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

Condition(s) targeted: Bipolar Disorder; Major Depressive Disorder

Intervention: Fluoxetine (Drug); Olanzapine (Drug); Functional Magnetic Resonance Imaging (Procedure)

Phase: Phase 4

Status: Recruiting

Sponsored by: University Health Network, Toronto

Official(s) and/or principal investigator(s):
Sidney H. Kennedy, MD, FRCPC, Principal Investigator, Affiliation: University Health Network, Department of Psychiatry, University of Toronto

Overall contact:
Sidney H Kennedy, MD, FRCPC, Phone: 416 340 3888, Email: sidney.kennedy@uhn.on.ca

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.

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

Study design: Diagnostic, Non-Randomized, Open Label, Active Control, Single Group Assignment, Pharmacodynamics Study

Primary outcome:

MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.

17 Item - Hamilton Depression Rating Scale - Weekly

Clinical Global Impression - Improvement/Severity - Weekly

Young Mania Rating Scale - Weekly

Secondary outcome:

Positive Affect Negative Affect Scale

Beck Depression Inventory

State Trait Anxiety Index

Behavioural Activation/Inhibition Scale

SexFX Scale

AMDP-5 Symptom Questionnaire

Detailed 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.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

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.

Sidney H Kennedy, MD, FRCPC, Phone: 416 340 3888, Email: sidney.kennedy@uhn.on.ca

University Health Network - Toronto Western Division, Toronto, Ontario M5T2S8, Canada; Recruiting
Roger S. McIntyre, MD, FRCPC, Phone: 416 603 5279, Email: roger.mcintyre@uhn.on.ca
Roger S. McIyntyre, MD, FRCPC, Principal Investigator

University Health Network - Toronto General Division, Toronto, Ontario M5G2C4, Canada; Recruiting
Sidney H. Kennedy, MD, FRCPC, Phone: 416 340 3888, Email: sidney.kennedy@uhn.on.ca
Sidney H. Kennedy, MD, FRCPC, Principal Investigator

Related publications:

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.

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.

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.

Starting date: February 2005
Ending date: December 2006
Last updated: October 18, 2006