Association of circulating let-7b-5p with major depressive disorder: a nested case-control study

Abstract

Background Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD. Methods In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women’s Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression. Results Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12–0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2–5 years from baseline). Conclusions These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD.

Extracellular vesicles from cerebrospinal fluid revealed changes in miR‐19a‐3p and miR‐4516 expression in Slovene male suicides

“…Similar results were shown also in the hippocampus of the depressed mouse models 56 . However, one study on blood plasma of MDD subjects did not show any difference miR‐17‐5p expression 57 . Expression of miR‐4286 was studied in two brain regions, Brodmann area 24 of subjects with bipolar disorder died because of suicide, and Brodmann area 10 in suicides.…”

Serum microRNAs associated with concussion in football players

“…In this study, miRNA pair analysis confirmed the importance of miR-181c-5p expression combined with the expression levels of miR-338-3p or Let-7-5p in discriminating concussed from non-concussed players ( Figure 4 ). Interestingly, and of considerable diagnostic interest in the long-term development of brain degeneration, was the observation of a selective increase of a neurodegeneration-associated Let-7c-5p ( Figure 1A ), a chromosome-21q21-encoded miRNA also known to be specifically upregulated in Downs syndrome (trisomy 21) ( 67 , 68 ), AD ( 69 , 70 ) and depression ( 71 , 72 ). The selective upregulation of this specific miRNA may be related to and predictive for the initial triggering of brain damage and the onset of neurodegeneration characteristic of both acute and chronic brain injury as evidenced by TBI and AD.…”

“…Of interest, this miRNA signature suggests long-lasting molecular changes potentially associated with pathological behaviors that could also be explored in follow-up longitudinal studies. The upregulation of the Let-7c-5p miRNA may be a useful biomarker related to and predictive of the initial triggering of brain damage and the onset of neurological deficits in acute and chronic neurodegeneration as evidenced by concussive brain injury, TBI, Down's syndrome, AD, and psychiatric disorders ( 67 – 72 ). At the same time, miR-17-5p and miR-22-3p may be useful biomarkers for persistent neuronal injury from mTBI.…”

A systematic mini-review of epigenetic mechanisms associated with electroconvulsive therapy in humans

“…The most relevant considering statistical significance thresholds and longitudinal changes pre- and post-ECT treatment are miR-126, miR-106a, and miR-24. These 3 miRNAs have already been associated with depressive disorders, by evidence showing altered levels in peripheral blood samples of patients with MDD ( Camkurt et al, 2020 ; Maffioletti et al, 2021 ; Roumans et al, 2021 ). It seems that ECT treatment response is associated with a pattern of normalization of their expression in blood samples, which are altered by MDD in the pre-ECT period.…”