Dataset Information

Quantification of brain proton longitudinal relaxation (T₁ ) in lithium-treated and lithium-naive patients with bipolar disorder in comparison to healthy controls.

ABSTRACT:

Background

Proton longitudinal relaxation (T₁ ) is a quantitative MRI-derived tissue parameter sensitive to myelin, macromolecular, iron and water content. There is some evidence to suggest that cortical T₁ is elevated in bipolar disorder and that lithium administration reduces cortical T₁ . However, T₁ has not yet been quantified in separate groups containing lithium-treated patients, lithium-naïve patients, and matched healthy controls.

Methods

Euthymic patients with bipolar disorder receiving lithium (n = 18, BDL) and those on other medications but naïve to lithium (n = 20, BDC) underwent quantitative T₁ mapping alongside healthy controls (n = 18, HC). T₁ was compared between groups within the cortex, white matter and subcortical structures using regions of interest (ROI) derived from the Desikan-Killiany atlas. Effect sizes for each ROI were computed for BDC vs BDL groups and Bipolar Disorder vs HC groups.

Results

No significant differences in T₁ were identified between BDL and BDC groups when corrected for multiple comparisons. Patients with bipolar disorder had significantly higher mean T₁ in a range of ROIs compared to healthy controls, including bilateral motor, somatosensory and superior temporal regions, subcortical structures and white matter.

Conclusions

The higher T₁ values observed in the patients with bipolar disorder may reflect abnormal tissue microstructure. Whilst the precise mechanism remains unknown, these findings may have a basis in differences in myelination, macromolecular content, iron and water content between patients and controls.

SUBMITTER: Necus J

PROVIDER: S-EPMC7891392 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Quantification of brain proton longitudinal relaxation (T<sub>1</sub> ) in lithium-treated and lithium-naïve patients with bipolar disorder in comparison to healthy controls.

Necus Joe J Smith Fiona Elizabeth FE Thelwall Peter Edward PE Flowers Carly Jay CJ Sinha Nishant N Taylor Peter Neal PN Blamire Andrew Matthew AM Wang Yujiang Y Cousins David Andrew DA

Bipolar disorders 20191202 1

<h4>Background</h4>Proton longitudinal relaxation (T<sub>1</sub> ) is a quantitative MRI-derived tissue parameter sensitive to myelin, macromolecular, iron and water content. There is some evidence to suggest that cortical T<sub>1</sub> is elevated in bipolar disorder and that lithium administration reduces cortical T<sub>1</sub> . However, T<sub>1</sub> has not yet been quantified in separate groups containing lithium-treated patients, lithium-naïve patients, and matched healthy controls.<h4>Me ...[more]

PMID: 31755171

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Project description:BackgroundLithium, one of the few effective treatments for bipolar depression (BPD), has been hypothesized to work by enhancing serotonergic transmission. Despite preclinical evidence, it is unknown whether lithium acts via the serotonergic system. Here we examined the potential of serotonin transporter (5-HTT) or serotonin 1A receptor (5-HT1A) pre-treatment binding to predict lithium treatment response and remission. We hypothesized that lower pre-treatment 5-HTT and higher pre-treatment 5-HT1A binding would predict better clinical response. Additional analyses investigated group differences between BPD and healthy controls and the relationship between change in binding pre- to post-treatment and clinical response. Twenty-seven medication-free patients with BPD currently in a depressive episode received positron emission tomography (PET) scans using 5-HTT tracer [11C]DASB, a subset also received a PET scan using 5-HT1A tracer [11C]-CUMI-101 before and after 8 weeks of lithium monotherapy. Metabolite-corrected arterial input functions were used to estimate binding potential, proportional to receptor availability. Fourteen patients with BPD with both [11C]DASB and [11C]-CUMI-101 pre-treatment scans and 8 weeks of post-treatment clinical scores were included in the prediction analysis examining the potential of either pre-treatment 5-HTT or 5-HT1A or the combination of both to predict post-treatment clinical scores.ResultsWe found lower pre-treatment 5-HTT binding (p = 0.003) and lower 5-HT1A binding (p = 0.035) were both significantly associated with improved clinical response. Pre-treatment 5-HTT predicted remission with 71% accuracy (77% specificity, 60% sensitivity), while 5-HT1A binding was able to predict remission with 85% accuracy (87% sensitivity, 80% specificity). The combined prediction analysis using both 5-HTT and 5-HT1A was able to predict remission with 84.6% accuracy (87.5% specificity, 60% sensitivity). Additional analyses BPD and controls pre- or post-treatment, and the change in binding were not significant and unrelated to treatment response (p > 0.05).ConclusionsOur findings suggest that while lithium may not act directly via 5-HTT or 5-HT1A to ameliorate depressive symptoms, pre-treatment binding may be a potential biomarker for successful treatment of BPD with lithium.Clinical trial registrationPET and MRI Brain Imaging of Bipolar Disorder Identifier: NCT01880957; URL: https://clinicaltrials.gov/ct2/show/NCT01880957.

Dataset Information

Quantification of brain proton longitudinal relaxation (T₁ ) in lithium-treated and lithium-naive patients with bipolar disorder in comparison to healthy controls.

Background

Methods

Results

Conclusions

Publications

Quantification of brain proton longitudinal relaxation (T<sub>1</sub> ) in lithium-treated and lithium-naïve patients with bipolar disorder in comparison to healthy controls.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Quantification of brain proton longitudinal relaxation (T1 ) in lithium-treated and lithium-naive patients with bipolar disorder in comparison to healthy controls.

Background

Methods

Results

Conclusions

Publications

Quantification of brain proton longitudinal relaxation (T<sub>1</sub> ) in lithium-treated and lithium-naïve patients with bipolar disorder in comparison to healthy controls.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Quantification of brain proton longitudinal relaxation (T₁ ) in lithium-treated and lithium-naive patients with bipolar disorder in comparison to healthy controls.