Evidence map›Paper›PMID 37674018›Full record

ArticleMolecular psychiatry2023

Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.

Stephanie Puig, Xiangning Xue, Ryan Salisbury, Micah A Shelton, Sam-Moon Kim, Mariah A Hildebrand, Jill R Glausier, Zachary Freyberg, George C Tseng, Anastasia K Yocum and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
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  5. Human Cerebral Blood Flow Activity with Diurnal Variation Differentially Correlated with the Suprachiasmatic Nucleus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
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  9. BioClocks UK: driving robust cycles of discovery to impact.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
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  11. Proteomic insights into the biology of dopaminergic neurons.Frontiers in molecular neuroscience · 2025
    Review
  12. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Stephanie PuigDepartment of Pharmacology, Physiology and Biophysics, Boston University School of Medicine, Boston, MA, USA.
Xiangning XueDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-5775-1193
Ryan SalisburyDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Micah A SheltonDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sam-Moon KimDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mariah A HildebrandDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-4159-4047
Jill R GlausierDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-9838-3414
Zachary FreybergDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-6460-0118
George C TsengDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-5447-1014
Anastasia K YocumA2IDEA, LLC, Ann Arbor, MI, USA.
David A LewisDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-3225-6778
Marianne L SeneyDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-6401-9494
Matthew L MacDonaldDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. macdonaldml@upmc.edu.
Ryan W LoganDepartment of Pharmacology, Physiology and Biophysics, Boston University School of Medicine, Boston, MA, USA. ryan.logan@umassmed.edu.ORCID 0000-0001-8579-015X
University of Pittsburgh · USBoston University · US

Funding

Cell-type specific role of circadian-dependent transcription in fentanyl-induced synaptic and behavioral plasticity - SupplementR01HL150432 · NHLBI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LOGAN, RYAN W · 2019 to 2020
$2.0M
Molecular rhythm alterations in human post-mortem brain associated with opioid use disorderR01DA051390 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOGAN, RYAN W, SENEY, MARIANNE L · 2020 to 2023
$1.9M
NHLBI NIH HHS R01 HL150432NIDA NIH HHS R01 DA051390
6 · The paper itself

Abstract

Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions. Understanding the neurobiological underpinnings of circadian rhythms and opioid use disorder (OUD) may prove valuable for developing new treatments for opioid addiction. Previous work indicated molecular rhythm disruptions in the human brain associated with OUD, highlighting synaptic alterations in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc)-key brain regions involved in cognition and reward, and heavily implicated in the pathophysiology of OUD. To provide further insights into the synaptic alterations in OUD, we used mass-spectrometry based proteomics to deeply profile protein expression alterations in bulk tissue and synaptosome preparations from DLPFC and NAc of unaffected and OUD subjects. We identified 55 differentially expressed (DE) proteins in DLPFC homogenates, and 44 DE proteins in NAc homogenates, between unaffected and OUD subjects. In synaptosomes, we identified 161 and 56 DE proteins in DLPFC and NAc, respectively, of OUD subjects. By comparing homogenate and synaptosome protein expression, we identified proteins enriched specifically in synapses that were significantly altered in both DLPFC and NAc of OUD subjects. Across brain regions, synaptic protein alterations in OUD subjects were primarily identified in glutamate, GABA, and circadian rhythm signaling. Using time-of-death (TOD) analyses, where the TOD of each subject is used as a time-point across a 24-h cycle, we were able to map circadian-related changes associated with OUD in synaptic proteomes associated with vesicle-mediated transport and membrane trafficking in the NAc and platelet-derived growth factor receptor beta signaling in DLPFC. Collectively, our findings lend further support for molecular rhythm disruptions in synaptic signaling in the human brain as a key factor in opioid addiction.

Indexed as

Nucleus AccumbensOpioid-Related DisordersCircadian RhythmDorsolateral Prefrontal CortexHumansPrefrontal CortexProteomeProteome

Identifiers

PMID37674018
PMCPMC10914630
OpenAlexW4386477754

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.