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The psychosocial functioning of individuals suffering from bipolar disorder (BD) has a significant impact on prognosis and quality of life. The aim of this study was to assess brain functional correlates of psychosocial functioning in BD individuals during the performance of a working memory task. Sixty-two subjects (31 euthymic BD individuals and 31 matched healthy controls) underwent structural and functional magnetic resonance imaging scanning while performing the 1- and 2-back versions of the n-back task (1-back and 2-back). The Functional Assessment Short Test (FAST) and its subdomains were used to assess functioning. Whole brain analysis revealed only overall activation differences between BD patients and healthy controls, but the patients showed failure of de-activation in the medial frontal cortex. Six clusters of significant inverse correlation with the FAST scores were found in the dorsolateral prefrontal cortex, the superior parietal cortex, and temporo-occipital regions bilaterally, and in the left inferior frontal cortex. Cognitive and occupational functioning were the subdomains most significantly associated with brain activation in these clusters. The results suggest that poor psychosocial functioning in BD individuals is associated with hypoactivation in a range of cortical regions, including the fronto-parietal working memory network and inferior temporo-occipital regions., Competing Interests: Declaration of competing interest Dr. Vieta has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, and Takeda. Dr. Verdolini has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Otsuka. The other authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: The profiles of cortical abnormalities in schizophrenia and bipolar disorder, and how far they resemble each other, have only been studied to a limited extent. The aim of this study was to identify and compare the changes in cortical morphology associated with these pathologies., Methods: A total of 384 subjects, including 128 patients with schizophrenia, 128 patients with bipolar disorder and 127 sex-age-matched healthy subjects, were examined using cortical surface-based morphology. Four cortical structural measures were studied: cortical volume (CV), cortical thickness (CT), surface area (SA) and gyrification index (GI). Group comparisons for each separate cortical measure were conducted., Results: At a threshold of P = 0.05 corrected, both patient groups showed significant widespread CV and CT reductions in similar areas compared to healthy subjects. However, the changes in schizophrenia were more pronounced. While CV decrease in bipolar disorder was exclusively explained by cortical thinning, in schizophrenia it was driven by changes in CT and partially by SA. Reduced GI was only found in schizophrenia. The direct comparison between both disorders showed significant reductions in all measures in patients with schizophrenia., Conclusions: Cortical volume and cortical thickness deficits are shared between patients with schizophrenia and bipolar disorder, suggesting that both pathologies may be affected by similar environmental and neurodegenerative factors. However, the exclusive alteration in schizophrenia of metrics related to the geometry and curvature of the brain cortical surface (SA, GI) suggests that this group is influenced by additional neurodevelopmental and genetic factors., Competing Interests: Declaration of Competing of Interest All authors declare that they have no conflicts of interest., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: While widespread cortical and subcortical brain functional abnormalities have been found in bipolar disorder, the changes that take place between illness phases and recovery are less clearly documented. Only a small number of longitudinal studies of manic patients, in particular, have been carried out., Methods: Twenty-six bipolar patients underwent fMRI during performance of the n-back working memory task when manic and again after recovery. Twenty-six matched healthy controls were also scanned on two occasions. Task-related activations and de-activations were examined., Results: When manic, the patients showed clusters of significantly reduced activation in the left dorsolateral prefrontal cortex (DLPFC)/precentral cortex and the parietal cortex/superior precuneus bilaterally. They also showed failure of de-activation in the ventromedial frontal cortex (vmPFC). After recovery, activation in the left DLPFC/precentral cortex and in the bilateral parietal cortex/superior precuneus clusters increased significantly. However, failure of de-activation remained present in the vmPFC., Conclusions: Recovery from mania is associated with normalization of DLPFC and parietal hypoactivation, but not with vmPFC failure of de-activation, which accordingly appears to represent a trait abnormality in the disorder., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Neuroimaging studies have revealed evidence of brain functional abnormalities in bipolar depressive disorder (BDD) and major depressive disorder (MDD). However, few studies to date have compared these two mood disorders directly., Methods: Matched groups of 26 BDD type I patients, 26 MDD patients and 26 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the n-back working memory task. A whole-brain ANOVA was used to compare the three groups and clusters of significant difference were examined further using region-of-interest (ROI) analysis., Results: The whole-brain ANOVA revealed a single cluster of significant difference in the medial frontal cortex. The BDD and MDD patients both showed failure to deactivate in this area compared to the controls. The BDD patients showed significantly greater failure of deactivation than the MDD patients, which was not accounted for by differences in severity or chronicity of illness between them., Conclusions: Failure of deactivation, considered to reflect default mode network dysfunction, is present to a greater extent in bipolar than unipolar depression. The study of this network may be useful in the search for brain markers that distinguish the two disorders., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia., Method: A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient-relative-matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them., Results: A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives., Conclusions: Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

Introduction: Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain., Methods: Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task., Results: No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls., Conclusions: Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.

Background: Evidence from decades of magnetic resonance imaging (MRI) research in bipolar disorder has been summarized in meta-analyses of various MRI modalities. Notably, although structural MRI studies suggest gray matter reductions are restricted to specific cortical regions, functional MRI has also shown involvement of subcortical dysfunction. Such disparity in results is open to discussion and requires further exploration with additional MRI modalities., Methods: We applied whole-brain high angular resolution molecular diffusion imaging to compare different properties of the water diffusion process in brain tissues, using different contrasts. Specifically, we looked at fractional anisotropy, mean diffusivity, probability of return to the origin, and generalized fractional anisotropy in a sample of 40 euthymic patients with bipolar disorder and 40 well-matched healthy control subjects., Results: Convergent abnormalities were detected by contrasts in various tissue types. Apart from alterations in white matter (in corpus callosum, cingulum bundle, corona radiata, and superior fronto-occipital fasciculus) and cortical gray matter (in medial frontal cortex, left insula, Heschl's gyrus, and cerebellum), three of the contrasts (fractional anisotropy, mean diffusivity, and generalized fractional anisotropy) revealed abnormalities in subcortical structures, including the hippocampus, the thalamus and the caudate nucleus., Conclusions: Our findings point to a wider pattern of axonal pathology in bipolar disorder than previously thought. Although findings related to cortical gray matter are consistent with structural meta-analyses, subcortical abnormalities suggest a cytoarchitectonic basis for previously reported subcortical dysfunction. Diffusion results could be interpreted in terms of loss of tissue volume and/or altered membrane permeability, agreeing with both hypotheses of mitochondrial malfunction and neuroinflammation., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Background: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated., Method: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups., Results: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network., Limitations: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls., Conclusions: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity., (Copyright © 2012 Elsevier B.V. All rights reserved.)