Dataset Information

Lithium monotherapy associated longitudinal effects on resting state brain networks in clinical treatment of bipolar disorder.

ABSTRACT:

Objectives

Lithium is one of the most effective and specific treatments for bipolar disorder (BP), but the neural mechanisms by which lithium impacts symptoms remain unclear. Past research has been limited by a reliance on cross-sectional designs, which does not allow for identification of within-person changes due to lithium and has not examined communication between brain regions (ie, networks). In the present study, we prospectively investigated the lithium monotherapy associated effects in vivo on the brain connectome in medication-free BP patients. In particular, we examined the within-person impact of lithium treatment on connectome indices previously linked to mania and depression in bipolar disorder.

Methods

Thirty-nine medication-free subjects - 26 BP (13 (hypo)manic and 13 depressed) and 13 closely matched healthy controls (HC) - were included. fMRI data were obtained at 3 timepoints: baseline, after 2 weeks, and after 8 weeks (total of 117 scans: 78 BP and 39 HC scans). BP subjects were clinically treated with lithium for 8 weeks while HC were scanned at the same time points but not treated. Graph theory metrics and repeated measures GLM were used to analyze lithium treatment associated effects.

Results

Consistent with hypotheses, lithium treatment was associated with a normalizing effect on mania-related connectome indices. Furthermore, shifts in both mania- and depression-related connectome indices were proportional to symptom change. Finally, lithium treatment-associated impact on amygdala function differed depending on baseline mood.

Conclusions

Present findings provide deeper insight into the therapeutic neural mechanisms associated with lithium treatment.

SUBMITTER: Spielberg JM

PROVIDER: S-EPMC8593846 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious neuroimaging studies have extensively demonstrated many signs of functionally spontaneous local neural activity abnormalities in bipolar disorder (BD) patients using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to identify the changes of voxel-wise whole-brain functional connectivity pattern and its corresponding functional connectivity changes remain largely unclear in BD patients. The current study aimed to investigate the voxel-wise changes of functional connectivity patterns in BD patients using publicly available data from the UCLA CNP LA5c Study.MethodsA total of 45 BD patients and 115 healthy control subjects were finally included and whole-brain functional connectivity homogeneity (FcHo) was calculated from their rs-fMRI. Moreover, the alterations of corresponding functional connectivity were subsequently identified using seed-based resting-state functional connectivity analysis.ResultsIndividuals with BD exhibited significantly lower FcHo values in the left middle temporal gyrus (MTG) when compared with controls. Functional connectivity findings further indicated decreased functional connectivities between left MTG and cluster 1 (left superior temporal gyrus, extend to middle temporal gyrus, rolandic operculum), cluster 2 (right postcentral, extend to right precentral) in BD patients. The mean FcHo values of left MTG were positively correlated with insomnia, middle scores and appetite increase scores. The mean functional connectivities of left MTG to cluster 1 were negatively correlated with grandiose delusions scores. While the functional connections between left MTG with cluster 2 were negatively correlated with delusions of reference and positively correlated with insomnia, middle scores in BD patients.ConclusionsOur findings suggested that abnormal FcHo and functional connections in those areas of the brain involving DMN and SMN networks might play a crucial role in the neuropathology of BD.