline, Embase, Web of Knowledge, and PyschInfo were searched using the following search terms: bipolar disorder or manic depress to identify the relevant illness group, and cognit, attention, learning, memory, executive, or neuropsych to identify relevant studies ( indicates a wildcard). The search was limited to studies in English available between 1980 and August week 1 2005. Inclusion criteria comprised: (1) included an adult

Results

Table 2 and Fig. 1 report the magnitude of the effect sizes computed by the meta-analyses. In all instances (except overall IQ) patients with bipolar disorder performed significantly more poorly than controls (p < 0.004; Table 2). Bipolar patients did not differ significantly from controls in years of formal education received.

The greatest impairment was found in measures of executive function and verbal learning, whereas attention, psychomotor speed and immediate memory were much less affected.

Discussion

These meta-analyses provide strong evidence of cognitive impairments, especially in executive function and verbal learning in bipolar disorder. Large effect sizes were noted for two aspects of executive function (category fluency and mental manipulation) and one of verbal learning. Moderate effect sizes were reported for indices of short and long delay verbal memory, response inhibition, sustained attention, psychomotor speed, abstraction and set-shifting. Small effect sizes were noted for

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