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Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State.

ABSTRACT: Introduction: Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Materials and Methods: Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Results: Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further post-hoc t-tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Conclusions: Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.

SUBMITTER: Zeng C

PROVIDER: S-EPMC8032940 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IMPORTANCE:Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE:To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS:A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES:Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS:Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R?=?-.523, P?=?.01), dysphoria (R?=?-.455, P?=?.05), and lassitude (R?=?-.449, P?=?.05) and was positively correlated with well-being (R?=?.470, P?=?.03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE:Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

Project description:BackgroundBipolar disorder (BD) is a mental disorder characterized by mood fluctuations between an acute episodic state of either mania or depression and a clinically remitted state. Dysfunction of large-scale intrinsic brain networks has been demonstrated in this disorder, but it remains unknown whether those network alterations are related to different states.MethodsIn the present study, we performed a meta-analysis of whole-brain seed-based resting-state functional connectivity (rsFC) studies in BD patients to compare the intrinsic function of brain networks between episodic and remitted states. Thirty-nine seed-based voxel-wise rsFC datasets from thirty publications (1047 BD patients vs 1081 controls) were included in the meta-analysis. Seeds were categorized into networks by their locations within a priori functional networks. Seed-based d mapping analysis of between-state effects identified brain systems in which different states were associated with increased connectivity or decreased connectivity within and between each seed network.FindingsWe found that BD patients presented decreased connectivity within the affective network (AN) in acute episodes but not in the remitted state of the illness. Similar decreased connectivity within the default-mode network (DMN) was also found in the acute state, but it was replaced by increased connectivity in the remitted state. In addition, different patterns of between-network dysconnectivity were observed between the acute and remitted states.InterpretationThis study is the first to identify different patterns of intrinsic function in large-scale brain networks between the acute and remitted states of BD through meta-analysis. The findings suggest that a shift in network function between the acute and remitted states may be related to distinct emotional and cognitive dysfunctions in BD, which may have important implications for identifying clinically relevant biomarkers to guide alternative treatment strategies for BD patients during active episodes or remission.FundingThis study was supported by grants from the National Natural Science Foundation of China (81171488, 81671669 and 81820108018) and by a Sichuan Provincial Youth Grant (2017JQ0001).

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Abnormal Large-Scale Network Activation Present in Bipolar Mania and Bipolar Depression Under Resting State.

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