Dynamic functional hippocampal markers of residual depressive symptoms in euthymic bipolar disorder

Abstract

Objectives : Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. Methods : We assessed hippocampus‐based dFC coactivation patterns (CAPs) on resting‐state fMRI data of 25 euthymic BD patients and 25 age‐ and sex‐matched healthy controls (HC). Results : Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo‐insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default‐like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. Conclusions : Overall, we observed alterations of large‐scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self‐centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow‐up of BD patients and of disabling residual depressive symptoms in particular.

Manic Residual Symptoms Also Deserve Attention: A Symptom Network Analysis of Residual Symptoms in Bipolar Disorder

“…Previous research indicates that this could be linked to alterations in large-scale functional brain networks associated with BD’s residual depressive symptoms, potentially manifesting as a decline in the flexibility in cognitive control, salience detection, and emotion processing. 18 The presence of a loosely structured network of symptoms may be linked to disrupted brain connectivity correlates. In logistic regression, the main influencing factors related to residual symptoms were time from diagnosis to first treatment, MDQ1, MDQ2, QIDS score, PSYCH score, and ENVIR score.…”

Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes

“…Thus, reduced volumes of the segmented nuclei of the amygdala, rather than total volume, might be considered a potential risk factor for BD. Besides these structural alterations often found, there are several studies pointing out functional alterations for both the amygdala [ 25 , 26 ] and the hippocampus [ 27 , 28 ], which further highlights their important role in the pathophysiology of BD. Although these regions have been thoroughly analyzed in manifest BD, they have not been the object of investigation in individuals at risk.…”

Effects of Exercise on Functional Recovery in Patients with Bipolar Depression: A Study Protocol for a Randomized Controlled Trial

“…This pro-inflammatory state affects brain networks [ 45 , 46 ], particularly hippocampal neurogenesis [ 47 ]. Physical exercise reduces inflammation and stress, enhances hippocampal neurogenesis [ 28 ], and disrupts hippocampal connectivity in patients with BD [ 48 ]. Thus, stress, inflammation, and hippocampal neurogenesis may be promising candidates for providing the mechanistic grounds for our hypothesis.…”