36 The reciprocal relationship between prefrontal cognitive control networks and the default mode network is also perturbed in schizophrenia.37 As with the neuropsychological data, abnormalities in activation of cognitive control networks, deactivation of the default mode network, and interactions between

these two networks are all perturbed in unaffected first-degree relatives of patients with schizophrenia.36,38,39 These impairments Inhibitors,research,lifescience,medical in network activation, connectivity, and interactions may furthermore be related to disruptions in glutamatergic signaling implicated in schizophrenia, specifically through activity at the N-methylD-aspartate (NMDA) receptor. Blockade of the NMDA receptor in healthy subjects using ketamine results in decreased cognitive control network activation, blunted default mode network activation, reductions in the reciprocal connectivity relationship between these regions, and impairment in AZD6244 solubility dmso working memory task performance.40 Inhibitors,research,lifescience,medical Imaging studies of EF in bipolar patients have yielded broadly similar results as observed in schizophrenia. During a working memory task, depressed Inhibitors,research,lifescience,medical bipolar patients fail to activate the DLPFC and deactivate the medial

PFC (mPFC) component of the default mode network.“ In another study of euthymic, manic, and depressed bipolar patients, DLPFC hypoactivation was observed in all patient groups.42 Bipolar patients also show generally similar disruptions in reciprocal connectivity between the default mode network and cognitive control networks as patients with schizophrenia.37 Disruptions in more Inhibitors,research,lifescience,medical anterior lateral prefrontal regions have also been observed during working memory in unaffected first-degree Inhibitors,research,lifescience,medical relatives of bipolar patients.43,44 Depression and anxiety disorders Neuropsychological findings Of the affective disorders, MDD has been best studied with respect to neuropsychological measures of cognition. Indeed, so pervasive

is the presence of EF in MDD, that they are considered a core symptom. Deficits in a range of EFs have been found in MDD with small to large effect sizes, depending on the test or component of EF under investigation.45 In particular, measures of inhibition, sustained attention, working memory, and task shifting are all impacted, suggesting that there is a broad disruption in EF. In a recent large meta-analysis of these studies, the authors failed to ADP ribosylation factor find an effect of current symptoms (ie, symptomatic versus remitted patients) on many aspects of EF task performance,45 suggesting that many of these impairments persist beyond the current mood episode, much as noted in bipolar disorder. Components of EF function are also implicated in anxiety disorders, such as post-traumatic stress disorder (PTSD). Popular models of PTSD center around impairments in the learning and extinction of fear-based memories.