MicroRNA-195 predicts olanzapine response in drug-free patients with schizophrenia: A prospective cohort study

Abstract

Background: Disturbances of microRNA-195 have been implicated in the pathogenesis of schizophrenia. However, microRNA-195 levels in schizophrenia are controversial. Aims: To the best of our knowledge, this is the first study to examine microRNA-195 levels in untreated schizophrenia patients and their relationship to olanzapine response. Methods: We recruited 81 untreated schizophrenia patients and 96 healthy controls. The patients received 2 months olanzapine treatment. MicroRNA-195 levels in peripheral blood mononuclear cells were measured using quantitative real-time polymerase chain reaction testing. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale. Results: No significant differences in microRNA-195 levels were found between patients and healthy controls ( p > 0.05). Olanzapine significantly reduced microRNA-195 levels after 2 months treatment ( p = 0.003). Interestingly, microRNA-195 levels decreased significantly in responders ( p = 0.010), but not in non-responders ( p > 0.05). Both baseline microRNA-195 levels ( p = 0.027, p = 0.030) and the reduction rate of microRNA-195 levels ( p = 0.034, p = 0.044) were positively associated with the reduction rate of Positive and Negative Syndrome Scale total score and general psychopathological subscale score. Multiple stepwise regression analysis revealed that baseline microRNA-195 level was an independent contributor to the reduction in Positive and Negative Syndrome Scale total score and the general psychopathological subscale score ( p = 0.018, p = 0.030). Finally, logistic regression analysis suggested that baseline microRNA-195 level can serve as a biomarker for response to olanzapine ( p = 0.037). Conclusions: Our data indicate that microRNA-195 level may predict symptomatic improvement and olanzapine response in schizophrenia patients, suggesting that microRNA-195 should be considered as a potential therapeutic target for antipsychotics.

Research Progress on the Correlation Between Epigenetics and Schizophrenia

“…For instance, a previous study has revealed a significantly decreased level of miR-195 in peripheral blood mononuclear cells of patients responding to olanzapine treatment, although its level did not vary between drug-naïve schizophrenia patients and controls (Huang et al, 2021), and serum level of miR-21 was decreased following administration of antipsychotics (Chen S. D. et al, 2016). Moreover, both baseline level and reduction rate were positively correlated with reduction rate of positive and negative syndrome scale total scores (Huang et al, 2021). The function of lncRNAs has been appreciated in the pathogenesis of mental diseases including schizophrenia, bipolar disease, and depression, by dysregulating the expression of target genes, and some specific lncRNAs play an important role in the recovery of depressed patients with antidepressant therapy (Table 2).…”

“…Some of the miRNAs have been identified to be associated with treatment responsiveness and efficacy rather than the disease itself. For instance, a previous study has revealed a significantly decreased level of miR-195 in peripheral blood mononuclear cells of patients responding to olanzapine treatment, although its level did not vary between drug-naïve schizophrenia patients and controls ( Huang et al, 2021 ), and serum level of miR-21 was decreased following administration of antipsychotics ( Chen S. D. et al, 2016 ). Moreover, both baseline level and reduction rate were positively correlated with reduction rate of positive and negative syndrome scale total scores ( Huang et al, 2021 ).…”

Kynurenine pathway metabolites and therapeutic response to olanzapine in female patients with schizophrenia: A longitudinal study

“…At baseline and 4‐week follow‐up, PANSS was used to evaluate the severity of psychotic symptoms. The reduction rate in the PANSS score was calculated by the formula: ( T b − T a ) / T a × 100%, where T a is the score at baseline and T b is the score at follow‐up 38 . Patients were defined as responders when the reduction rate of the PANSS total score was more than 30% according to previous studies 39,40 …”

“…Nurses monitored adherence to olanzapine treatment. 38 Patients were defined as responders when the reduction rate of the PANSS total score was more than 30% according to previous studies. 39,40…”