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

Major Depressive Disorder Clinical Trial

Official title:

Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00188942
• Other study ID #: UHN REB 04-0204-B
• Secondary ID: CTA Control #095
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: February 6, 2013
• Start date: February 2005
• Est. completion date: June 2009

Study information

• Verified date: February 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Fluoxetine+Olanzapine

• Olanzapine

Procedure:
• Functional Magnetic Resonance Imaging

Locations

Country	Name	City	State
Canada	University Health Network - Toronto General Division	Toronto	Ontario
Canada	University Health Network - Toronto Western Division	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Eli Lilly and Company

Country where clinical trial is conducted

Canada, 

References & Publications (3)

Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003 Jan;160(1):64-75. — View Citation

Kumari V, Mitterschiffthaler MT, Teasdale JD, Malhi GS, Brown RG, Giampietro V, Brammer MJ, Poon L, Simmons A, Williams SC, Checkley SA, Sharma T. Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biol Psychiatry. 2003 Oct 15;54(8):777-91. — View Citation

Malhi GS, Lagopoulos J, Ward PB, Kumari V, Mitchell PB, Parker GB, Ivanovski B, Sachdev P. Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci. 2004 Feb;19(3):741-54. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.		6 weeks	No
Primary	17 Item - Hamilton Depression Rating Scale - Weekly		6 weeks	No
Primary	Clinical Global Impression - Improvement/Severity - Weekly		6 weeks	No
Primary	Young Mania Rating Scale - Weekly		6 weeks	No
Secondary	Positive Affect Negative Affect Scale		6 weeks	No
Secondary	Beck Depression Inventory		6 weeks	No
Secondary	State Trait Anxiety Index		6 weeks	No
Secondary	Behavioural Activation/Inhibition Scale		6 weeks	No
Secondary	SexFX Scale		6 weeks	No
Secondary	AMDP-5 Symptom Questionnaire		6 weeks	No