Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
This study will examine changes in brain dopamine transporter activity before and after
 antidepressant therapy.
Depression is a serious psychiatric disorder that affects about 10% of the adult population
 in the United States in a given year. Common symptoms of depression include a persistent down
 mood and disinterest in previously enjoyed activities, often causing strain on work, social,
 and family life. A person's depression can be attributed to a variety of causes, including
 physiological and sociological factors. Among physiological factors, dopamine (DA), a
 chemical associated with feelings of happiness and pleasure, may play a key role in the onset
 of depression and may also be involved in the beneficial effect of antidepressant medication.
 Recent studies have found that people with depression have increased DA transporter (DAT)
 levels in a specific region of the inner brain called the striatum. The increased DAT levels
 might reflect alterations in central DA function. Treatment for depression with selective
 serotonin reuptake inhibitor (SSRI) antidepressant therapy may help in returning DAT levels
 to normal and in improving depressive symptoms. Using single photon emission computed
 tomography (SPECT) imaging, this study will examine changes in brain DAT activity in people
 with depression before and after they receive SSRI antidepressant therapy or cognitive
 behavioral therapy (CBT).

 Participation in this study will last about 14 weeks and will involve participants who are
 healthy and depressed. All participants will first undergo baseline assessments that will
 include a medical history, questions about current and past health, a physical exam, a blood
 draw, a urine sampling, and an electrocardiogram (ECG). After completing the baseline
 assessments, participants will undergo a TRODAT-1 SPECT scan, which will involve an injection
 of TRODAT-1 (a radioactive agent to measure DA) and, after a 3-hour break, a 75-minute SPECT
 scan. If necessary, participants may also be asked to have a magnetic resonance imaging (MRI)
 brain scan after completing the SPECT scan.

 Participants with depression will then be assigned randomly to undergo 12 weeks of treatment
 with either the antidepressant medication s-citalopram or CBT. Participants assigned to take
 s-citalopram will return for study visits weekly for 2 weeks, every other week for 6 weeks,
 and then monthly for 4 weeks. During study visits, participants will receive their
 medication, answer questions about depression and medication side effects, and occasionally
 fill out general health questionnaires. Participants receiving CBT will attend twice weekly
 sessions for 2 weeks and then once weekly sessions for 10 weeks. Sessions will focus on
 modifying thoughts and behaviors that may contribute to depression. After 12 weeks, all
 participants will be re-evaluated by a study doctor and, if still in good health, will
 undergo a repeat TRODAT-1 SPECT scan.
Inclusion Criteria:

 -  DSM-IV diagnosis of major depressive episode (MDE) or major depressive disorder (MDD)

 -  Drug free of psychotropic medication for more than 6 months before study entry

 -  17-item Hamilton Depression Scale (HAM-D17) score of greater than 16

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

 -  Absence of DSM-IV Axis I diagnosis as determined by Structured Clinical Interview for
 DSM Disorders (SCID)

 Exclusion Criteria:

 -  DSM-IV Axis I diagnosis other than MDE

 -  History of mania

 -  Current alcohol or drug abuse, or alcohol or drug dependence within 6 months before
 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 breastfeeding

 -  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 that last more
 than 24 hours)

 -  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 MDE

 -  History of normal pressure hydrocephalus

 -  History of cancer metastatic to the central nervous system

 -  History of Parkinson's disease or other basal ganglia disease

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

 -  Inability to undergo an MRI scan

 -  History of DSM-IV Axis I Mood Disorder