Alterations in the levels of an H1 DNA linker histone subtype in peripheral blood leukocytes from schizophrenia patients are linked with this disorder

AbstractSchizophrenia is an illness with severe social and familial impact. However, biomarkers related to chromatin that could help prognosis so as to prevent or attenuate the symptoms of first episodes and relapses of this malady  are either few or obscurely related. To this end, we decided to  analyze the chromatin constitution of certain  H1 DNA linker histone subtypes of schizophrenia patients, since this particular epigenetic chromatin parameter has not been previously studied with respect to this disorder. We examined the abundance of three histone H1 subtypes (also called variants), i.e., H1.0, H1.3, and H1.5, as well as the total histone H1 fraction in peripheral blood lymphocytes and neutrophils of hospitalized relapsed schizophrenic patients (inpatients), chronic outpatients on medication, first-episode patients, and normal control subjects. Of the three H1 subtypes  analyzed, H1.0 protein levels were found to be significantly lower in both lymphocytes and neutrophils of all patients that participated in the study. Total histone H1 levels were also found to be decreased in all patient cases. The fact that the changes in H1.0 levels and the total H1 fraction were observed regardless of state or phase of the disorder or the administered medication implies that these epigenetic changes are most probably intrinsically associated with the etiology of the illness. Due to the importance of the histone epigenetic profile in chromatin remodeling and gene expression, the observed non physiologiocal alterations of H1.0 levels and total H1 may contribute to the psychopathology of schizophrenia  by affecting the normal expression levels of certain genes. As this is the first time that a specific histone subtype is linked to schizophrenia, our work may serve as the basis for studying this disorder from a novel perspective, encompassing chromatin epigenetic research related to the histone protein subtypes/variants and as a novel source of biomarkers for this disorder