Evidence map›Paper›PMID 27630617›Full record

ArticleFrontiers in endocrinology2016

The Ticking of the Epigenetic Clock: Antipsychotic Drugs in Old Age.

Adonis Sfera, Carolina Osorio, Luzmin Inderias, Michael Cummings

Open access · goldAbstract read
In one paragraph

Article in Frontiers in endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.1field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Adonis SferaPsychiatry, Patton State Hospital , Patton, CA , USA.
Carolina OsorioPsychiatry, Loma Linda University , Loma Linda, CA , USA.
Luzmin InderiasPsychiatry, Patton State Hospital , Patton, CA , USA.
Michael CummingsPsychiatry, Patton State Hospital , Patton, CA , USA.
Patton State Hospital · USLoma Linda University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear. CNS small vessel disease (SVD) is a well-known age-related risk factor for strokes, dementia, and sudden death, which may constitute the initial CVAE-predisposing pathology. Therefore, we propose the two strikes CVAE paradigm, in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities may be directly proportional with the CVAE risk. To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4). Since microRNA-29 has shown efficacy against the same malignancies and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 upregulation, which in turn facilitates the development of SVD.

aimTo assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.

methodWe conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity and may be relevant for CVAE.

conclusionUpregulated microRNA-29 silences the expression of 18 genes connected with capillary stability, engendering a major vulnerability for SVD (first strike) which in turn increases the risk for CVAE after exposure to APDs (second strike).

Indexed as

antipsychotic medicationsdiabetes mellitusmicroRNA-29SIRT-1strokeVEGF

Identifiers

PMID27630617
PMCPMC5005952
OpenAlexW2516084725

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.