Recent work has also implicated a similar range of cognitive deficits in other disorders that include psychosis. Even when euthymic, Proteasome inhibitor patients with bipolar disorder show cognitive impairments relative to healthy controls with medium to large effect sizes, especially within EF.29 As in schizophrenia, their first-degree relatives also have impairments in EF, albeit with small to medium effect sizes.29 Similarly, cognitive impairments in bipolar disorder correlate with poor functional capacity.30 More

Inhibitors,research,lifescience,medical broadly within the category of affective disorders, patients with Major Depressive Disorder (MDD) who have psychotic symptoms are also cognitively impaired to a similar degree to bipolar patients.31 Neuroimaging findings Consistent

with the neuropsychological literature, Inhibitors,research,lifescience,medical imaging studies of schizophrenia have used a variety of tasks that probe elements of EF with fMRI or positron emission tomography (PET) imaging. A meta-analysis that included all of these studies found that across all of the EF domains Inhibitors,research,lifescience,medical tested, patients consistently hypoactivated a set of largely lateral and medial prefrontal regions.32 Specifically, patients hypoactivated the DLPFC, ventrolateral PFC (VLPFC), dACC, and thalamus (in the region of the mediodorsal nucleus). This is consistent with the failure to engage normal cognitive control circuitry in the prefrontal cortex. Interestingly, greater activation was found in patients in a more posterior region of the dACC, along with a portion of the VLPFC, which may reflect network inefficiency or efforts to compensate Inhibitors,research,lifescience,medical for impaired activation of prefrontal cognitive control regions. In part, however, whether hypoactivation or hyperactivation is observed reflects the difficulty Inhibitors,research,lifescience,medical of the task. DLPFC activity in healthy subjects, for example, decreases from its peak as working memory is stressed beyond its maximal capacity.33 In line with the interpretation that the DLPFC of schizophrenic patients operates less efficiently than that of controls, patients hyperactivate

this region as they strain to keep up at low working memory loads that control subjects can easily handle, and Phosphatidylinositol diacylglycerol-lyase hypoactivate this region at higher working memory loads that exceed patients’ working memorycapacity, but not that of controls.34 The network formulation of EF circuitry outlined above argues that cognitive impairments may arise because of failure to activate prefrontal cognitive control networks, failure to deactivate the default mode network, or abnormalities in the interaction between prefrontal cognitive control networks and the default mode network. In line with this prediction, patients with schizophrenia also display a failure to suppress activity in the default mode network with cognitively engaging tasks.