Most clinical major depression responds to standard treatments (medication and
psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond
to these treatments and are referred to as treatment-resistant major depression (TRMD). New
treatments for TRMD are needed, and one promising line of research are drugs known as
N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our
group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD. This
application proposes to take the next important step in understanding how nitrous oxide
exerts its effects in the human brain by using state-of-the-art brain neuroimaging
(functional connectivity magnetic resonance imaging) in a group of non-depressed, healthy
volunteers and comparing the results to a group of TRMD patients.
This study involves exposing 20 non-depressed healthy participants and 20 TRMD participants
to nitrous oxide and a placebo gas, to compare their brain images before and after each of
the inhalation sessions. Sessions will be separated by at least one month to prevent
treatment effects from carrying over into the following session. All willing and eligible
subjects will undergo up to six functional connectivity MRI scans, and two inhalation
sessions. Functional imaging in the brain will allow us to trace the interconnections between
various parts of the brain, including those involved with emotion and depression.
Other procedures will involve screening materials to ensure safety of the participants before
beginning the study (i.e. no MRI scan contraindications) and that subjects meet eligibility
criteria to being in the targeted age range, depression/non-depressed state, neurological
disorder history, and no medication exclusions.