Special Issue "Glutamatergic System in the Treatment of Major Depression"

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Psychiatric Diseases".

Deadline for manuscript submissions: closed (31 August 2021).

Special Issue Editors

Dr. Carmine Tomasetti
E-Mail Website
Guest Editor
Department of Mental Health, Azienda Sanitaria Locale Teramo, 64100 Teramo, Italy
Interests: neuroscience; psychiatry; psychopharmacology; dopamine–glutamate interaction; translational psychiatry

Special Issue Information

Dear Colleagues,

Major depression represents a protean psychiatric illness with heterogeneous clinical manifestations and multiple comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of depressive disorders, the pharmacotherapies currently used to treat major depression are mainly based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression. However, approximately one third to half of patients respond partially or become refractory to monoamine-based treatments, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular glutamatergic neurotransmission. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamatergic synaptic plasticity—which is involved in cognitive functions—has been demonstrated to be involved in several psychiatric syndromes, including depression, via transsynaptic modulation of specific molecular substrates, such as mTOR, GSK3, postsynaptic scaffolding proteins, etc.

The aim of this issue is to encourage a discussion which is as thorough as possible about the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of major depression pathophysiogenesis, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment and prevent suicide (which is the most devastating depression outcome). Moreover, we would like to stimulate the acquirement of both new clinical and “neurobiological targeted” strategies, based on the glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorder therapy.

A lot of studies have been focusing on the involvement of the glutamatergic system in the therapeutic strategies against major depression, as well as suicide prevention. We would like to deepen cutting-edge research on NMDA receptor modulators (e.g., ketamine, esketamine, memantine, lanicemine), AMPA receptor modulators, metabotropic glutamate receptor modulators, and psychotherapeutic (e.g., CBT) and glutamate-based brain stimulation techniques (e.g., ECT, TMS).

We would like to solicit articles in which new glutamate-based treatments for major depression are described and future research avenues on glutamate-targeting strategies are suggested to by-pass the limiting step of monoamine-based classical treatments.

Dr. Domenico De Berardis
Dr. Carmine Tomasetti
Guest Editors

Manuscript Submission Information

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  • psychopharmacology
  • dopamine–glutamate interaction
  • emotions
  • affective dysregulation
  • suicide
  • psychiatry

Published Papers (1 paper)

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Therapeutic Potentials of Ketamine and Esketamine in Obsessive–Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature
Brain Sci. 2021, 11(7), 856; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11070856 - 27 Jun 2021
Cited by 3 | Viewed by 1529
The obsessive–compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive–compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, [...] Read more.
The obsessive–compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive–compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords (“ketamine” or “esketamine”) AND (“obsessive” OR “compulsive” OR “OCD” OR “SUD” OR “substance use disorder” OR “addiction” OR “craving” OR “eating” OR “anorexia”) NOT review NOT animal NOT “in vitro”, on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine’s use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness. Full article
(This article belongs to the Special Issue Glutamatergic System in the Treatment of Major Depression)
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