Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder

Recruiting

• Conditions: Bipolar Disorder; Major Depressive Episode; Bipolar II Depression; Bipolar I Depression; Depression; Bipolar Depression
• Interventions: Drug: Lithium

• Registration Number: NCT03336918
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.

Detailed Description

The premise of this proposal is that the clinical efficacy of lithium in bipolar disorder, and its complex effects on multiple brain physiological functions, may be best deciphered using a network properties-metric approach. This approach is critical because it provides insight into the function of brain networks (e.g., resilience to disruption, central hubs), which is likely to be more closely linked to behavioral outcomes. Furthermore, we will conduct an exploratory investigation of the in vivo molecular effects of lithium by measuring peripheral gene expression. To bring these together, we will also explore whether connectome changes serve as mediator between molecular changes (i.e., gene expression) induced by lithium treatment and behavioral changes (e.g., depression, mood stability, suicidality).

Study Timeline

• Study First Submitted: 2017-10-05
• Study First Submitted QC: 2017-11-06
• Study First Posted: 2017-11-08
• Study Start: 2017-12-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-08
• Primary Completion: 2025-08-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Bipolar Disorder I or II Depressed	Lithium	DSM-V Bipolar I or II Depressed treated with lithium

Primary Outcome Measures

Name	Time	Method
Functional Connectivity (Fc) changes	2, 8, 26 weeks	Investigate effects of lithium monotherapy treatment of BD on changes in Fc through fMRI imaging from baseline after 2, 8, and 26 weeks of treatment and test whether these changes correlate with improvement in state-related symptoms and longer term mood stability. Healthy controls will also be scanned at the same time points but not treated.
Structural Connectivity (Sc) changes	2, 8, 26 weeks	Investigate effects of lithium monotherapy treatment of BD depression on changes in the diffusion weighted imaging Sc through fMRI imaging from baseline after 2, 8, and 26 weeks and test whether these changes correlate with depression severity and mood stability. Healthy controls will also be scanned at the same time points but not treated.

Secondary Outcome Measures

Name	Time	Method
Changes in peripheral gene expression	2, 8, 26 weeks	An exploratory investigation of whether lithium-related changes in the functional and structural connectome over time represent a link between shifts in peripheral gene expression and improvement in illness-related measures.Lithium therapy will be associated with changes in gene expression pathways such as the mitochondrial-carnitine shuttle pathway, which in turn will be related to changes in the functional and structural connectome.

Trial Locations

Locations (1)

Cleveland Clinic Foundation Center for Behavioral Health; 🇺🇸 Cleveland, Ohio, United States