Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective

Autor(es)

Antunes, Andre S. L. M. ; Reis-de-Oliveira, Guilherme ; Martins-de-Souza, Daniel

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. N/A, p. 14-pg., 2024-07-19.

Resumo

COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes. (AU)

• Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/01410-1 - Avaliação dos efeitos da clozapina em células do sistema imune
• Beneficiário: Guilherme Reis-De-Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 20/10282-7 - Explorando as bases moleculares da infecção por SARS-CoV-2 em modelos pré-clínicos neurais
• Beneficiário: Andre Saraiva Leao Marcelo Antunes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado