Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones
We propose to investigate structural and biochemical brain abnormalities in depressed subjects, and the relationship between the presence of such abnormalities and treatment outcome. We will recruit N=20 subjects with major depression disorder and N=20 matched normal controls. The depressed subjects would have previously not responded to an adequate trial with a selective serotonin reuptake inhibitor (SSRI). These depressed subjects will be treated for 4 weeks with the same SSRI antidepressant and with adjuvant triiodothyronine (T3). Structural magnetic resonance images (MRI) and then Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) data will be obtained two times for each patient (at the beginning and at the end of the study) and one time for the normal controls. We will measure for each depressed subject the number of white matter hyperintensities (WMH); we will also measure the degree of change from baseline in several compounds characteristic for the cellular high-energy phosphate metabolism: the phosphocreatine/inorganic phosphate ratio and the beta-nucleoside triphosphate. We will compare the severity of WMH and the high-energy phosphate metabolism in two groups of depressed subjects (those responding and those not responding to thyroid hormone augmentation) and the normal controls.
We hypothesize that:
- All depressed subjects, when compared with normal controls, will present lower baseline levels of compounds characteristic for the high-energy phosphate metabolism.
- Depressed subjects responding to T3 augmentation, when compared with subjects not responding to T3 augmentation, will present a larger increase of the high-energy phosphate metabolism.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Biochemical Brain Changes Correlated With The Antidepressant Effect Of Thyroid Hormones|
- change in depression (as measured by Ham-D-17) over the 4 weeks study [ Time Frame: 4 weeks ]
- change in bioenergetic metabolism (e.g., NTP and PCr) as measured by phosphorus magnetic resonance spectroscopy (P31-MRS) [ Time Frame: 4 weeks ]
|Study Start Date:||October 2001|
|Study Completion Date:||September 2004|
Drug: Cytomel (liothyronine)
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Dan V Iosifescu, MD||Massachusetts General Hospital|