METHODOLOGICAL CONSIDERATIONS

Before discussing the nature of cognitive impairment in bipolar disorder, certain methodological issues should be addressed. Unavoidable practical considerations often interfere with ideal methodologies, clouding and weakening conclusions drawn from the results of clinical neuropsychological studies. First, researchers often neglect to indicate whether patients are in a manic, depressed or euthymic phase at the time of neuropsychological assessment. This is in part owing to difficulties with monitoring what are often rapid fluctuations in mood. Second, patients with bipolar disorder are generally receiving a combination of medications - including mood stabilisers, antidepressants, neuroleptics and benzodiazepines - that may or may not influence neuropsychological performance. Differences observed between patients and controls, or patients in different stages of bipolar illness, may be confounded by different medication regimens. Finally, in studies that compare cognitive profiles in mania and depression, differences in the patients' clinical characteristics (such as severity of illness) often make comparisons difficult.

Matching for clinical characteristics within or between patient groups presents a particularly complicated problem for research into this type of illness. Neuropsychological researchers generally attempt to minimise the effects of simpler confounds by controlling as many variables as possible; when choosing control subjects, for example, frequent attempts are made to match patients and controls for age and premorbid intelligence. Matching patients with mania and patients with depression for severity of illness, though, is more difficult, largely because assessment measures differ for each type of illness. The Young Mania Rating Scale and the Hamilton Rating Scale for Depression are often used in mania and depression, respectively, but do not allow comparison across disorders. While some investigators match patients for number of hospitalised episodes, or for some other related factor, the bases of these cross-sectional comparisons are dubious. One method of circumventing some of these problems would be to conduct longitudinal studies of patients with bipolar disorder as they enter different phases of their illness; however, as with between-subject designs, longitudinal within-subject designs cannot ensure that severity levels are equated during manic and depressed phases. In addition, potential benefits come at the price of heightened difficulty, with many researchers unable to manage the resources and lengthy time frame required by this research design.

These methodological problems, among others, make any investigation of disordered mood and cognition almost prohibitively complex, but some measures can be adopted to reduce ambiguities and confounds. For example, because knowing the stage of illness is crucial to an understanding of potential links between mood and cognitive function, this review considers only those studies that specify phase of illness. Although it is much more difficult to resolve questions posed by medication and matching for severity of illness, caution is essential, and in what follows we have attempted to be particularly sensitive to the credibility of results compromised by uncertain methodologies.

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