Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective.
Bianca Bianciardi, Helena Mastek, Michelle Franka, Peter J Uhlhaas
Schizophrenia Bulletin August 27, 2024 DOI: 10.1093/schbul/sbae090 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Intervention | NMDA-R antagonists |
| Topics | Ketamine |
| Keywords | E/i imbalance EEG/Meg Mk-801 Nmda-r antagonists Pcp Auditory perception Gamma-band oscillations Preclinical research Schizophrenia research Brain wave patterns Auditory processing Nmda receptors |
| Citations | 6 |
| Key findings | NMDA receptor antagonists partially recreate reductions in auditory gamma-band spectral power and intertrial phase coherence seen in schizophrenia. |
Abstract
N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity. This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power. Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients. Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cites 12
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
- Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia JAMA Network Open May 1, 2020
- Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine Neuropsychopharmacology February 6, 2019
and 7 more in the library