OBJECTIVE: For over 25 years, it has been hypothesized that major
depression is due to a deficiency of available serotonin or subsensitivity
of key serotonin receptors in relevant brain regions. Direct evidence
supporting this hypothesis has been lacking because of the difficulty in
studying regional brain serotonergic function. The authors have developed a
method for visualizing in vivo regional brain responses to serotonin
release by comparing regional brain glucose metabolism after administration
of the serotonin-releasing drug dl- fenfluramine, relative to placebo.
METHOD: Results with healthy subjects (N = 6) were compared to those
obtained with drug-free inpatients with moderately severe major depression
(N = 6). RESULTS: Healthy subjects had several areas of statistically
significant increases in metabolism, mostly in the left prefrontal and
temporoparietal cortex, and areas of decreased metabolism, such as in the
right prefrontal cortex. In contrast, the depressed patients had no areas
of increase or decrease in metabolism, differing significantly from healthy
subjects. Results with patients resembled those with healthy subjects (N =
10) who were scanned twice without active drug on either occasion.
CONCLUSIONS: This study provides the first direct visualization of blunted
regional brain responses to serotonin release in the brain of patients with
major depression, a finding that supports the hypothesis of impaired
serotonergic transmission in depression.