Schizophrenia, genetics, epigenesis, environment: a systematic review of unifi ed etiological hypotheses and genetic profi le; and a new algorithm to cope with the main fi ndings
Esquizofrenia, genética, epigênesis, ambiente: uma revisão sistemática das hipóteses etiológicas unifi cadas e do perfi l genética; e um novo algoritmo para o tratamento dos achados principais
Machado Dias, Alvaro
Luiz Rodriguez, E. Avelino
Context: schizophrenia is a highly complex syndrome, related to genes, and to non-genetic risk factors. Famous epidemiological studies reported its presence among all cultures and geographic regions. In that sense, Unifi ed Etiological hypothesis face the challenge to both present experimental data, and to show that the fi ndings may cope with the syndrome’s universal profi le. Objectives: systematically review the most prominent Unifi ed Etiological hypothesis, as much as the semantic distribution of genetic fi ndings (under up to date data mining techniques), and propose a new model, based on the dynamic effects of epigenics over genetic activation in both neurodevelopment and early adulthood. Results: in general, Unifi ed Etiological Hypothesis contradict the main genetic fi ndings (which suggest that schizophrenias’ genes are mostly associated with neurotransmitter profi - les, like D-1 and the Glutamate-NMDA cascade); also in general, genetic fi ndings are spread all over the genome (as we reveal with a topological map of the 3519 studies on the matter). The key for this conundrum may be represented by the association between the perspective that each polymorphism associated with schizophrenia represents a statistical risk factor (e.g. increasing the risk of developmental instability) while epigenetic molecular cascades and environmental factors considerably infl uence this picture, affecting genetic activation within critical periods.