Desipramine for Improving Cellular Signaling and Decreasing Symptoms of Major Depression

MDD is a serious mental illness that can interfere with a person's ability to eat, sleep,
work, and enjoy activities that were once pleasurable. It is characterized by several
symptoms, including as the following: persistent sad, anxious, or "empty" mood; feelings of
hopelessness or pessimism; and feelings of guilt, worthlessness, or helplessness. The
receptor-G protein-adenylate cyclase enzyme complex (AC enzyme complex) is a major cell
signaling system in the brain, blood, and other tissues in the body. Changes in this
signaling system among blood cells have been observed in people with major depressive
disorder. Research has shown that treatment with the benzodiazepine alprazolam corrects the
signaling problem, and thereby improves symptoms of MDD. This study will determine whether
impairments in the AC enzyme complex exist among depressed individuals. This study will also
evaluate the effectiveness of desipramine, an antidepressant, in improving blood cell
signaling, and thereby decreasing symptoms of depression in people with major depressive
disorder.

Both healthy and depressed participants will be recruited for this study. All depressed
participants in this study will first be assessed for depression severity using the Hamilton
Depression Rating Scale. If eligible for the study, participants will be examined to
determine AC enzyme complex functioning in both platelets and mononuclear leukocytes. A
cohort of the depressed participants will be treated with desipramine. They will be examined
to determine the drug's effect on AC enzyme complex functioning, as well as its effect on
MDD symptoms, at Weeks 1, 4, and 6.

Inclusion Criteria:

- Clinical diagnosis of MDD (as defined by SCID [DSM III-R] and a score of at least 15
on the 21-item Hamilton Depression Scale)

- Able to swallow tablets, give urine and blood samples, and participate in periodic
evaluations during the study

- Healthy volunteers show no current Axis I or Axis II disorders and score less than 8
on the Hamilton Depression Scale

Exclusion Criteria:

- Use of any of the following medications within the 2 weeks prior to study entry:
psychoactive medication; aspirin; or nonsteroidal anti-inflammatory agents

- Any alcohol or drug abuse within the 6 months prior to study entry

- Any major medical disorder