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

Mass General Brigham

Status

Active, not recruiting

Conditions

Major Depressive Episode

Bipolar Disorder

Bipolar Depression

Bipolar I Depression

Depression

Bipolar II Depression

Treatments

Drug: Lithium

Study type

Observational

Funder types

Other

Identifiers

NCT03336918

17-441

Details and patient eligibility

About

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.

Full 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).

Enrollment

120 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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) 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.

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.

Exclusion criteria for healthy subjects are: