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

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03336918

Collaborator

(none)

120

Enrollment

Location

83.8

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder Bipolar I Depression Bipolar II Depression Bipolar Depression Depression Major Depressive Episode	Drug: Lithium

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 Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Dec 7, 2017

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Bipolar Disorder I or II Depressed DSM-V Bipolar I or II Depressed treated with lithium	Drug: Lithium Open-label lithium treatment for Bipolar Disorder Subjects Healthy Controls only repeat testing - no intervention Other Names: Lithium carbonate or citrate or Lithium extended release
Healthy Controls Healthy Controls with no psychiatric history

Arm

Intervention/Treatment

Bipolar Disorder I or II Depressed

DSM-V Bipolar I or II Depressed treated with lithium

Drug: Lithium

Open-label lithium treatment for Bipolar Disorder Subjects Healthy Controls only repeat testing - no intervention

Other Names:

Lithium carbonate or citrate or Lithium extended release

Healthy Controls

Healthy Controls with no psychiatric history

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria for BD subjects:

ages 18-60 years (inclusive) and able to give voluntary informed consent;
Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for BD I or II, current Depressive Episode;
17-item Hamilton Depression Rating Scale (HAM-D) score >15 and <25;
Young Mania Rating Scale (YMRS) < 8;
no psychotropics in the last 2 weeks (if previously on fluoxetine then medication free for 5 weeks);
no lithium treatment for past 6 months;
satisfy criteria to undergo an MRI scan based on MRI screening questionnaire;
able to be managed as outpatients during the study as ascertained by Clinical Global Severity Scale < 5 (i.e., moderately ill) and no significant suicidal or homicidal ideation or gross disability.

Exclusion criteria for BD subjects are:

meeting DSM-IV criteria for schizophrenia, schizoaffective disorder, or an anxiety disorder as
a primary diagnosis;
requiring inpatient treatment;
meeting DSM-V criteria for substance dependence within the past 3 months, except caffeine or nicotine;
positive urinary toxicology screening at screening visit;
use of alcohol in the past 1 week;
serious medical or neurological illness;
current pregnancy or breast feeding;
metallic implants or other contraindications to MRI.

Inclusion criteria for healthy subjects:

ages 18-60 years and ability to give voluntary informed consent;
no history of psychiatric illness or substance abuse or dependence;
no significant family history of psychiatric or neurological illness in first degree relative;
not currently taking any prescription or centrally acting medications;
no use of alcohol in the past 1 week;
and no serious medical or neurological illness.