Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder
Abstract Severe and persistent disruptions to sleep and circadian rhythms are common in people with opioid use disorder (OUD). Preclinical evidence suggests altered molecular rhythms in the brain modulate opioid reward and relapse. However, whether molecular rhythms are disrupted in the brains of pe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-03-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01894-1 |
| _version_ | 1819049195720409088 |
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| author | Xiangning Xue Wei Zong Jill R. Glausier Sam-Moon Kim Micah A. Shelton BaDoi N. Phan Chaitanya Srinivasan Andreas R. Pfenning George C. Tseng David A. Lewis Marianne L. Seney Ryan W. Logan |
| author_facet | Xiangning Xue Wei Zong Jill R. Glausier Sam-Moon Kim Micah A. Shelton BaDoi N. Phan Chaitanya Srinivasan Andreas R. Pfenning George C. Tseng David A. Lewis Marianne L. Seney Ryan W. Logan |
| author_sort | Xiangning Xue |
| collection | DOAJ |
| description | Abstract Severe and persistent disruptions to sleep and circadian rhythms are common in people with opioid use disorder (OUD). Preclinical evidence suggests altered molecular rhythms in the brain modulate opioid reward and relapse. However, whether molecular rhythms are disrupted in the brains of people with OUD remained an open question, critical to understanding the role of circadian rhythms in opioid addiction. Using subjects’ times of death as a marker of time of day, we investigated transcriptional rhythms in the brains of subjects with OUD compared to unaffected comparison subjects. We discovered rhythmic transcripts in both the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), key brain areas involved in OUD, that were largely distinct between OUD and unaffected subjects. Fewer rhythmic transcripts were identified in DLPFC of subjects with OUD compared to unaffected subjects, whereas in the NAc, nearly double the number of rhythmic transcripts was identified in subjects with OUD. In NAc of subjects with OUD, rhythmic transcripts peaked either in the evening or near sunrise, and were associated with an opioid, dopamine, and GABAergic neurotransmission. Associations with altered neurotransmission in NAc were further supported by co-expression network analysis which identified OUD-specific modules enriched for transcripts involved in dopamine, GABA, and glutamatergic synaptic functions. Additionally, rhythmic transcripts in DLPFC and NAc of subjects with OUD were enriched for genomic loci associated with sleep-related GWAS traits, including sleep duration and insomnia. Collectively, our findings connect transcriptional rhythm changes in opioidergic, dopaminergic, GABAergic signaling in the human brain to sleep-related traits in opioid addiction. |
| first_indexed | 2024-12-21T11:28:18Z |
| format | Article |
| id | doaj.art-43b3ac45174a411ebb11c7be28c9cd6c |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-21T11:28:18Z |
| publishDate | 2022-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-43b3ac45174a411ebb11c7be28c9cd6c2022-12-21T19:05:36ZengNature Publishing GroupTranslational Psychiatry2158-31882022-03-0112111310.1038/s41398-022-01894-1Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorderXiangning Xue0Wei Zong1Jill R. Glausier2Sam-Moon Kim3Micah A. Shelton4BaDoi N. Phan5Chaitanya Srinivasan6Andreas R. Pfenning7George C. Tseng8David A. Lewis9Marianne L. Seney10Ryan W. Logan11Department of Biostatistics, University of PittsburghDepartment of Biostatistics, University of PittsburghTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of MedicineTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of MedicineTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of MedicineDepartment of Computational Biology, Carnegie Mellon UniversityDepartment of Computational Biology, Carnegie Mellon UniversityDepartment of Computational Biology, Carnegie Mellon UniversityDepartment of Biostatistics, University of PittsburghTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of MedicineTranslational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of MedicineDepartment of Pharmacology and Experimental Therapeutics, Boston University School of MedicineAbstract Severe and persistent disruptions to sleep and circadian rhythms are common in people with opioid use disorder (OUD). Preclinical evidence suggests altered molecular rhythms in the brain modulate opioid reward and relapse. However, whether molecular rhythms are disrupted in the brains of people with OUD remained an open question, critical to understanding the role of circadian rhythms in opioid addiction. Using subjects’ times of death as a marker of time of day, we investigated transcriptional rhythms in the brains of subjects with OUD compared to unaffected comparison subjects. We discovered rhythmic transcripts in both the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), key brain areas involved in OUD, that were largely distinct between OUD and unaffected subjects. Fewer rhythmic transcripts were identified in DLPFC of subjects with OUD compared to unaffected subjects, whereas in the NAc, nearly double the number of rhythmic transcripts was identified in subjects with OUD. In NAc of subjects with OUD, rhythmic transcripts peaked either in the evening or near sunrise, and were associated with an opioid, dopamine, and GABAergic neurotransmission. Associations with altered neurotransmission in NAc were further supported by co-expression network analysis which identified OUD-specific modules enriched for transcripts involved in dopamine, GABA, and glutamatergic synaptic functions. Additionally, rhythmic transcripts in DLPFC and NAc of subjects with OUD were enriched for genomic loci associated with sleep-related GWAS traits, including sleep duration and insomnia. Collectively, our findings connect transcriptional rhythm changes in opioidergic, dopaminergic, GABAergic signaling in the human brain to sleep-related traits in opioid addiction.https://doi.org/10.1038/s41398-022-01894-1 |
| spellingShingle | Xiangning Xue Wei Zong Jill R. Glausier Sam-Moon Kim Micah A. Shelton BaDoi N. Phan Chaitanya Srinivasan Andreas R. Pfenning George C. Tseng David A. Lewis Marianne L. Seney Ryan W. Logan Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder Translational Psychiatry |
| title | Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| title_full | Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| title_fullStr | Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| title_full_unstemmed | Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| title_short | Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| title_sort | molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder |
| url | https://doi.org/10.1038/s41398-022-01894-1 |
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