<p>Impact of Expression and Genetic Variation of microRNA-34b/c on Cognitive Dysfunction in Patients with Major Depressive Disorder</p>

Abstract

Background: Patients suffering from major depressive disorder (MDD) commonly demonstrate lower performance across multiple cognitive domains. Cognitive impairment is an intrinsic characteristic of MDD status and is often influenced by genetic factors. microRNAs (miRNAs or miRs) have been shown to have important implications in the etiology of MDD. Therefore, we aimed to identify and analyze the impact of expression and genetic variation of miR-34b/c on cognitive dysfunction in MDD. Methods: First, we analyzed miR-34c-5p expression in 48 cases of MDD and 54 healthy controls in a Chinese population using qRT-PCR. We assessed the relationship between the level of miR-34c-5p expression and cognitive performance by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test (TMT). Second, in order to characterize allelic effects of miR-34b/c on cognitive performance in MDD patients, we performed genetic association analysis of single-nucleotide polymorphism (SNP) loci of the MIR34B/C genes with cognitive function in a second group consisting of 531 MDD patients and 267 healthy controls. Results: We found a significant negative correlation between the level of miR-34c-5p expression and both the language and delayed memory index scores in patients with MDD. We also found a significant positive correlation between the level of miR-34c-5p expression and the time required to complete tests A and B of the TMT. The interaction between the rs2187473 genotype and the disease was significant for both immediate memory and delayed memory. In the patient group, the rs2187473 CC genotype was significantly associated with higher performance on immediate memory (F = 6.683, p < 0.05) and delayed memory tasks (F = 4.221, p < 0.05). Conclusion:Our findings suggest that changes in miR-34c expression level have important impacts on cognitive function in patients with MDD. In particular, the polymorphism rs2187473 is a potential genetic risk factor for cognitive function in MDD, which may be of clinical use.

The miRNome of Depression

“…Eight weeks of paroxetine and 12 weeks of escitalopram treatment normalized levels of miR-34a-5p in serum [ 111 ] and miR-34c-5p levels in whole blood [ 94 ]. Interestingly, the levels of blood miR-34c-5p were significantly negatively correlated with language and delayed memory index scores in MDD, but not healthy patients [ 152 ], which may suggest that alterations in the expression of the miR-34 family may contribute to decreased cognitive functions observed in depression.…”

Early-life stress induces genome-wide sex-dependent miRNA expression and correlation across limbic brain areas in rats

“…Regardless of sex, our data show a significant increase in PFC miR-20b-5p. A previous study showed that blood levels of miR-34c-5p decreased with improved cognitive and memory performance in depressed individuals [ 41 ]. Similarly, we found increased miR-34c-5p expression in MS animals.…”

MicroRNAs as Critical Biomarkers of Major Depressive Disorder: A Comprehensive Perspective

“…MiR-30 family seems also interesting now that certain polymorphic variants such as miR-30e increase MDD susceptibility and others are biomarkers of late life depression (miR-30d) and PSD (miR-30a-5p) [ 181 , 182 , 183 , 184 ]. We find more variants of susceptibility for miR-34: rs4938723/rs28757623 polymorphisms affecting miR-34b/c genes are potential risk factors for suffering from MDD; moreover, MiR-34a is differentially expressed in MDD, bipolar disorder and schizophrenia in the anterior cingulate cortex [ 70 , 185 , 186 , 187 , 188 ]. More specifically, some variations of miR-504, rs686, affecting DRD1 regulation, have been found associated with higher depression scales [ 76 , 189 ].…”

“…Certain polymorphisms in miR-34 are categorized as more severe and related to suicide idea and cognitive dysfunction. For example, the polymorphism rs2187473 affecting miR-34c is a potential genetic risk factor for cognitive decline in MDD, as well as peripheral blood leukocytes levels of miR-34b and miR-34c were related to suicide idea [ 188 ]. MiR-137 was found downregulated by 25% in postmortem prefrontal cortex of depressed patients with suicidal behavior but further prognostic proposals have not been yet exploited [ 198 ].…”