Role of tissue plasminogen activator and plasminogen activator inhibitor as potential biomarkers in psychosis

Elmi, Sarah; Sahu, Geetanjali; Malavade, Kishor; Jacob, Theresa

doi:10.1016/j.ajp.2019.05.021

Cited by 14 publications

(5 citation statements)

References 42 publications

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“…PAI-1 is secreted from endothelial cells and reduces the activity of tPA, playing a negative role in the formation of BDNF [22]. Although some studies found a decrease of PAI-1 in SZ patients, other studies did not nd a signi cant difference compared to HC [37]. In the current study, tPA levels were found to be signi cantly lower in the UAS compared to the other two groups.…”

Section: Discussioncontrasting

confidence: 61%

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?

et al. 2022

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Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that the siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which is tpa-BDNF pathways proteins and thought to play a role in synaptic pruning as a possible endophenotype of schizophrenia. Forty drug-naïve patients with rst-episode psychosis (FEP) matched for age, gender and level of education, 40 unaffected siblings (UAS) of patients with FEP and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway, pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiateFEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the healthy control group with statistically signi cant differences between all 3 groups. The plasma levels of pro-BDNF in the healthy control group were similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data Support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ, and this imbalance could be an endophenotype of the disease.

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Section: Discussioncontrasting

confidence: 61%

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?

et al. 2022

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“…The only study based on gold standard methods did not find any patient positive for anti-GluN1 IgG [ 256 ]. Studies have shown that SCZ patients have lower tPA and higher PAI-1 levels than the general population [ 257 ]. In the psychiatric field, the link between psychotic disorders, particularly SCZ and immune system dysregulations, including autoimmunity, is a concept that regained strong support thanks to the better characterization of inflammatory-induced psychotic symptoms and autoimmune encephalitis, the most well characterized of which is anti-NMDAR encephalitis [ 258 ].…”

Section: Cns Diseases and Nmdar Dysfunctionsmentioning

confidence: 99%

Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases

Seillier

Lesept

Toutirais

et al. 2022

IJMS

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The excitatory neurotransmission of the central nervous system (CNS) mainly involves glutamate and its receptors, especially N-methyl-D-Aspartate receptors (NMDARs). These receptors have been extensively described on neurons and, more recently, also on other cell types. Nowadays, the study of their differential expression and function is taking a growing place in preclinical and clinical research. The diversity of NMDAR subtypes and their signaling pathways give rise to pleiotropic functions such as brain development, neuronal plasticity, maturation along with excitotoxicity, blood-brain barrier integrity, and inflammation. NMDARs have thus emerged as key targets for the treatment of neurological disorders. By their large extracellular regions and complex intracellular structures, NMDARs are modulated by a variety of endogenous and pharmacological compounds. Here, we will present an overview of NMDAR functions on neurons and other important cell types involved in the pathophysiology of neurodegenerative, neurovascular, mental, autoimmune, and neurodevelopmental diseases. We will then discuss past and future development of NMDAR targeting drugs, including innovative and promising new approaches.

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“…In support of this suggestion, FES patients showed a higher PAI-1/tPA ratio. 18 Indeed, elevated PAI-1 is considered a risk factor for thrombosis and atherosclerosis, whereas PAI-1/tPA ratio has been used as an index of abnormalities in thrombosis/fibrinolysis system. 19 Along with elevated PAI-1, circulating level of sP-sel in FES patients in this study was also higher than healthy controls, indicating platelet and endothelial cell activation.…”

Section: Discussionmentioning

confidence: 99%

Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications

Zheng,

Liu,

et al. 2023

Therapeutic Advances in Psychopharmacology

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Background: Previous studies reported higher incidences of venous thromboembolism and cardiovascular disease in schizophrenia patients and higher indicators of thrombosis, thrombocyte activation, and platelet dysfunction. Objectives: To check if first-episode schizophrenia (FES) patients have a hypercoagulable state and determine whether acute and chronic antipsychotics have the same effect on blood coagulation or fibrinolysis-related biomarkers. Design: Case-control study. Methods: A total of 81 participants were grouped in FES, chronic schizophrenia (CS), and healthy controls (HCs). In addition to demographic data and clinical characteristics, immunological analyses were performed to measure plasma levels of D-dimer, plasminogen activator inhibitor-1 (PAI-1), soluble P selectin (sP-sel), tissue plasminogen activator (tPA), thrombotic precursor protein (TpP), and von Willebrand’s disease factor (vWF). Results: Compared to HC group, FES patients showed higher PAI-1 (28.61 ng/ml versus 15.69 ng/ml), sP-sel (2.78 ng/ml versus 1.18 ng/ml), and TpP (15.61 µg/ml versus 5.59 µg/ml) along with a higher PAI-1/tPA (3.12 versus 2.00). Acute antipsychotic medication reduced higher PAI-1 (28.61 → 21.99), sP-sel (2.78 → 1.87), tPA (9.59 → 5.83), TpP (15.61 → 10.54), and vWF (383.18 → 291.08) in FES patients. However, plasma sP-sel and vWF in CS patients returned to the pre-treatment levels in FES patients, and PAI-1/tPA significantly decreased compared to FES patients. Conclusion: These results suggest a hypercoagulable state in FES patients and demonstrate contrast effects of acute and chronic antipsychotics on coagulation or fibrinolysis in schizophrenia patients.

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Role of tissue plasminogen activator and plasminogen activator inhibitor as potential biomarkers in psychosis

Cited by 14 publications

References 42 publications

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the “Beware the Ides of March” for Unaffected Relatives of Schizophrenia Patients?

Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases

Hypercoagulable state in patients with schizophrenia: different effects of acute and chronic antipsychotic medications

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