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.
Highlights
With a lifetime prevalence of more than 10%, depression is among the most common mental disorders, thereby imposing a substantial personal, economic, and societal burden[1]
The concentrations of glial fibrillary acidic protein (GFAP) in the cerebellum, prefrontal cortex, and anterior cingulate cortex have been found to be lower in patients with depression than in healthy controls[11,12,13]
Rationale of this study The present study aimed to investigate the potential role of the microglial markers GFAP and S100B in the cerebrospinal fluid (CSF) of patients diagnosed with unipolar depression and compare their levels with those of a control group of participants with idiopathic intracranial hypertension (IIH, formerly termed pseudotumor cerebri)
Summary
With a lifetime prevalence of more than 10%, depression is among the most common mental disorders, thereby imposing a substantial personal, economic, and societal burden[1]. In recent years, an increasing number of studies have suggested that inflammatory processes may be responsible for depressive symptomatology[3,4,5,6,7,8,9,10]. Proteins in the S100 protein family can influence inflammatory processes They regulate a variety of cell types, such as astrocytes, lymphocytes, and smooth muscle cells[16]. Most studies that have examined these inflammatory markers in the context of major depression relied on serum or tissue samples. The concentration, origin, and role of inflammatory markers in the cerebrospinal fluid (CSF) of patients with depression have received considerably less attention in psychiatry (for an overview of previous studies see Table 1). CSF investigations are needed to better understand the potential role of these biomarkers in the central nervous system, as they can provide detailed insights into intrathecal processes
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