Ketamine and other glutamate receptor modulators for depression in adults

Caddy, Caroline; Amit, Ben H.; McCloud, Tayla; Rendell, Jennifer M; Furukawa, Toshi A; McShane, Rupert; Hawton, Keith; Cipriani, Andrea

doi:10.1002/14651858.cd011612.pub2

Cited by 110 publications

(77 citation statements)

References 150 publications

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“…Since mice deficient in the serotonin neurotransmitter showed reduced depression-like behavior and chronic administration of the SSRI fluoxetine lead to increased hippocampal neurogenesis [77], this may be a feasible medication to restore neurogenesis in adults. In preclinical and clinical studies a single treatment of the antidepressant ketamine has been sufficient to relieve depressive symptoms in adult patients and C57BL/6 mice previously exposed to chronic stress [78,79]. In humans, ketamine is known to relief symptoms in a very short period of time, but more investigation is needed to ameliorate or prevent associated side effects [79].…”

Section: Discussionmentioning

confidence: 99%

Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice

Criado‐Marrero

Sabbagh

Jones

et al. 2020

Cells

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Tau dysfunction is common in several neurodegenerative diseases including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Affective symptoms have often been associated with aberrant tau pathology and are commonly comorbid in patients with tauopathies, indicating a connection between tau functioning and mechanisms of depression. The current study investigated depression-like behavior in Mapt−/− mice, which contain a targeted deletion of the gene coding for tau. We show that 6-month Mapt−/− mice are resistant to depressive behaviors, as evidenced by decreased immobility time in the forced swim and tail suspension tests, as well as increased escape behavior in a learned helplessness task. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5-bromo-2-deoxyuridine (BrdU) labeling. We found that neurogenesis is increased in the dentate gyrus of 14-month-old Mapt−/− brains compared to wild type, providing a potential mechanism for their behavioral phenotypes. In addition to the hippocampus, an upregulation of proteins involved in neurogenesis was observed in the frontal cortex and amygdala of the Mapt−/− mice using proteomic mass spectrometry. All together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression.

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Section: Discussionmentioning

confidence: 99%

Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice

Criado‐Marrero

Sabbagh

Jones

et al. 2020

Cells

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“…The FSL also exhibits a dysfunctional regulation of glutamate transmission and has a reduction of both neuronal and glial glutamate receptors and transporters (Eriksson et al, 2012; Gomez-Galan et al, 2013). This is of relevance, given the accumulating evidence that suggests an aberrant glutamatergic signaling in humans with MDD (Sanacora et al, 2012) in combination with the promising role of novel antidepressant compounds that act as glutamate receptor modulators (Caddy et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3)in Vitro

Wei

Melas

Villaescusa

et al. 2016

IJNPPY

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Background:MicroRNAs (miRNAs) are small regulatory molecules that cause translational repression by base pairing with target mRNAs. Cumulative evidence suggests that changes in miRNA expression may in part underlie the pathophysiology and treatment of neuropsychiatric disorders, including major depressive disorder (MDD).Methods:A miRNA expression assay that can simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to guide mRNA target selection. Luciferase reporter assays were used to verify miRNA targets in vitro.Results:We identified 23 miRNAs that were downregulated in the PFC of the FSL model compared with controls. Interestingly, one of the identified miRNAs (miR-101b) is highly conserved between rat and human and was recently found to be downregulated in the PFC of depressed suicide subjects. Using a combination of in silico and in vitro analyses, we found that miR-101b targets the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3). Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated in the PFC of the FSL model.Conclusions:Besides providing a list of novel miRNAs associated with depression-like states, this preclinical study replicated the human association of miR-101 with depression. In addition, since one of the targets of miR-101b appears to be a glutamate transporter, our preclinical data support the hypothesis of a glutamatergic dysregulation being implicated in the etiology of depression.

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“…Most of the recent trials on ketamine did not compare the efficacy of ketamine with other standard antidepressants [29]. The Cochrane Collaboration conducted a systematic review of previous ketamine trials and concluded that there was a limited superiority of ketamine over placebos in treating mood disorders [35, 36]. Hence, ketamine was not recommended to be used as an antidepressant.…”

Section: Discussionmentioning

confidence: 99%

Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015

et al. 2017

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ObjectivesThere are multifaceted views on the use of ketamine, a potentially addictive substance, to treat mental health problems. The past 15 years have seen growing media coverage of ketamine for medical and other purposes. This study examined the print news media coverage of medical and other uses of ketamine in North America to determine orientations and trends over time.MethodsPrint newspaper coverage of ketamine from 2000 to 2015 was reviewed, resulting in 43 print news articles from 28 North American newspapers. A 55-item structured coding instrument was applied to assess news reports of ketamine. Items captured negative and positive aspects, therapeutic use of ketamine, and adverse side effects. Chi-squares tested for changes in trends over time.ResultsIn the 15-year reviewed period, the three most frequent themes related to ketamine were: abuse (68.2%), legal status (34.1%), and clinical use in anesthesia (31.8%). There was significant change in trends during two periods (2000–2007 and 2008–2015). In 2008–2015, print news media articles were significantly more likely to encourage clinical use of ketamine to treat depression (p = 0.002), to treat treatment resistant depression (p = 0.043), and to claim that ketamine is more effective than conventional antidepressants (p = 0.043).ConclusionsOur review found consistent positive changes in the portrayals of ketamine by the print news media as a therapeutic antidepressant that mirror the recent scientific publications. These changes in news media reporting might influence the popularity of ketamine use to treat clinical depression. Guidance is required for journalists on objective reporting of medical research findings, including limitations of current research evidence and potential risks of ketamine.

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Ketamine and other glutamate receptor modulators for depression in adults

Cited by 110 publications

References 150 publications

Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice

Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice

MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3)in Vitro

Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015

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