Role of copper in depression. Relationship with ketamine treatment.
Jakub Słupski, Wiesław Jerzy Cubała, Natalia Górska, Maria Gałuszko‐węgielnik, Mariusz Stanisław Wiglusz
Medical Hypotheses October 2018 DOI: 10.1016/j.mehy.2018.07.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Ketamine Esketamine |
| Keywords | Copper Nmda |
| Key findings | Argues that copper ions interact with NMDAR and AMPA receptors to protect neurons from glutamatergic excitotoxicity, and that this interaction may be relevant to depression treatment. Proposes that measuring serum copper levels in patients treated with the NMDAR antagonist ketamine could reveal connections between NMDAR-targeting agents and trace elements, and calls for further research. |
Abstract
Depression is one of the most common psychiatric issues with a proportion of adults with major depressive disorder who fail to achieve remission with index pharmacological treatment. There are unmet needs in ADT focus on non-monoaminergic agents. Accumulating evidence suggests that the N-Methyl-d-aspartate receptor (NMDAR) plays an important role in the neurobiology and treatment of major depressive disorder. The role of copper ions in pathogenesis and treatment of depression is not fully clarified, however interaction between copper and NMDAR is of prime importance. Release of copper ions inhibits NMDAR and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor function thus protects neurons from glutamatergic excitotoxity. Abnormalities in glutamatergic transmission are the key of glutamate hypothesis of depression. Some authors revealed that NMDARs are also regulated by cellular prion protein (PrPC) and indicated that interactions of copper, glycine and NMDARs subunits are vital for the regulation of the receptor. As NMDAR antagonist ketamine is known to produce rapid antidepressive effect, observation of copper serum levels in patients treated with ketamine may provide important information about connections between NMDAR antagonistic agents and trace elements antagonistic to that receptor. It is necessary to carry out further studies related to copper and ketamine in depression treatment.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cites 7
- Ketamine use: a review Addiction July 21, 2011
- Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. Drug Discovery Today February 6, 2016
- Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic Journal of Psychopharmacology June 1, 2014
- NMDA Receptor Blockade at Rest Triggers Rapid Behavioural Antidepressant Responses Nature June 15, 2011
- A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. The International Journal of Neuropsychopharmacology May 5, 2011
and 2 more in the library