Expression of BDNF-Associated lncRNAs in Treatment-Resistant Schizophrenia Patients

Abstract

Long non-coding RNAs (lncRNAs) play a decisive role in the development of the central nervous system and modulation, differentiation, and function of neurons. Thus, any abnormal pattern of expression of these transcripts might alter normal development leading to neuropsychiatric disorders. In this regard, transcripts of brain-derived neurotrophic factor (BDNF) and four BDNF-associated lncRNAs (BDNF-AS, MIR137HG, MIAT, and PNKY) were evaluated in the peripheral blood of schizophrenia (SCZ) patients as well as normal subjects. The results indicated that the relative expression (RE) of PNKY was higher in SCZ patients as compared with controls (posterior beta of RE = 2.605, P value = 0.006) and in female patients compared with female controls (posterior beta of RE = 2.831, P value < 0.0001). BDNF expression was also higher in SCZ patients when compared with controls (posterior beta of RE = 0.64, P value < 0.036). Finally, a correlation was detected between the disease status and gender in terms of BDNF-AS expression (P value = 0.026). An inverse correlation was also found between levels of PNKY and age in the control group (r = - 0.30, P value < 0.0001). Expressions of BDNF and all lncRNAs were correlated with each other in both patients and controls. PNKY had the best diagnostic power among all assessed genes in the identification of disease status (area under curve = 0.78). BDNF, BDNF-AS, MIR137HG, and MIAT genes could discriminate SCZ patients from normal subjects with diagnostic power of 71%, 72%, 67%, and 68%, respectively. The current investigation suggests the possibility of the application of transcript levels of lncRNAs as an SCZ diagnostic marker. However, it warrants further studies in larger sample sizes.

Keywords: BDNF; BDNF-AS; MIAT; MIR137HG; Schizophrenia; lncRNA.