Page 123 - MEGIN Book Of Abstracts - 2023

Nugent, Allison C; Kadriu, Bashkim; Yuan, Peixiong; contributor. Third, increased (2S,6S;2R,6R)-HNK maxi-
Gould, Todd D; Park, Lawrence T; Zarate, Carlos A mum observed concentration (Cmax) was associated
with increased MEG gamma power. While contrary to
Section on the Neurobiology and Treatment of Mood Disor- preclinical observations and our a priori hypotheses,
ders, National Institute of Mental Health, National Institutes these exploratory results replicate those of a recently
of Health, Bethesda, MD, USA; National Institute on Aging, published study documenting a relationship between
National Institutes of Health, Baltimore, MD, USA; Clinical higher (2S,6S;2R,6R)-HNK concentrations and weaker
Pharmacokinetics Research Unit, Pharmacy Department, antidepressant response in humans and provide fur-
National Institutes of Health, Bethesda, MD, USA; Magneto- ther rationale for studying gamma power changes as
encephalography Core Facility, National Institute of Mental potential biomarkers of antidepressant response.
Health, National Institutes of Health, Bethesda, MD, USA; Vet-
erans Affairs Maryland Health Care System, Baltimore, MD, Neuropsychopharmacology: official publication of the
USA; Section on the Neurobiology and Treatment of Mood American College of Neuropsychopharmacology (2020),
Disorders, National Institute of Mental Health, National Insti- Vol. 45, No. 8 (32252062) (32 citations)
tutes of Health, Bethesda, MD, USA. [email protected]

ABSTRACT A single, subanesthetic dose of (R,S)- Magnetoencephalographic Correlates of Suicidal
ketamine (ketamine) exerts rapid and robust antide- Ideation in Major Depression (2020)
pressant effects. Several groups previously reported
that (2S,6S;2R,6R)-hydroxynorketamine (HNK) had Gilbert, Jessica R; Ballard, Elizabeth D; Galiano, Christina
antidepressant effects in rodents, and that (2R,6R)-HNK S; Nugent, Allison C; Zarate, Carlos A
increased cortical electroencephalographic gamma
power. This exploratory study examined the relation- Section on the Neurobiology and Treatment of Mood Disor-
ship between ketamine metabolites, clinical response, ders, National Institute of Mental Health, National Institutes
psychotomimetic symptoms, and gamma power of Health, Bethesda, Maryland. Electronic address: jessica.
changes in 34 individuals (ages 18-65) with treatment- [email protected]
resistant depression (TRD) who received a single
ketamine infusion (0.5 mg/kg) over 40 min. Plasma con- BACKGROUND Defining the neurobiological underpin-
centrations of ketamine, norketamine, and HNKs were nings of suicidal ideation (SI) is crucial to improving our
measured at 40, 80, 120, and 230 min and at 1, 2, and understanding of suicide. This study used magnetoen-
3 days post-infusion. Linear mixed models evaluated cephalographic gamma power as a surrogate marker
ketamine metabolites as mediators of antidepressant for population-level excitation-inhibition balance to
and psychotomimetic effects and their relationship to explore the underlying neurobiology of SI and depres-
resting-state whole-brain magnetoencephalography sion. In addition, effects of pharmacological interven-
(MEG) gamma power 6-9 h post-infusion. Three sa- tion with ketamine, which has been shown to rapidly
lient findings emerged. First, ketamine concentration reduce SI and depression, were assessed.
positively predicted distal antidepressant response at
Day 11 post-infusion, and an inverse relationship was METHODS Data were obtained from 29 drug-free pa-
observed between (2S,6S;2R,6R)-HNK concentration tients with major depressive disorder who participated
and antidepressant response at 3 and 7 days post- in an experiment comparing subanesthetic ketamine
infusion. Norketamine concentration was not associ- (0.5 mg/kg) with a placebo saline infusion. Magnetoen-
ated with antidepressant response. Second, ketamine, cephalographic recordings were collected at baseline
norketamine, and (2S,6S;2R,6R)-HNK concentrations and after ketamine and placebo infusions. During
at 40 min were positively associated with contem- scanning, patients rested with their eyes closed. SI and
poraneous psychotomimetic symptoms; post-hoc depression were assessed, and a linear mixed-effects
analysis revealed that ketamine was the predominant model was used to identify brain regions where gamma

 ontents  Index 102
C