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Editorial

The role of glutamate excitotoxicity and

neuroinflammation in depression and suicidal

behavior: focus on microglia cells

Gianluca Serafini , Zoltan Rihmer , Mario Amore 1
1
2
1 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry,
University of Genoa, 16126 Genova, Italy.
2 Department of Clinical and Theoretical Mental Health, Semmelweis University, H‑1085 Budapest, Hungary.

Major depressive disorder (MDD) is associated with a the immunological origin of major depression.
[9]
significant disability worldwide, relevant psychosocial Inflammatory mediators and oxidative stress may lead
impairment, and increased risk of suicidal behavior. to glutamate excitotoxicity playing a significant role in
[1]
Although multiple psychoactive compounds are now the pathogenesis of MDD. [10] Notably, immunological
available, more than 20% of MDD patients treated differences have been frequently observed in patients
[2]
with traditional antidepressant drugs do not with MDD and suicidal behavior.
benefit from complete recovery and are affected by
treatment-resistance. Traditional antidepressant Glial cells have been proposed as potential
[3]
medications may be ineffective and sometimes worsen candidate targets for both glutamatergic-and
depressive symptoms in a vulnerable subpopulation inflammatory-mediated alterations underlying MDD
of patients with subthreshold hypomanic symptoms and suicidal behavior. [11,12] Historically, glial cells
that may be better included in the bipolar spectrum may be grouped in astrocytes, oligodendrocytes, and
rather than MDD. [4] microglia.

The most recent years have been characterized by the Microglial cells derive from the immune system and
paradigm shift from the monoamine conceptualization of may be considered the immunologic sentinel cells of the
depression to neuroplasticity hypothesis mainly focused brain. As the activation of microglial cells was associated
on glutamatergic dysfunctions. There are consistent with the abnormal production of inflammatory
[5]
evidence reporting that abnormalities of glutamatergic mediators, [13,14] these cells have been proposed as
neurotransmission are common in depressed possible effectors of the abnormal immune response in
individuals. Specifically, N-methyl-D-aspartate MDD. They provide immunomodulatory functions, [15]
[6]
receptors (NMDAR) overactivation seems to play a and functionally support neural plasticity-processes. [9]
critical role in the pathogenesis of MDD as reducing
their functioning may be associated with mood recovery. Importantly, the abnormal activation of microglial
For instance, ketamine has been recently investigated for cells reflected long-lasting depression- and anxiety-like
its potential antidepressant effects and improvement of behavioral effects. [11] This has been also confirmed
[7]
suicidal ideation beyond the monoamine hypothesis. by the fact that minocycline with anti-inflammatory
[8]
properties and microglia inactivation is not only able to
In addition, the existence of abnormalities in reverse microglial alterations, [16] but is also associated
inflammatory processes in depressed patients suggests with antidepressant-like activity in rats exposed to
learned helplessness. [17]
Access this article online
Quick Response Code: Unfortunately, some of the existing studies supporting
Website: the link between abnormal glial activation and MDD/
www.nnjournal.net
suicidal behavior are limited by small sample size.

DOI: As an example, Bayer et al. [18] in a postmortem study
10.4103/2347-8659.157955 found elevated microglial cells in both frontal cortex
and hippocampus of 6 depressed and 14 psychotic

Corresponding Author: Dr. Gianluca Serafini, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics,
Maternal and Child Health, Section of Psychiatry, University of Genoa, IRCCS San Martino, Largo Rosanna Benzi 10,
16126 Genova, Italy. E‑mail: gianluca.serafini@unige.it

PB Neuroimmunol Neuroinflammation | Volume 2 | Issue 3 | July 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 3 | July 15, 2015 127