Controls: Not meet The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for major depressive disorder (MDD) by scoring ≤7 on the Hamilton Depression Rating Scale (HDRS), 17-item; Treatment-Resistant Major Depression (TRMD) patients: Must meet a ≥17 score on the HDRS.
Controls: Must not have any history of depression as determined by reported history and medical record review; TRMD: Documented (chart review) failure to respond to ≥3-4 adequate dose/duration antidepressant treatments; ≥1 in the current depressive episode.
Good command of the English language
You may not be if
Meets criteria for any DSM-IV Axis I diagnosis as documented in medical records and as determined by structured clinical interview (except MDD for the TRMD group)
Known primary neurological disorders or medical disorders including dementia, stroke, encephalopathy Parkinson's Disease, brain tumors, multiple sclerosis, seizure disorder, severe cardiac or pulmonary disease
Any central nervous system active medication as determined by study investigator
Any known disease affecting drug metabolism and excretion (e.g. renal or liver disease) as determined by study investigator
Left-handedness
Current use of psychotropic medications, antidepressants, or prescription or non-prescription drugs/herbals intended to treat depression or anxiety (control group only)
Any recent (within past 12 months) history of substance dependence or abuse, determined by reported history or urine drug screen
Ability to become pregnant and not using effective contraception
Contraindication against the use of nitrous oxide:
1. Pneumothorax
2. Bowel obstruction
3. Middle ear occlusion
4. Elevated intracranial pressure
5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
6. Pregnant patients
7. Breastfeeding women
Inability to provide informed consent
Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic).
