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Neuroinflammation as a cause of depression
Ketamine can help reverse Neuroinflammation – this may decrease depression
Evidence of Neuroinflammation in Fibromyalgia
Anthony L. Komaroff, MD reviewing
The degree of glial activation in the cortex correlated with reported intensity of patients’ fatigue.
A disorder, known as fibromyalgia, characterized by fatigue and pain, has long frustrated clinicians because conventional diagnostic testing reveals little evidence of objective pathology. In a new study from Boston and Stockholm, researchers used positron emission tomography (PET) to assess neuroinflammation in the brains of fibromyalgia patients.
The teams conducted PET scans in 31 fibromyalgia patients and 27 age- and sex-matched healthy controls. In fibromyalgia patients, the scans revealed widespread activation of glial cells (antigen-presenting cells) in the cortex, particularly in the frontal and parietal lobes. This glial activation was not seen in controls. Moreover, the degree of glial activation correlated with reported intensity of patients’ fatigue: the greater the neuroinflammation, the greater the fatigue (although not the pain).
Previous research has shown elevated levels of proinflammatory cytokines in the cerebrospinal fluid of patients with fibromyalgia. Interestingly, PET also has identified neuroinflammation in patients with a clinically similar condition, chronic fatigue syndrome. The current study provides direct evidence of neuroinflammation and suggests that neuroinflammation is a target for therapy. Indeed, one agent — low-dose naltrexone — reduced glial activation in the brain and improved symptoms in small controlled studies of fibromyalgia patients. The current study indicates that smoldering and potentially treatable neuroinflammation is present in the brains of patients with fibromyalgia.
Albrecht DS et al. Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation. Brain Behav Immun 2019 Jan; 75:72. (https://doi.org/10.1016/j.bbi.2018.09.018
Although pain is frequently accompanied with depression, little is known about the risk factors
contributing to individual differences to the comorbidity of pain and depression. In this study, we
examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the
individual differences in the development of neuropathic pain-induced depression. Rats were randomly
subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups
by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed
higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, IL-6) as well as imbalance of
pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and shamoperated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose
of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype.
Interestingly, higher serum levels of IL-1β and IL-6 in the rat with depression-like phenotype were
normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory
cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum
cytokines may be predictable biomarkers for ketamine’s antidepressant actions.
Mounting evidence suggests that activation of microglia and inflammatory response play an
important role in the pathogenesis of depression. A single or repeated sub-anesthetic dose
of ketamine administration induced fast and potent antidepressant effect. We investigated
the effect of ketamine on microglia activation and pro-inflammatory cytokines levels in
hippocampus of depression-like rats. Ketamine’s antidepressant effect on depression-like rats is accompanied by the inhibition of
microglia activation and pro-inflammatory cytokines levels in the hippocampus. Ketamine can
inhibit microglia activation stimulated by lipopolysaccharide (LPS) and pulmonary inflammatory responses induced by sepsis
[7,8]. However, whether the microglia deactivation and anti-inflammatory cytokines mediate ketamine’s antidepressant
effect is unclear. In our study, sub-anesthetic dose of ketamine administration for 7 consecutive days showed remarkable relief of behavioral changes induced by CUMS exposure, and was associated with the inhibition ofmicroglia and pro-inflammatory cytokinesin hippocampus, and it has been reported that ketamine may decrease the levels of
inflammation cytokines in sepsis patient. , inhibit the activation of microglia and the levels of inflammation cytokines in
cells induced by lipopolysaccharide (LPS)[7,8]. The mechanism may be that the proinflammation cytokines induced indoleamine2, 3-dioxygenase (IDO) activation (thelimited enzyme in kynurenine pathway),further activated kynurenine pathway to produce neuroactive metabolites and disturb the homeostasis between monoamine and glutamate neurotransmitter, which plays a key role in the pathogenesis of depression .