The primary goal of this single-blind, placebo-controlled, within-subjects, double-scan,
one-visit neuroimaging study is to examine the effects of the hypnotic zolpidem (Ambien®) in
individuals who are maintained on selective serotonin reuptake inhibitors (SSRIs) for the
treatment of major depressive disorder. Specifically, levels of the brain chemical GABA will
be examined in the anterior cingulate and thalamus, two brain regions that play important
roles in mediating some of the effects of depression and sleep-related drugs, respectively.
Depressed individuals typically have lower levels of GABA than the healthy population, and
antidepressant treatment has been shown to help normalize this neurochemical in conjunction
with improved mood. Given that individuals maintained on SSRIs often are prescribed
sedative/hypnotics to treat concurrent insomnia, understanding a possible neurochemical
interaction between them, whether beneficial or harmful, is important for informing
evidence-based treatment strategies to treat the co-morbid patient. Zolpidem's effects on
GABA in participants who are maintained on SSRIs will be compared to baseline GABA levels in
these individuals (i.e., following placebo administration). Two separate scanning sessions
lasting approximately 45-60 min each will take place within one single study visit in order
to obtain these measurements using proton magnetic resonance spectroscopy (1H MRS). This type
of neuroimaging is like an MRI in that it is non-invasive, but it permits us to obtain
information about chemicals in the brain. A secondary goal of this study is to compare the
subjective drug effects, or how individuals feel, following the intervention. These measures
will be used to determine the existence of brain-behavior relationships in order to assess
the extent to which modulating GABA with zolpidem has effects on mood states in depressed
participants. Collectively, this study will contribute to our understanding of how these
drugs exert their effects when one is administered in the presence of the other, and it will
demonstrate that imaging is an important tool for informing us about how drug effects in the
brain ultimately result in behavior.