Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder

Abstract

Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states.

Neural correlates of hallucinations in bipolar disorder

“…Despite these limitations, our results are in agreement with those of previous studies, and corroborate earlier findings in the literature. 36 In conclusion, our findings reinforce the view that the salience network may be related to the pathophysiology of psychotic symptoms in BD. Reduced GMV in the right insula may be a candidate trait marker of psychotic features in patients with BD.…”

“…As observed in previous studies, some medications may interfere with the findings of VBM studies in BD. 36,37 Secondly, our sample size limited the interpretation of our results. Third, there was a modest but significant difference in the number of years of formal education reported by each participant group.…”

784. Structural Dysconnectivity of Key Cognitive and Emotional Hubs in Young People at High Genetic Risk for Bipolar Disorder

“…[59][60][61][62][63][64] Likewise, the involvement of the insula adds to a growing number of reports of structural and functional differences in HR cohorts. 23,[65][66][67] The involvement of a left-sided network is unique to the at-risk group (relative to CNs) and is not present in the bipolar group. Although the IFG is involved in a diverse range of tasks, meta-analysis of task functional magnetic resonance imaging suggests that the left (and not the right) IFG shows a selective involvement in empathic responses.…”

Emotional and Motivational Processes in Bipolar Disorder: A Neural Network Perspective

“…Although gray matter reduction in the anterior cingulate cortex appeared to be the most robust finding in bipolar disorder patients [146], the picture is less clear in their relatives as there are both reports of reduced volume [209] and no volumetric alterations [210,211]. Other cortical regions, which were investigated in relatives of bipolar disorder patients, are the medial prefrontal cortex where the volume was found to be reduced [212] and the insula with conflicting results of decreased [212] and increased volume [213,214].…”