Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder

Abstract

Objectives. Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods. A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results. Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions. This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.

Lipid Biomarker Research in Bipolar Disorder: A Scoping Review of Trends, Challenges, and Future Directions

“…Notably, studies indicate that dysregulation of phospholipid metabolism and lipid peroxidation due to oxidative stress are important ( 13 , 15 , 18 , 19 , 20 ). Moreover, there is a strong association between neuropsychiatric disorders and the development of dyslipidemia and cardiovascular disease ( 20 , 21 , 22 , 23 , 24 ), as well as other inflammatory conditions with alterations in lipid metabolic pathways involved in the immune system, such as arachidonic acid metabolism ( 14 , 25 , 26 ). Furthermore, recent genome-wide association studies have uncovered overlap between susceptibility loci for neuropsychiatric disorders like schizophrenia and BD and genes linked to the regulation of lipid levels ( 27 , 28 , 29 ).…”

Functional connectivity of the default mode network subsystems in patients with major depressive episodes with mixed features

“… 33 As noted, bipolar disorder patients have functional changes in brain regions related to autobiographical memory retrieval. 34 Hence, our findings suggest that abnormal connectivity within the MTL subsystem may imply a dysfunctional encoding of episodic memory in patients with MMF, but this may not be specific because the patients with MDD noMF also showed abnormality in this subsystem.…”

Global Functional Connectivity Analysis Indicating Dysconnectivity of the Hate Circuit in Major Depressive Disorder

“…where the Pearson correlation coefficient ( r ) of time series Ts for a pair of given voxels a and b was calculated. Finally, the mean correlation coefficient within the gray matter mask of the entire brain was calculated using the MATLAB software ( Scheinost et al, 2016 ; Pan et al, 2021 ), and the data were normalized and converted into z -values using Fisher r -to- z transformation ( Cole et al, 2010 ; Kaneoke et al, 2012 ; Thompson and Fransson, 2016 ).…”

“…Global-brain functional connectivity is a measurement tool that computes the mean time series correlation between a given voxel with every other voxel for an unbiased method to determine the location of abnormal FCs (Anticevic et al, 2013(Anticevic et al, , 2014Murrough et al, 2016;Pan et al, 2019Pan et al, , 2021. The gray matter mask is produced by using the gray matter probability map (probability > 0.2) in the SPM8 software (Donishi et al, 2018).…”