Effects of Cognitive Behavioral Therapy on Brain Serotonin Activity in People With Depression
Effects of Cognitive Behavioral Therapy on Brain Serotonin Activity in People With Depression
This study will examine changes in brain serotonin activity in people with depression before
 and after they receive cognitive behavioral therapy.
Depression is a serious illness that affects almost 19 million adults in the United States
 each year. Common symptoms of depression include persistent feelings of anxiety, guilt, or
 hopelessness; irregular sleep and appetite patterns; lethargy; disinterest in previously
 enjoyed activities; excessive irritability and restlessness; suicidal thoughts; and inability
 to concentrate. A person's depression can be attributed to a variety of causes, including
 biological and genetic factors, environmental influences, or developmental experiences. Among
 biological factors, a recently researched possible cause is the altered activity of
 specialized areas on brain nerve cells called serotonin receptors, which have been found to
 be at reduced levels in people with depression. The hormone serotonin is known to naturally
 influence mood, making depression treatments that aim to increase levels of serotonin
 important. Treatment for depression with cognitive behavioral therapy (CBT), which teaches
 ways to modify thoughts and behaviors that contribute to depression, may help in raising
 brain serotonin levels and in improving depressive symptoms. This study will examine changes
 in brain serotonin activity using single photon emission computed tomography (SPECT) imaging
 in people with depression before and after they receive CBT. The study will also use SPECT
 imaging to compare brain serotonin activity of non-depressed healthy participants with that
 of depressed participants.

 Participation in this study will last between 12 and 14 weeks. All participants will first
 undergo an initial evaluation that will include questions about medical history, a physical
 exam, a blood draw, a urine test, and an electrocardiogram (ECG). Participants will then
 undergo an ADAM (a selective radioligand for SPECT imaging) SPECT scan. During the ADAM SPECT
 scan visit, participants will undergo an injection of the ADAM, an ECG, blood pressure
 monitoring, and a 60-minute SPECT scan. If necessary, participants may also be asked to have
 a magnetic resonance imaging (MRI) brain scan after completing the SPECT scan.

 Depressed participants will then attend at least once weekly CBT sessions for 12 weeks.
 During the 45-minute sessions, participants will meet with a therapist to learn ways to
 adjust thoughts and behaviors that may be adding to their depression. After completing the 12
 weeks of CBT, all participants will be re-evaluated by a study doctor and, if still in good
 health, will undergo a repeat ADAM SPECT scan.
Inclusion Criteria:

 -  DSM-IV diagnosis of major depressive disorder (MDD)

 -  Drug naive from prior psychotropic medication for more than 6 months before study
 entry

 -  Hamilton-Depression (HAM-D) 17 score greater than or equal to 16

 -  Woman of childbearing age with a negative pregnancy test within 48 hours of scanning

 Exclusion Criteria:

 -  DSM-IV Axis I diagnosis other than MDD

 -  Use of psychotropic medication within 6 months of study entry

 -  History of bipolar disorder

 -  Current alcohol or drug abuse/dependence within 6 months of study entry

 -  History of sensitivity or intolerance to s-citalopram

 -  Medical contraindication to the use of s-citalopram

 -  Unstable medical condition (e.g., angina pectoris, untreated hypertension)

 -  Pregnant or nursing

 -  Woman of childbearing potential not using a medically acceptable form of birth control

 -  Actively suicidal or requiring hospitalization

 -  Requiring additional psychotropic drug therapy

 -  History of transient ischemic attacks

 -  History of cerebral infarction (including lacunar infarct with symptoms more than 24
 hours in duration)

 -  History of Binswanger's disease or a history of hypertensive encephalopathy

 -  History of intracranial hemorrhage

 -  History of head trauma with loss of consciousness

 -  History of encephalitis

 -  History of extended exposure to known neurotoxin (e.g., cyanide, carbon monoxide)

 -  Uncontrolled metabolic disorder (e.g., thyroid disease, diabetes mellitus)

 -  History of cognitive impairment other than major depressive episode

 -  History of normal pressure hydrocephalus

 -  History of cancer metastatic to the central nervous system

 -  History of Parkinson's or other basal ganglia disease

 -  History of Guillain-Barré syndrome (chronic or relapsing polyneuropathy)

 -  Inability to undergo an MRI scan