Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression

Abstract

Inflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p < 0.001). These results remained significant in a sub-analysis in which all controls were compared with patients suffering from depression matched 1:1 by age and sex (632.26 pg/ml vs. 245.56 pg/ml, p < 0.001). Levels of S100B did not differ significantly between patients and controls (1.06 ng/ml vs. 1.17 ng/ml, p = 0.385). GFAP levels correlated positively with albumin quotients (p < 0.050), S100B levels correlated positively with white blood cell counts (p = 0.001), total protein concentrations (p < 0.001), and albumin quotients (p = 0.001) in the CSF. The significance of the study is limited by its retrospective and open design, methodological aspects, and the control group with idiopathic intracranial hypertension. In conclusion, higher GFAP levels in patients with depression may be indicative of altered microglia activity, especially in astrocytes, in patients with unipolar depression. In addition, correlation analyses support the idea that S100B levels could be related to the integrity of the blood–brain/CSF barrier. Further multimodal and longitudinal studies are necessary to validate these findings and clarify the underlying biological processes.

The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium

“…Plasma GFAP levels are also elevated in individuals with neuropsychiatric illnesses who lack brain radiological abnormalities (Esnafoglu et al, 2017). Decreased GFAP expression has been observed in post-mortem cerebral tissues from patients with MDD (Michel et al, 2021; Rajkowska et al, 2018) and the expression of both GFAP mRNA and protein is decreased in astrocytes in the postmortem locus coeruleus of individuals with MDD (Chandley et al, 2013). GFAP mRNA is also decreased in the postmortem prefrontal cortex of depressed suicide victims (Nagy et al, 2015).…”

“…In addition to elevated levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), stimulated peripheral whole blood from individuals with MDD was shown to have an increased PDGF production (Rachayon et al, 2022). Patients with MDD have elevated CSF GFAP levels (Michel et al, 2021) and serum GFAP levels that may rise with increasing MDD severity (Steinacker et al, 2021). Plasma GFAP levels are also elevated in individuals with neuropsychiatric illnesses who lack brain radiological abnormalities (Esnafoglu et al, 2017).…”

“…Moreover, MDD patients have elevated cerebro-spinal fluid (CSF) levels of glial fibrillary acidic protein (GFAP) (Michel et al, 2021), an intermediate filament in the cytoskeleton of astrocytes that is involved in cell communication, cell structure, and astrocyte function (Maes, 2022; Nedergaard et al, 2003; Wang et al, 2017). GFAP expression is increased in response to CNS trauma and reactive astrogliosis, and GFAP may be translocated into the peripheral circulation through BBB disruption (Hol and Pekny, 2015; Yang and Wang, 2015).…”

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression

“…For example, a recent preclinical study reported that 6 weeks of CUS followed by another 6 weeks of social isolation induced an increase in the number of GFAP + cells in the DG (Du Preez et al, 2021). Moreover, Michel et al (2021) found that the level of GFAP was significantly higher in patients with unipolar depression than in mentally healthy controls with idiopathic intracranial hypertension. Hence, both the loss and increase of astrocytes may be responsible for stressinduced depressive behavior.…”

Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders

“…The exclusion criteria for the control group were as follows: secondary forms of intracranial hypertension and psychiatric or other neurological disorders (except headaches). The control group was already published in earlier articles [ 27 , 31 , 39 , 40 ].…”