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Increased brain-derived neurotrophic factor exon IV histone 3 lysine 9 dimethylation in patients with schizophrenia

Background: Studies have mentioned that mixed-lineage leukemia 1 (MLL1) and histone 3 lysine 4 trimethylation (H3K4me3) of brain-derived neurotrophic factor (BDNF) exon IV from the postmortem brain tissue of patients with schizophrenia are related to the psychopathology of schizophrenia. We intended to investigate the levels of MLL1 messenger RNA (mRNA) and BDNF exon IV histone H3K9me2 and K27me3 in peripheral blood of patients with schizophrenia and healthy controls and to evaluate the relationships between aforementioned biomarkers and patients with/without clozapine treatment. Methods: During a one-year period, we recruited 36 patients with schizophrenia and 32 healthy controls. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). We sampled 10 mL of peripheral blood from each participant to analyze the MLL1 mRNA and BDNF exon IV H3K9me2 and K27me3 levels. Results: Significantly higher blood H3K9me2 (p < 0.01) levels were observed in patients with schizophrenia than those in healthy controls. However, no significant difference was found in H3K27me3 levels between patients with schizophrenia and controls. PANSS scores had significant correlations with H3K9me2 levels (p < 0.01). No significant differences were found in MLL1 mRNA levels, H3K9me2 levels, and H3K27me3 levels between patients with clozapine treatment and nonclozapine treatment. Conclusion: Blood BDNF exon IV H3K9me2 levels may be involved in the psychopathology of schizophrenia. More knowledge is needed before we can develop it to be a biomarker for schizophrenia.