{"title":"内源性μ-阿片对人类社会联系的调节:系统回顾和荟萃分析","authors":"Guro Løseth, Martin Trøstheim, Siri Leknes","doi":"10.1038/s41398-024-03088-3","DOIUrl":null,"url":null,"abstract":"<p>Social bonding, essential for health and survival in all social species, depends on mu-opioid signalling in non-human mammals. A growing neuroimaging and psychopharmacology literature also implicates mu-opioids in human social connectedness. To determine the role of mu-opioids for social connectedness in healthy humans, we conducted a preregistered (https://osf.io/x5wmq) multilevel random-effects meta-analysis of randomised double-blind placebo-controlled opioid antagonist studies. We included data from 8 publications and 2 unpublished projects, totalling 17 outcomes (N = 455) sourced from a final literature search in Web of Science, Scopus, PubMed and EMBASE on October 12, 2023, and through community contributions. All studies used naltrexone (25–100 mg) to block the mu-opioid system and measured social connectedness by self-report. Opioid antagonism slightly reduced feelings of social connectedness (Hedges’ g [95% CI) = −0.20] [−0.32, −0.07]. Results were highly consistent within and between studies (<i>I</i><sup>2</sup> = 23%). However, there was some indication of bias in favour of larger effects among smaller studies (Egger’s test: <i>B</i> = −2.16, <i>SE</i> = 0.93, <i>z</i> = −2.33, <i>p</i> = 0.02), and publication bias analysis indicated that the effect of naltrexone might be overestimated. The results clearly demonstrate that intact mu-opioid signalling is not essential for experiencing social connectedness, as robust feelings of connectedness are evident even during full pharmacological mu-opioid blockade. Nevertheless, antagonism reduced measures of social connection, consistent with a modulatory role of mu-opioids for human social connectedness. The modest effect size relative to findings in non-human animals, could be related to differences in measurement (subjective human responses versus behavioural/motivation indices in animals), species specific neural mechanisms, or naltrexone effects on other opioid receptor subtypes. In sum, these results help explain how mu-opioid dysregulation and social disconnection can contribute to disability, and conversely—how social connection can buffer risk of ill health.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Endogenous mu-opioid modulation of social connection in humans: a systematic review and meta-analysis\",\"authors\":\"Guro Løseth, Martin Trøstheim, Siri Leknes\",\"doi\":\"10.1038/s41398-024-03088-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Social bonding, essential for health and survival in all social species, depends on mu-opioid signalling in non-human mammals. A growing neuroimaging and psychopharmacology literature also implicates mu-opioids in human social connectedness. To determine the role of mu-opioids for social connectedness in healthy humans, we conducted a preregistered (https://osf.io/x5wmq) multilevel random-effects meta-analysis of randomised double-blind placebo-controlled opioid antagonist studies. We included data from 8 publications and 2 unpublished projects, totalling 17 outcomes (N = 455) sourced from a final literature search in Web of Science, Scopus, PubMed and EMBASE on October 12, 2023, and through community contributions. All studies used naltrexone (25–100 mg) to block the mu-opioid system and measured social connectedness by self-report. Opioid antagonism slightly reduced feelings of social connectedness (Hedges’ g [95% CI) = −0.20] [−0.32, −0.07]. Results were highly consistent within and between studies (<i>I</i><sup>2</sup> = 23%). However, there was some indication of bias in favour of larger effects among smaller studies (Egger’s test: <i>B</i> = −2.16, <i>SE</i> = 0.93, <i>z</i> = −2.33, <i>p</i> = 0.02), and publication bias analysis indicated that the effect of naltrexone might be overestimated. The results clearly demonstrate that intact mu-opioid signalling is not essential for experiencing social connectedness, as robust feelings of connectedness are evident even during full pharmacological mu-opioid blockade. Nevertheless, antagonism reduced measures of social connection, consistent with a modulatory role of mu-opioids for human social connectedness. The modest effect size relative to findings in non-human animals, could be related to differences in measurement (subjective human responses versus behavioural/motivation indices in animals), species specific neural mechanisms, or naltrexone effects on other opioid receptor subtypes. In sum, these results help explain how mu-opioid dysregulation and social disconnection can contribute to disability, and conversely—how social connection can buffer risk of ill health.</p>\",\"PeriodicalId\":23278,\"journal\":{\"name\":\"Translational Psychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41398-024-03088-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-024-03088-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Endogenous mu-opioid modulation of social connection in humans: a systematic review and meta-analysis
Social bonding, essential for health and survival in all social species, depends on mu-opioid signalling in non-human mammals. A growing neuroimaging and psychopharmacology literature also implicates mu-opioids in human social connectedness. To determine the role of mu-opioids for social connectedness in healthy humans, we conducted a preregistered (https://osf.io/x5wmq) multilevel random-effects meta-analysis of randomised double-blind placebo-controlled opioid antagonist studies. We included data from 8 publications and 2 unpublished projects, totalling 17 outcomes (N = 455) sourced from a final literature search in Web of Science, Scopus, PubMed and EMBASE on October 12, 2023, and through community contributions. All studies used naltrexone (25–100 mg) to block the mu-opioid system and measured social connectedness by self-report. Opioid antagonism slightly reduced feelings of social connectedness (Hedges’ g [95% CI) = −0.20] [−0.32, −0.07]. Results were highly consistent within and between studies (I2 = 23%). However, there was some indication of bias in favour of larger effects among smaller studies (Egger’s test: B = −2.16, SE = 0.93, z = −2.33, p = 0.02), and publication bias analysis indicated that the effect of naltrexone might be overestimated. The results clearly demonstrate that intact mu-opioid signalling is not essential for experiencing social connectedness, as robust feelings of connectedness are evident even during full pharmacological mu-opioid blockade. Nevertheless, antagonism reduced measures of social connection, consistent with a modulatory role of mu-opioids for human social connectedness. The modest effect size relative to findings in non-human animals, could be related to differences in measurement (subjective human responses versus behavioural/motivation indices in animals), species specific neural mechanisms, or naltrexone effects on other opioid receptor subtypes. In sum, these results help explain how mu-opioid dysregulation and social disconnection can contribute to disability, and conversely—how social connection can buffer risk of ill health.
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.