Glial fibrillary acidic protein as blood biomarker for differential diagnosis and severity of major depressive disorder

Steinacker, Petra; Shweiki, Mhd Rami Al; Oeckl, Patrick; Graf, Heiko; Ludolph, Albert C.; Schönfeldt‐Lecuona, Carlos; Otto, Markus

doi:10.1016/j.jpsychires.2021.09.012

Cited by 53 publications

(30 citation statements)

References 22 publications

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“…In this investigation, patient age positively related to serum GFAP levels, which is in accordance with recent findings in depressive disorders, 33 possible reflecting ‘normal’ neurodegenerative glial damage upon ageing. A recent study investigating human brains found age‐related decline of synaptic transmission and increased expression of GFAP in both sexes 34 .…”

Section: Discussionsupporting

confidence: 92%

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

et al. 2022

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Aims Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF. Methods and resultsUsing bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = À4.7; P < 0.001), alanine aminotransferase (T = À2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = À3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025). Conclusions Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

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Section: Discussionsupporting

confidence: 92%

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

et al. 2022

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…Second, serum GFAP has been advocated as a marker to monitor astroglial pathology, including during the course of MDD (Al Shweiki et al, 2017; Hol and Pekny, 2015; Steinacker et al, 2021). CSF levels of GFAP may reflect astrocytic changes, and in neurodegenerative diseases, serum GFAP has been suggested to constitute a diagnostic or monitoring biomarker (Abu-Rumeileh et al, 2019; Oeckl et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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

Al‐Hakeim

Al-Naqeeb

Almulla

et al. 2022

Preprint

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Background. Major depressive disorder (MDD) is characterized by elevated activity of peripheral neuro-immune and neuro-oxidative pathways, which may cause neuro-affective toxicity by disrupting neuronal circuits in the brain. No study has explored peripheral indicators of neuroaxis damage in MDD in relation to serum inflammatory and insulin resistance (IR) biomarkers, calcium, and the physio-affective phenome consisting of depressive, anxious, chronic fatigue, and physiosomatic symptoms. Methods. Serum levels of phosphorylated tau protein 217 (P-tau217), platelet-derived growth factor receptor beta (PDGFR), neurofilament light chain (NF-L), glial fibrillary acidic protein (GFAP), C-reactive protein (CRP), calcium and the HOMA2-insulin resistance (IR) index were measured in 94 MDD patients and 47 controls. Results. 61.1% of the variance in the physio-affective phenome (conceptualized as a factor extracted from depression, anxiety, fatigue and physiosomatic symptoms) is explained by the regression on GFAP, NF-L, P-tau2017, PDGFRβ and HOMA2-IR (all positively associated), and decreased calcium. In addition, CRP and HOMA2-IR predicted 28.9% of the variance in the neuroaxis index. We observed significant indirect effects of CRP and calcium on the physio-affective phenome which were partly mediated by the four neuroaxis biomarkers. Annotation and enrichment analysis revealed that the enlarged GFAP, P-tau217, PDGFR, and NF-L network was enriched in glial cell and neuronal projections, the cytoskeleton and axonal transport, including a mitochondrion. Conclusions: Peripheral inflammation and IR may damage the astroglial and neuronal projections thereby interfering with mitochondrial transport. This toxicity, combined with inflammation, IR and lowered calcium, may, at least in part, induce the phenome of MDD.

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“…Several additional inflammatory factors, such as specific chemokines (MCP-1, fractalkine), glial factors (GFAP, S100B), or lipid-derived mediators such as endocannabinoids, and neurodegeneration-related molecules such as neurofilament light chain, neurogranin and β-amyloid peptide isoforms (Aβ42, Aβ40, Aβ38) and their fragments could be promising biomarkers in patients with BD in relation to prospective clinical outcomes, such as those of neuronal injury, cognitive deficits and risk of dementia [ 93 ]. Recent studies have also evaluated non-coding RNA expression, sexual hormones, oxidative stress (uric acid, bilirubin, albumin) and metabolic biomarkers (metabolic syndrome, overweight/obesity, thyroid and liver function) in predicting BD and suicidality in individuals with bipolar disorder [ 94 , 95 , 96 , 97 , 98 ]. In addition, big data of cerebral blood flow and structural and functional connectivity using magnetic resonance imaging are becoming useful tools for actual practice in psychiatry [ 99 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

et al. 2022

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Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = −0.22, Confidence Interval 95% = −0.38, −0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.

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Glial fibrillary acidic protein as blood biomarker for differential diagnosis and severity of major depressive disorder

Cited by 53 publications

References 22 publications

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

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

Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

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