A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder

University Health Network, Toronto

Status and phase

Completed

Phase 4

Conditions

Major Depressive Disorder

Treatments

Drug: Fluoxetine+Olanzapine

Procedure: Functional Magnetic Resonance Imaging

Drug: Olanzapine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00188942

UHN REB 04-0204-B

CTA Control #095694

Details and patient eligibility

About

This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Depressed patients will be treated with a combination of fluoxetine and olanzapine and undergo MRI scans before, during, and after pharmacotherapy.

Full description

The purpose of this study is to further characterize the neural correlates of affective processing in BD and MDD subjects using fMRI. Subjects who meet criteria for a major depressive episode in the context of BD (n=15); MDD (n=15) and a group of psychiatrically unaffected control subjects (CS, n=15) will undergo four fMRI scans while experiencing a temporary mood induction through the presentation of affective imagery from the International Affective Picture System (IAPS). Both BD and MDD subjects will receive the same combination pharmacotherapy to treat the depression, with fMRI data acquired before, and 1, 3, 6 weeks following pharmacotherapy initiation. Positive, negative, and neutral affective visual stimuli will be presented in a blocked design.

Comparison(s): The effects of time and group will be analyzed in factorial models. Regions of interest that demonstrate significant group-by-time interactions will be further correlated with self-report and clinician-rated psychometric indices.

Enrollment

42 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: (All three groups)

age 18-55 years
satisfactory physical health
education level and a degree of understanding to communicate effectively with the investigator c
capable of providing informed consent
female subjects of childbearing potential, a medically accepted means of contraception.

Additional inclusion criteria for the patient groups include

DSM-IV-TR criteria for a diagnosis of BD or MDD
currently meeting criteria for an MDE and
a Hamilton Depression Rating Scale 17 Item (HDRS-17) score of > 17
blood indices within normal clinical ranges.

Exclusion Criteria: (All three groups)

DSM-IV-TR criteria for substance abuse or dependence (except nicotine or caffeine) within the past 6 months
comorbid neurological or other major psychiatric disorders as defined in the DSM-IV-TR;
history of neurological trauma resulting in loss of consciousness;
uncorrected hypothyroidism or hyperthyroidism, including elevated thyroid stimulating hormone (TSH);
other unstable medical condition;
female subjects who are pregnant or nursing;

Additional exclusion criteria for the BD and MDD group include:

prior failure to respond to fluoxetine and olanzapine in combination at adequate dose and duration;
evidence of serious risk of suicide based on clinician assessment and/or HRSD suicide item > 3;
course of ECT (electroconvulsive therapy) in the preceding 6 months;
Young Mania Rating Scale (YMRS) > 7;
administration of fluoxetine within previous 4 weeks;
treatment resistance as defined by the failure of two antidepressant trials from dissimilar classes
Hyperglycemia or diabetes mellitus as defined by a fasting blood glucose value of > 125 mg/dl.