Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex.

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-10-14 DOI:10.1038/s41398-024-03143-z
Martha MacDonald, Pablo A S Fonseca, Kory R Johnson, Erin M Murray, Rachel L Kember, Henry R Kranzler, R Dayne Mayfield, Daniel da Silva
{"title":"Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex.","authors":"Martha MacDonald, Pablo A S Fonseca, Kory R Johnson, Erin M Murray, Rachel L Kember, Henry R Kranzler, R Dayne Mayfield, Daniel da Silva","doi":"10.1038/s41398-024-03143-z","DOIUrl":null,"url":null,"abstract":"<p><p>Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473550/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-024-03143-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0

Abstract

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
酒精和阿片类药物使用障碍的基因表达模式不同,导致背外侧前额叶皮层内的功能网络发生一致的改变。
物质使用失调症(SUD)表现为不顾不良后果的持续吸毒行为,其中酒精使用失调症(AUD)和阿片类药物使用失调症(OUD)是与高死亡率和经济负担相关的流行形式。酒精使用障碍和阿片类药物使用障碍并发的情况很常见,因此有必要深入了解它们之间错综复杂的相互作用。虽然这些疾病之间的因果联系仍然难以捉摸,但人们假设存在共同的遗传因素。利用公共数据集,我们采用了基因组和转录组分析来探索与 AUD 和 OUD 相关的背外侧前额叶皮层内的保守和独特的分子通路。我们的研究结果揭示了这两种疾病在基因水平上的适度转录组重叠,但在共同的生物通路上却有很大的趋同性。值得注意的是,这些通路主要涉及炎症过程、突触可塑性和关键的细胞内信号调节因子。将转录组数据与最新的全基因组关联研究(GWAS)相结合,不仅证实了我们的转录组发现,还证实了这两种疾病之间有限的共同遗传性。总之,我们的研究表明,虽然酒精和阿片类药物会在基因水平上诱发不同的转录改变,但它们在特定的生物通路上趋于一致,这为同时治疗这两种疾病的新型治疗靶点提供了前景广阔的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
期刊最新文献
Postmortem evidence of decreased brain pH in major depressive disorder: a systematic review and meta-analysis. Depression and metabolic connectivity: insights into the locus coeruleus, HF-rTMS, and anxiety. Converging evidence for functional connections between the lithium response and PI3K-Akt signaling. Exploring mitochondrial blood-based and genetic markers in older adults with mild cognitive impairment and remitted major depressive disorder. Understanding novel neuromodulation pathways in tDCS: brain stem recordings in rats during trigeminal nerve direct current stimulation.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1