Objective: Objective of this study is to identify whether microRNAs could be potential biomarkers for major depressive disorder (MDD).
Method: The blood samples of 50 patients and 41 healthy controls were collected from individuals, who were admitted to Mersin University Teaching Hospital Psychiatry Department. To identify better diagnosis and eliminate deficiency of Hamilton Depression Rating Scale (HDRS) (such as higher scoring of somatic and sleep items), we used both HDRS and Montgomery-Åsberg Depression Rating Scale (which is focused on core symptoms of depression). For accurate phenotyping, patients who met diagnostic criteria for major depression according to DSM IV, made a HDRS score above 17, has no comorbid psychiatric and medical condition, never used psychiatric drugs before and didn't take any medication for 1 month prior to blood sample taking period included. Subtypes like psychotic, melancholic, anxious, seasonal and atypical were excluded. Control group was also consisted of individuals who have no history of psychiatric and chronic medical condition, didn't take any drugs for 1 month prior to blood sample taking period and made a HDRS score under 7. We identified microRNAs related with genes that have been shown to be expressed similary in both prefrontal cortex and peripheral blood. We hypothesized that some of these microRNAs should be expressed differentially between MDD patients and controls and could be a biomarker for MDD. Blood samples which were drawn into EDTA tubes were accomplished by centrifugation at 4000 rpm for 15 min for plasma separation. Supernatant of plasma was recovered and stored at -80°C until analysis. RNA was isolated using the High Pure miRNA Isolation Kit following the manufacturer's protocol. cDNA and preamplification protocols were obtained from the isolated plasma microRNAs. The BioMark™ 96.96 Dynamic Array for real-time qPCR was used to simultaneously quantify the expression of 372 microRNAs. Mann Whitney U test was used for statistical analysis.
Results: Mir320a was significantly down regulated and mir451a was significantly up regulated among MDD patients.
Conclusion: MicroRNAs are small non-coding 16-22 nucleotide long RNA transcripts and they usually point mRNA's to degrade and provide them from translation. To our current knowledge, it is the first study investigating microRNAs as potential biomarkers for MDD. We found mir320a down regulated between MDD group and controls. Mir320a is predicted to be related with lots of genes which include GRIN2A and DISC1. Previous studies showed that GRIN2A was upregulated in both MDD patients and suicidal patients. Down regulation of mir320a is predicted to be related with upregulation of GRIN2A. A genetic linkage study demonstrates DISC1 as a potential target for MDD. According to our findings and previous literature, plasma mir320a levels could be an indicator of GRIN2A related processes in prefrontal cortex of depressed patients. We found mir451a upregulated among depressed patients. A previous study showed that ketamine treatment reduced mir451a levels. In recent years ketamine is predicted to be one of the rapid acting potential antidepressant treatments. Based on acting mechanism of ketamine mir451 could be a marker for treatment response. Our study demonstrates the possibility of microRNAs as diagnostic and prognostic biomarkers for depression.