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DNA methylation in cocaine use disorder–An epigenome-wide approach in the human prefrontal cortex

Overview of attention for article published in Frontiers in Psychiatry, February 2023
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  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#23 of 12,832)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

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40 news outlets
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6 blogs
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1173 X users

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4 Dimensions

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12 Mendeley
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Title
DNA methylation in cocaine use disorder–An epigenome-wide approach in the human prefrontal cortex
Published in
Frontiers in Psychiatry, February 2023
DOI 10.3389/fpsyt.2023.1075250
Pubmed ID
Authors

Eric Poisel, Lea Zillich, Fabian Streit, Josef Frank, Marion M. Friske, Jerome C. Foo, Naguib Mechawar, Gustavo Turecki, Anita C. Hansson, Markus M. Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H. Witt

Abstract

BackgroundCocaine use disorder (CUD) is characterized by a loss of control over cocaine intake and is associated with structural, functional, and molecular alterations in the human brain. At the molecular level, epigenetic alterations are hypothesized to contribute to the higher-level functional and structural brain changes observed in CUD. Most evidence of cocaine-associated epigenetic changes comes from animal studies while only a few studies have been performed using human tissue.MethodsWe investigated epigenome-wide DNA methylation (DNAm) signatures of CUD in human post-mortem brain tissue of Brodmann area 9 (BA9). A total of N = 42 BA9 brain samples were obtained from N = 21 individuals with CUD and N = 21 individuals without a CUD diagnosis. We performed an epigenome-wide association study (EWAS) and analyzed CUD-associated differentially methylated regions (DMRs). To assess the functional role of CUD-associated differential methylation, we performed Gene Ontology (GO) enrichment analyses and characterized co-methylation networks using a weighted correlation network analysis. We further investigated epigenetic age in CUD using epigenetic clocks for the assessment of biological age.ResultsWhile no cytosine-phosphate-guanine (CpG) site was associated with CUD at epigenome-wide significance in BA9, we detected a total of 20 CUD-associated DMRs. After annotation of DMRs to genes, we identified Neuropeptide FF Receptor 2 (NPFFR2) and Kalirin RhoGEF Kinase (KALRN) for which a previous role in the behavioral response to cocaine in rodents is known. Three of the four identified CUD-associated co-methylation modules were functionally related to neurotransmission and neuroplasticity. Protein-protein interaction (PPI) networks derived from module hub genes revealed several addiction-related genes as highly connected nodes such as Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1), and Jun Proto-Oncogene, AP-1 Transcription Factor Subunit (JUN). In BA9, we observed a trend toward epigenetic age acceleration (EAA) in individuals with CUD remaining stable even after adjustment for covariates.ConclusionResults from our study highlight that CUD is associated with epigenome-wide differences in DNAm levels in BA9 particularly related to synaptic signaling and neuroplasticity. This supports findings from previous studies that report on the strong impact of cocaine on neurocircuits in the human prefrontal cortex (PFC). Further studies are needed to follow up on the role of epigenetic alterations in CUD focusing on the integration of epigenetic signatures with transcriptomic and proteomic data.

X Demographics

X Demographics

The data shown below were collected from the profiles of 1,173 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 12 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 2 17%
Professor > Associate Professor 1 8%
Researcher 1 8%
Student > Postgraduate 1 8%
Unknown 7 58%
Readers by discipline Count As %
Agricultural and Biological Sciences 2 17%
Biochemistry, Genetics and Molecular Biology 1 8%
Nursing and Health Professions 1 8%
Psychology 1 8%
Unknown 7 58%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 560. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 July 2023.
All research outputs
#43,125
of 25,571,620 outputs
Outputs from Frontiers in Psychiatry
#23
of 12,832 outputs
Outputs of similar age
#1,221
of 491,688 outputs
Outputs of similar age from Frontiers in Psychiatry
#3
of 688 outputs
Altmetric has tracked 25,571,620 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,832 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 491,688 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 688 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.