A detailed description of this cognitive and neurobiological profile has been elusive, due to a combination of both state-and trait-related changes in bipolar disorder. In principle, three distinct profiles may exist. An abnormality may be a state-related deficit that recovers fully during periods of remission, but

is similarly affected by both manic and depressive episodes. We have presented evidence that executive dysfunction may adhere to this profile, associated with reduced neural activation in the dorsal and lateral aspects of the prefrontal cortex. However, it should be noted that executive #AZD6244 keyword# dysfunction in bipolar disorder is heterogeneous, and this deficit, can persist in some patients, probably as a function of clinical features such as illness severity and possibly medication status. The second profile of deficit, is the trait marker: an impairment that is present during acute episodes but, which also persists during periods of remission. There is reasonable

evidence Inhibitors,research,lifescience,medical that deficits in target detection on sustained attention (CPT) tasks adhere to a trait profile. Trait deficits may occur as a consequence Inhibitors,research,lifescience,medical of repeated illness episodes (as may be the case for executive dysfunction), or may predate the onset, of the illness and be associated with genetic liability Inhibitors,research,lifescience,medical to bipolar disorder. Ongoing research in high-risk populations, such as the unaffected first-degree relatives of bipolar probands, may identify neurocognitive markers

associated with bipolar vulnerability, but studies so far have been inconclusive and limited by small sample sizes.107-109 The third profile is of a state-related marker that is restricted to either the manic or the depressive episodes. We have presented some evidence that deficits in risk assessment, emotional decision-making, and impulsive responding Inhibitors,research,lifescience,medical are pronounced during the manic episodes, and these may represent objective, quantifiable indicators of the classic manic symptoms of disinhibition and behavior with harmful consequences (eg, spending sprees and sexual indiscretions). It is likely that, these deficits are linked to dysregulation Calpain of the orbitofrontal cortex. The degree to which these changes are restricted to mania is equivocal currently, given the lack of data in bipolar depression. Functional imaging studies in bipolar depression have indicated a hyperreactivity of subcortical limbic systems, such that emotionally neutral material may be processed in an emotional manner. Whilst, it is promising that this phenomenon may show specificity to bipolar disorder compared with major depressive disorder,87 it is not, yet fully clear whether this effect, is restricted to bipolar depression or could represent, a trait marker.