Intervention: Lithium
Trial phase: Phase 4
ATC code: N05AN01
SMILES: [Li]
Sex: All
Age groups: Child | Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 46
Group description: Participants with bipolar disorder who undergo fMRI and lithium treatment

Lithium: Dosing will start as one 300-mg capsule per day and will be titrated up to four 300-mg capsules per day for a total of 8 weeks of treatment.

Picture response during fMRI: While undergoing an fMRI scan, participants will be presented with pictures, letters, words, and sounds to evoke emotional responses. There will be a maximum of three MRI scans over 9 weeks.

Adverse Events information was collected irrespective of the sub-grouping
Eligibility criteria:
Inclusion criteria for BD participants:

Meets DSM-IV criteria for bipolar I or II disorder
Meets criteria to undergo an MRI scan based on MRI screening questionnaire
Suited for outpatient care during the study as ascertained by a score of less than 5 on the Clinical Global Severity Scale, no significant suicidal or homicidal ideation, and no severe disability

Inclusion criteria for BD depressed participants:

Meets criteria for DSM-IV depressive episode-current
Score of greater than 15 but less than 30 on the 17-item HDRS
Score of less than 12 on the Young Mania Rating Scale

Inclusion criteria for BD (hypo) manic participants:

Meets criteria for DSM-IV manic episode-current
Score of less than or equal to 18 on the 17-item HDRS
Score of greater than 12 but less than 25 on the Young Mania Rating Scale

Inclusion criteria for BD euthymic patients:

Satisfy criteria for DSM-IV for euthymic state-current for at least 2 weeks.
17-item Hamilton Depression Rating Scale < 12; Young Mania Rating Scale score < 10

Exclusion criteria for BD participants:

Meets DSM-IV criteria for unipolar depression, schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, anxiety disorder as a primary diagnosis, mental retardation, or personality disorder
Received electroconvulsive therapy in the 12 months prior to study entry
Use of neuroleptics, mood stabilizers, or benzodiazepines in the 2 weeks prior to study entry
Use of antidepressants in the 2 weeks prior to study entry
Use of fluoxetine in the 5 weeks prior to study entry
Use of lithium in the 6 months prior to study entry
Acutely suicidal or homicidal or requiring inpatient treatment
Meets DSM-IV criteria for substance/alcohol dependence, excluding caffeine or nicotine, in the 6 months prior to study entry or substance/alcohol abuse in the 3 months prior to study entry
Use of alcohol in the 1 week prior to study entry and refusal to avoid alcohol use during the course of the study
Presence of serious acute or chronic medical or neurological illness, including previously known HIV positive status (due to possible CNS involvement) as assessed by history, physical examination, and laboratory examination
Pregnant or breastfeeding
Metallic implants or other contraindication to MRI

Inclusion criteria for first degree relatives of bipolar disorder subjects:

Ages 15-60 years (inclusive) and able to give voluntary informed consent.
Have never satisfied criteria for DSM-IV BD.
Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire.
17-item Hamilton Depression Rating Scale < 10; Young Mania Rating Scale score < 10

Exclusion criteria for first degree relatives of bipolar disorder subjects:

Under 15 years of age.
Meeting DSM-IV criteria for current episode of unipolar depression
Pregnant or breast feeding.
Metallic implants or other contraindication to MRI.
Currently taking any prescription or centrally acting medications.
Serious acute or chronic medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry.
Use of alcohol in the past 1 week and not being able to avoid alcohol use during the course of the study.

Inclusion criteria for healthy subjects:

Ages 18-60 years (inclusive) and able to give voluntary informed consent.
No current or past history of psychiatric illness or substance abuse or dependence.
No current or past history of psychiatric illness or substance abuse or dependence in a first degree relative.

Exclusion criteria for healthy participants:

Under 18 years of age
Pregnant or breastfeeding
Metallic implants or other contraindication to MRI
Significant family history of psychiatric or neurological illness
Currently taking any prescription or centrally acting medications
Serious acute or chronic medical or neurological illness as assessed by history, physical examination, and laboratory examination
Use of alcohol in the 1 week prior to study entry and refusal to avoid alcohol use during the course of the study