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Functional Connectivity in Mood Regulating Circuit In Bipolar Depression and Mania

Primary Purpose

Bipolar Depression

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Lithium

About this trial

This is an interventional prevention trial for Bipolar Depression focused on measuring Mood Regulating Circuit, Lithium, fMRI

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Inclusion criteria for Bipolar Subjects

Ages 18-60 years and able to give voluntary informed consent.
Satisfy criteria for Bipolar Depression using the Structured Clinical Interview for Diagnostic and Statistical Manual -4th edition (DSM-IV) (SCID-IV).
Bipolar depressed subjects: 25-item Hamilton Depression Rating Scale (HDRS) score > 18.Young Mania Rating Score (YMRS)<10.
Bipolar hypomanic/manic subjects will have a YMRS score>12 and a 25-item HDRS score<10.
Bipolar Euthymic subjects will have YMRS score < 10 and HDRS score < 10 and would have been euthymic for > 14 days.
Subjects will be drug and medication free and would have no significant history of medical or neurological illness.
Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire
Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following:
- Symptoms not worsening by more than 10 points on either the HDRS or the YMRS during the course of the study.
- No danger to self or others.
- No psychotic symptoms.

Inclusion criteria for Healthy Subjects:

Ages 18-60 years and able to give voluntary informed consent.
No history of psychiatric illness or substance abuse or dependence as assessed by SCID for non-patients (SCID-NP).
No significant family history of psychiatric or neurological illness.
Not currently taking any prescription or centrally acting medications.
No serious medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry.

Exclusion Criteria:

Exclusion criteria for Bipolar Subjects

Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder.
Use of neuroleptic past 2 weeks
Use of antidepressants in the past 2 weeks. If on fluoxetine in the past then should not have been on this medication for 4 weeks.
Use of mood stabilizers in the past 2 weeks
Use of benzodiazepines in the past 2 weeks.
Acutely suicidal or homicidal or requiring inpatient treatment.
Meeting DSM-IV criteria for other substance dependence within the past year, except caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening initially and on test days.
Use of alcohol in the past 1 week.
No serious medical or neurological illness as assessed by physical examination and laboratory examination including complete blood count (CBC) and blood chemistry.
Current pregnancy or breast feeding.
Metallic implants.
Previously known positive Human Immunodeficiency Virus (HIV) blood test as reported by the subject.

Exclusion criteria for Healthy Subjects:

Under 18 years of age.
Pregnant or breast feeding.

Sites / Locations

Indiana University Adult Psychiatry Clinic

Outcomes

Primary Outcome Measures

Comparative activation of amygdala and cortico-amydalar connectivity as measured by fMRI taken at baseline and eight weeks from baseline

Improvement of scores on Hamilton Depression Rating Scale given weekly for eight weeks

Secondary Outcome Measures

Improvement as measured by the Clinical Global Impression Severity and Improvement Scales given weekly for eight weeks

Improvement as measured by the Brief Psychiatric Rating Scale given weekly for eight weeks

Full Information

NCT ID

NCT00457054

First Posted

September 14, 2005

Last Updated

September 27, 2011

Sponsor

Indiana University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT00457054

Brief Title

Functional Connectivity in Mood Regulating Circuit In Bipolar Depression and Mania

Official Title

Functional Connectivity in Mood Regulating Circuit In Bipolar Depression and Mania Before and After Lithium Treatment: An Brain fMRI Study

Study Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

July 2003 (undefined)

Primary Completion Date

March 2007 (Actual)

Study Completion Date

March 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Indiana University School of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to find out what parts of the brain have increased or decreased activity with individuals who have bipolar disorder and how medicine changes this activity in bipolar subjects. Another purpose of this study is to compare data obtained from bipolar depressed subjects with data obtained from healthy subjects. In this study we will measure activity in different parts of the brain, while participants see pictures, using Magnetic Resonance Imaging (MRI) scan. We will do two MRI scans with each subject before and after treatment for eight weeks with a standard bipolar disorder medication called lithium.

Detailed Description

Aim 1: Our first aim is to use a novel fMRI experimental paradigm to investigate the pathophysiology of bipolar disorder (BD) in terms of the strength of connectivity (as measured by LFBF correlations) between the different emotion regulating areas of the brain rather than in terms of increase or decrease in localized brain activity. Specific Aim 2: Our second aim is to investigate whether lithium works by altering the connectivity of areas of the brain implicated in the pathophysiology of BD, thereby leading to changes in the abnormal positive or negative emotional reactions to the environment seen in mania and depression respectively. Specific Aim 3: Out third aim is to investigate whether patients with the s/s or s/L alleles of the 5-HTTLPR polymorphism will have greater amygdalar activation and decreased cortico-amygdala connectivity compared to patients with L/L genotype. We will also investigate whether lithium treatment differentially affects these fMRI measures in the s/s or s/L and L/L genotypes. Methods: We will study unmedicated subjects satisfying DSM-IV criteria for Bipolar Disorder current episode depressed or hypomanic/manic or who are euthymic. Subjects will undergo fMRI before and after 8 weeks of treatment with lithium a mood stabilizer that is known to be effective in both phases of BD. Healthy subjects will have a scan at baseline and after 8 weeks but will not be treated with any medication. We will also test for the serotonin transporter gene (the gene that controls the availability of a chemical called serotonin in the brain), which has been shown to effect how lithium works.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bipolar Depression

Keywords

Mood Regulating Circuit, Lithium, fMRI

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Lithium

Intervention Description

starting dose 600 mg increase as tolerated

Primary Outcome Measure Information:

Title

Comparative activation of amygdala and cortico-amydalar connectivity as measured by fMRI taken at baseline and eight weeks from baseline

Time Frame

07-03 to 3-07

Title

Improvement of scores on Hamilton Depression Rating Scale given weekly for eight weeks

Time Frame

07-03 to 3-07

Secondary Outcome Measure Information:

Title

Improvement as measured by the Clinical Global Impression Severity and Improvement Scales given weekly for eight weeks

Time Frame

07-03 to 3-07

Title

Improvement as measured by the Brief Psychiatric Rating Scale given weekly for eight weeks

Time Frame

07-03 to 3-07

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Inclusion criteria for Bipolar Subjects Ages 18-60 years and able to give voluntary informed consent. Satisfy criteria for Bipolar Depression using the Structured Clinical Interview for Diagnostic and Statistical Manual -4th edition (DSM-IV) (SCID-IV). Bipolar depressed subjects: 25-item Hamilton Depression Rating Scale (HDRS) score > 18.Young Mania Rating Score (YMRS)<10. Bipolar hypomanic/manic subjects will have a YMRS score>12 and a 25-item HDRS score<10. Bipolar Euthymic subjects will have YMRS score < 10 and HDRS score < 10 and would have been euthymic for > 14 days. Subjects will be drug and medication free and would have no significant history of medical or neurological illness. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following: Symptoms not worsening by more than 10 points on either the HDRS or the YMRS during the course of the study. No danger to self or others. No psychotic symptoms. Inclusion criteria for Healthy Subjects: Ages 18-60 years and able to give voluntary informed consent. No history of psychiatric illness or substance abuse or dependence as assessed by SCID for non-patients (SCID-NP). No significant family history of psychiatric or neurological illness. Not currently taking any prescription or centrally acting medications. No serious medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry. Exclusion Criteria: Exclusion criteria for Bipolar Subjects Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder. Use of neuroleptic past 2 weeks Use of antidepressants in the past 2 weeks. If on fluoxetine in the past then should not have been on this medication for 4 weeks. Use of mood stabilizers in the past 2 weeks Use of benzodiazepines in the past 2 weeks. Acutely suicidal or homicidal or requiring inpatient treatment. Meeting DSM-IV criteria for other substance dependence within the past year, except caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening initially and on test days. Use of alcohol in the past 1 week. No serious medical or neurological illness as assessed by physical examination and laboratory examination including complete blood count (CBC) and blood chemistry. Current pregnancy or breast feeding. Metallic implants. Previously known positive Human Immunodeficiency Virus (HIV) blood test as reported by the subject. Exclusion criteria for Healthy Subjects: Under 18 years of age. Pregnant or breast feeding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amit Anand, MD

Organizational Affiliation

Indiana University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University Adult Psychiatry Clinic

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

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Functional Connectivity in Mood Regulating Circuit In Bipolar Depression and Mania

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