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

NCT ID: NCT03336918

Last Updated: 2025-07-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2025-12-01

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).

Conditions

Bipolar Disorder; Bipolar I Depression; Bipolar II Depression; Bipolar Depression; Depression; Major Depressive Episode

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Bipolar Disorder I or II Depressed

DSM-V Bipolar I or II Depressed treated with lithium

Lithium

Intervention Type: DRUG

Open-label lithium treatment for Bipolar Disorder Subjects

Healthy Controls only repeat testing - no intervention

Healthy Controls

Healthy Controls with no psychiatric history

No interventions assigned to this group

Interventions

Lithium

Open-label lithium treatment for Bipolar Disorder Subjects

Healthy Controls only repeat testing - no intervention

Intervention Type: DRUG

Other Intervention Names

Lithium carbonate or citrate or Lithium extended release

Eligibility Criteria

Inclusion Criteria

• 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) OR on stable psychotropic medications for 12 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.

• 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.

Exclusion Criteria

• 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.

• under 18 years of age;
• pregnant or breast-feeding;
• metallic implants or other contraindication to MRI.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Amit Anand

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amit Anand, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Foundation Center for Behavioral Health

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

17-441

Identifier Type: -

Identifier Source: org_study_id