The purpose of the present, article is to summarize psychological

and ncurobiological studies that, have sought, to characterize the profile of brain dysfunction in bipolar disorder. In the first, part of the review, we will examine the evidence from studies of neurocognition in bipolar disorder. Neuropsychological testing with standardized assessment, procedures can provide indirect, measures of activity in brain systems, based on validatory research from neuroimaging, studies of human lesion Inhibitors,research,lifescience,medical patients, and translational data from nonhuman species.4 Although the index of underlying brain function is indirect, the advantage of this approach is that neuropsychological testing is relatively inexpensive, and can be readily administered in a clinical or hospital setting. In the second part of the review, we will examine studies Inhibitors,research,lifescience,medical that have used brain imaging techniques, chiefly functional magnetic resonance imaging (fMRI),to directly quantify the neural abnormalities AC220 mouse associated with bipolar disorder. Investigation of the profile of brain changes in bipolar disorder has been hampered by a number of factors. First, it has become apparent that, Inhibitors,research,lifescience,medical in bipolar disorder, there is a combination of both state-related changes during illness episodes, and more enduring trait-related changes which persist, through periods of symptom remission.5 This accumulating

evidence for trait deficits Inhibitors,research,lifescience,medical in bipolar disorder contrasts with the original Kraepelinian concept, of bipolar disorder, which highlighted the apparent recovery of function between episodes (in contrast to the chronic deteriorating course of schizophrenia dementia praecox). Of course, the identification of trait markers for bipolar disorder raises the possibility that neurocognitive variables may represent illness endophenotypes, related to underlying genetic liability.6

Inhibitors,research,lifescience,medical A second complication pertains to the state-related changes: whilst, the manic and depressive states of bipolar disorder have some neuropsychological similarities, they also have some important differences. For example, the florid disinhibition and risk-taking during mania are highly reminiscent, of the effects of brain lesions to the orbitofrontal cortex, as we will discuss further below. A related third point, is that, multiple domains these of cognitive function are clearly disrupted in bipolar disorder, including attention, executive function, emotional processing, and memory,7-8 and these cognitive domains may be differentially affected by state and trait variables. Finally, the current, literature on bipolar disorder has failed to consistently control for a range of clinical factors that may putatively impact, on neurocognition, including medication status,9 comorbidities including substance use disorders,10 and specific symptom dimensions such as suicidally11 or insomnia.