Schizophrenia: neuroinflammation, neurodegeneration or neurodevelopment? A genetic overview

Abstract

Schizophrenia is a devastating mental illness and its etiology is still largely unknown. Several gene mapping studies suggest that schizophrenia is a complex disorder, with a cumulative impact of variable genetic effects coupled with environmental factors. There is evidence that schizophrenia could be a neurodegenerative, neuroinflammatory or neurodevelopmental disorder. Neuropsychological data indicate neurocognitive functions are relatively stable over time after illness onset, whereas morphological data indicate a degenerative process; potential roles of neuroinflammation in the etiology of psychiatric diseases including schizophrenia have also been suggested. Recent research indicates genetic overlap between schizophrenia and syndromes in which psychopathology manifests in childhood and that are often grouped together as 'neurodevelopmental disorders'. These findings challenge the etiological basis of current diagnostic categories and, together with evidence for frequent comorbidity, suggest that we should view the functional psychoses as members of a group that result in part from a combination of genetic and environmental effects on brain development and that are associated with specific and general impairments of cognitive function. The objective was to perform a systematic literature review of articles on genetics of schizophrenia relating to neurodegeneration, neuroinflammation and neurodevelopment. After proper filter, we included 40 studies and reviewed each finding and its relevance to the hypotheses. We can conclude that the evidence points to schizophrenia as a neurodevelopmental disease with the direct presence of factors related to neuroinflammation and neurodegeneration.Keywords: Schizophrenia/genetics; Neurodevelopmental disorders/ genetics; Pantothenate kinase-associated neurodegeneration/ genetics; Neurogenetic inflammation/genetics; Genetics.RESUMO: Esquizofrenia é uma doença mental debilitante e sua etiologia é, em sua maior parte, desconhecida. Alguns estudos de mapeamento genético sugerem que esquizofrenia é uma doença complexa, com impacto acumulativo de fatores genéticos variáveis associados a fatores ambientais. Há evidência de que a esquizofrenia poderia ser uma doença neurodegenerativa, neuroinflamatória ou do neurodesenvolvimento. Dados neuropsicológicos indicam que funções cognitivas são relativamente estáveis no decorrer do tempo após o início da doença, enquanto dados morfológicos indicam processos degenerativos; papéis importantes da neuroinflamação na etiologia de doenças psiquiátricas, incluindo esquizofrenia, também foram sugeridos. Pesquisas recentes indicam sobreposição entre esquizofrenia e síndromes cuja fisiopatologia se manifesta na infância e são em geral agrupadas como "doenças do neurodesenvolvimento". Estes achados desafiam a base etiológica das categorias atuais de diagnóstico e, juntamente com a evidência de comorbidade frequente, sugerem que devemos ver as psicoses como membros do grupo que resulta em parte da combinação de efeitos genéticos e ambientai...

Oxidative stress biomarkers in treatment-responsive and treatment-resistant schizophrenia patients

“…[9][10][11] Various factors may influence manifestation of symptoms and patient response to pharmacological treatment, including environmental, genetic, and biochemical conditions. 12 Oxidative stress, which is understood as an imbalance between pro-oxidant and antioxidant molecules, is associated with schizophrenia progression, as well as with the development of other neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. 11,[13][14][15] In this case, progression is stimulated by an increase in reactive oxygen species (ROS) production, decreased antioxidant defense, or a combination of the two.…”