Schizophrenia is characterized by disturbances originate in neuronal development and a subtle brain pathology in which deficits in specific GABAergic and glutamatergic neuronal subtypes are apparent. This is demonstrated by decreases in markers of GABAergic neuronal functions, such as expression of the synthesising enzyme glutamic acid decarboxylase (GAD) and parvalbumin (PV), a protein present in a subgroup of GABA-containing interneurons; and also in the glutamatergic dysfunction, mainly N-methyl D- aspartate receptors (NMDARs). Several animal paradigms, such as isolation rearing, sub-chronic PCP administration and neonatal inflammatory challenge, that model aspects of schizophrenia also result in deficits of PV and GAD67, indicative of GABAergic pathology underlying the abnormal behaviours in these models. In parallel, knockout and knockdown animals for NMDAR subunits, such as NR1 and NR2, exhibit behavioural changes similar those present in schizophrenia. Recent studies have demonstrated abnormalities in DNA methylation in various indicators of GABAergic and glutamatergic function in schizophrenia. These abnormalities include both indicators of a general hypermethylation in brain regions important in the pathology of the disease, and effects on specific components principally linked to GABAergic and glutamatergic neurons. These findings suggest that a hyperfunctional DNA methylation may be responsible for deficiencies in excitatory and inhibitory neurotransmissions. There is also evidence suggesting that such effects may be ameliorated by antipsychotic drug treatment. As yet, however, these effects have not been investigated in the animal models that mimic aspects of schizophrenia and in patients in first episode of psychosis. Thus, the aim of this work is to evaluate if there is a hypermethylation in the GABAergic and glutamatergic markers in brain tissue and peripheral blood from rats undergoing isolation rearing and in the peripheral blood of patients in first episode of psychosis, siblings and health controls.
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