Evidence map›Paper›PMID 40204703›Full record

ArticleNature communications2025

Cell type-specific multi-omics analysis of cocaine use disorder in the human caudate nucleus.

Lea Zillich, Annasara Artioli, Veronika Pohořalá, Eric Zillich, Laura Stertz, Hanna Belschner, Ammar Jabali, Josef Frank, Fabian Streit, Diana Avetyan and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Lea ZillichDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Lea.Zillich@zi-mannheim.de.ORCID http://orcid.org/0000-0001-7457-374X
Annasara ArtioliDepartment of Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Veronika PohořaláInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Eric ZillichDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-3704-7243
Laura StertzLouis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Hanna BelschnerDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Ammar JabaliDepartment of Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-4867-9465
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-1080-4339
Diana AvetyanDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-0126-7474
Maja P VölkerDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Svenja MüllerDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Anita C HanssonInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-1821-3920
Thomas D MeyerLouis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Marcella RietschelDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-5236-6149
Julia LadewigDepartment of Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-5943-7990
Rainer SpanagelGerman Center for Mental Health (DZPG), partner site Mannheim/Heidelberg/Ulm, Mannheim, Germany.ORCID http://orcid.org/0000-0003-2151-4521
Ana M M OliveiraGerman Center for Mental Health (DZPG), partner site Mannheim/Heidelberg/Ulm, Mannheim, Germany.ORCID http://orcid.org/0000-0002-2729-9036
Consuelo Walss-BassLouis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Rick E BernardiInstitute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Philipp KochDepartment of Translational Brain Research, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0003-3713-8786
Stephanie H WittDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID http://orcid.org/0000-0002-1571-1468

Funding

Gene-environment interactions in COCCaINE Use Disorder: Collaborative Case-Control Initiative in Coccaine AddictionR01DA044859 · NIDA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI GRASSI-OLIVEIRA, RODRIGO, SCHMITZ, JOY MARIE · 2017 to 2021
$2.8M
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) 01ZX01909Deutsche Forschungsgemeinschaft (German Research Foundation) 402170461Deutsche Forschungsgemeinschaft (German Research Foundation) 43081111NIDA NIH HHS R01 DA044859
6 · The paper itself

Abstract

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 30,030 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells. We observed 1485 differentially regulated genes and 10,342 differentially accessible peaks, with alterations in MSNs and astrocytes related to neurotransmitter activity and synapse organization. Gene regulatory network analysis identified transcription factors including ZEB1 as exhibiting distinct CocUD-specific subclusters, activating downstream expression of ion- and calcium-channels in MSNs. Further, PDE10A emerged as a potential drug target, showing conserved effects in a rat model. This study highlights cell type-specific molecular alterations in CocUD and provides targets for further investigation, demonstrating the value of multi-omics approaches in addiction research.

Indexed as

Caudate NucleusCocaine-Related DisordersAdultAnimalsAstrocytesFemaleGene Expression ProfilingGene Regulatory NetworksHumansMaleMiddle AgedMultiomicsNeuronsRatsTranscriptome

Identifiers

PMID40204703
PMCPMC11982542

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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.