Bipolar Disorder
Conditions
Keywords
Major Depressive or Manic Episodes, Bipolar, Mania, Depression, Lithium, fMRI, Pictures, Brain Scan
Brief summary
This study will assess the effects of bipolar disorder on brain activity and will determine if medication changes the brain activity in people with bipolar disorder.
Detailed description
Bipolar disorder (BD) is a chronic brain disorder that causes dramatic changes in a person's mood and energy. People with BD undergo periods of extreme happiness and extreme sadness, known as episodes of mania and depression. A person undergoing an episode of mania often experiences euphoric moods, increased energy, and aggressive behaviors, while a person in a depressed state often experiences low moods, lack of energy, and feelings of sadness. Researchers have recently discovered that abnormalities in certain brain areas that control emotion are often present in those with BD. It is believed that the severe mood shifts in BD may cause alterations in normal brain activity, specifically in corticolimbic activation and connectivity. Current mood stabilizing medications used to treat people with BD may help normalize these brain activity abnormalities. This study will assess the effects of BD on brain activity using functional magnetic resonance imaging (fMRI) and will determine if treatment with lithium changes the brain activity in people with BD. This 9-week study will include participants who are healthy, have BD, or are siblings of subject with BD. All potential participants will undergo initial testing, which will include a physical examination, blood tests, and an electrocardiogram (EKG). Participants will also be asked to answer questions about their mental health, drug use, personality, family history, and psychological well-being. Eligible participants will then return on a different day to undergo an MRI scan, taking 4 hours to complete. During the scan, participants will be asked to perform tasks designed to show changes in blood flow in specific brain regions. These tasks will include listening to sounds and looking at various letters, words, and pictures. This will mark the completion of the study for healthy participants, first degree relatives, and those participants with BD who do not wish to receive medication treatment. Following the first MRI scan, participants with BD who wish to undergo medication treatment will begin an 8-week course of lithium. Participants will be asked to come to the clinic at least once a week for medication monitoring visits. During these visits, participants will undergo blood draws and assessments on depression and mania. Participants will return for two repeat MRI scans after Weeks 2 and 8 of lithium treatment.
Interventions
DRUGLithium
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.
Sponsors
National Institute of Mental Health (NIMH)
Indiana University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 17-item Hamilton Depression Rating Scale (HDRS) | Measured at Baseline and after 8 weeks of treatment | 17-item HDRS is gold standard for measurement of depression with a range from 0 - 52. 10 - 14: mild depression; 14-20 moderate depression; \>20: severe and very severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale | Baseline and 8 weeks | Gold standard scale to measure mania, Range 0 - 60; 12 - 15 mild mania; 15 - 20 moderate mania; \>20 severe mania |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bipolar Depressed Subjects Treated With Lithium Participants with bipolar depression picture response during fMRI before and after treatment with lithium
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.
Depression and mania scores before and after treatment | 18 |
| Bipolar Manic Subjects Treated With Lithium Participants with bipolar mania picture response during fMRI before and after treatment with lithium
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.
Depression and mania scores before and after treatment | 22 |
| Bipolar Euthymic Subjects Treated With Lithium Participants with bipolar mania picture response during fMRI before and after treatment with lithium
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.
Depression and mania scores before and after treatment | 6 |
| Total | 46 |
Baseline characteristics
| Characteristic | Bipolar Depressed Subjects Treated With Lithium | Bipolar Manic Subjects Treated With Lithium | Bipolar Euthymic Subjects Treated With Lithium | Total |
|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 10 | 34 years STANDARD_DEVIATION 11 | 26 years STANDARD_DEVIATION 4 | 33 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 18 participants | 22 participants | 6 participants | 46 participants |
| Sex: Female, Male Female | 8 Participants | 15 Participants | 3 Participants | 26 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 3 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 46 |
| serious Total, serious adverse events | 0 / 46 |
Outcome results
Primary
17-item Hamilton Depression Rating Scale (HDRS)
17-item HDRS is gold standard for measurement of depression with a range from 0 - 52. 10 - 14: mild depression; 14-20 moderate depression; \>20: severe and very severe depression.
Time frame: Measured at Baseline and after 8 weeks of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Depressed Participants Treated | 17-item Hamilton Depression Rating Scale (HDRS) | Baseline 17-item HDRS | 20 units on a scale | Standard Deviation 4 |
| Bipolar Depressed Participants Treated | 17-item Hamilton Depression Rating Scale (HDRS) | After 8 weeks lithium treatment | 2 units on a scale | Standard Deviation 3 |
| Bipolar Manic Subjects Treated | 17-item Hamilton Depression Rating Scale (HDRS) | Baseline 17-item HDRS | 6 units on a scale | Standard Deviation 3 |
| Bipolar Manic Subjects Treated | 17-item Hamilton Depression Rating Scale (HDRS) | After 8 weeks lithium treatment | 3 units on a scale | Standard Deviation 2 |
| Bipolar Euthymic Subjects Treated | 17-item Hamilton Depression Rating Scale (HDRS) | Baseline 17-item HDRS | 6 units on a scale | Standard Deviation 4 |
| Bipolar Euthymic Subjects Treated | 17-item Hamilton Depression Rating Scale (HDRS) | After 8 weeks lithium treatment | 2 units on a scale | Standard Deviation 3 |
Secondary
Young Mania Rating Scale
Gold standard scale to measure mania, Range 0 - 60; 12 - 15 mild mania; 15 - 20 moderate mania; \>20 severe mania
Time frame: Baseline and 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bipolar Depressed Participants Treated | Young Mania Rating Scale | Baseline 17-item YMRS | 15 units on a scale | Standard Deviation 1 |
| Bipolar Depressed Participants Treated | Young Mania Rating Scale | Post 8 week treatment YMRS | 3 units on a scale | Standard Deviation 2 |
| Bipolar Manic Subjects Treated | Young Mania Rating Scale | Baseline 17-item YMRS | 3 units on a scale | Standard Deviation 2 |
| Bipolar Manic Subjects Treated | Young Mania Rating Scale | Post 8 week treatment YMRS | 2 units on a scale | Standard Deviation 3 |
| Bipolar Euthymic Subjects Treated | Young Mania Rating Scale | Baseline 17-item YMRS | 1 units on a scale | Standard Deviation 1 |
| Bipolar Euthymic Subjects Treated | Young Mania Rating Scale | Post 8 week treatment YMRS | 2 units on a scale | Standard Deviation 3 |