Misdiagnoses of psychiatric disorders and the utility of diagnostic microRNA biomarkers

Due to overlapping symptoms and similarities with other illnesses, misdiagnosis and inappropriate treatment of psychiatric disorders frequently occur. Objective laboratory-based biomarkers that can be measured in blood-based samples are urgently needed to support clinical decision making. We have performed literature searches for microRNA expression in whole blood, blood plasma, and blood serum of adult patients with schizophrenia, bipolar disorder, and major depressive disorder compared to healthy control subjects. Expression of miR-4743 in blood plasma of schizophrenia patients was upregulated compared to controls while in major depressive disorder patients miR-4743 expression in blood plasma was downregulated compared to controls. Bipolar disorder patients had upregulated expression of miR-125a-3p, −21–3p in whole blood compared to controls, while major depressive disorder patients had downregulated expression of miR-125, −21 in whole blood compared to controls. Measurement of the expression levels of these specific microRNAs in whole blood and blood plasma would enable schizophrenia patients to be differentiated from major depressive disorder patients, and for bipolar disorder patients to be distinguished from major depressive disorder patients, respectively. Bipolar disorder patients could also be differentiated from major depressive disorder patients by upregulation of miR-140–3p, −21–3p, −30d-5p, −330–5p, −378a-5p in whole blood and upregulation of miR-134, −19b-3p in blood plasma. Receiver operating curve analysis showed that miR-134 had fair diagnostic power to distinguish bipolar disorder patients from major depressive disorder patients. Also, bipolar disorder patients could be distinguished from patients with early- or late-onset schizophrenia by upregulation of miR-34a, −34b and downregulation of miR-137, −34c in blood plasma. Receiver operating curve analysis of miR-137, −34a and −34b showed that each had high diagnostic power to distinguish bipolar disorder patients from schizophrenia patients. Pairwise testing of specific microRNAs in which one microRNA has upregulated expression and the other microRNA has downregulated expression will provide a much more robust and significant method of comparison.