Department of Psychology, University of Oslo, Oslo, Norway.
Department of Physics and Computational Radiology, Oslo University Hospital, Oslo, Norway.
Transl Psychiatry. 2024 Sep 17;14(1):379. doi: 10.1038/s41398-024-03088-3.
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 We included data from 8 publications and 2 unpublished projects, totalling 17 outcomes (N = 455) sourced from a final literature search in Web of Science, Scopus, PubMed and EMBASE on October 12, 2023, and through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 = 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.
社交联系对于所有社交物种的健康和生存至关重要，而这种联系依赖于非人类哺乳动物中的μ-阿片样物质信号。越来越多的神经影像学和精神药理学文献也表明μ-阿片类物质在人类社交联系中发挥作用。为了确定μ-阿片类物质在健康人群中的社交联系中的作用，我们对随机双盲安慰剂对照阿片拮抗剂研究进行了预先注册的（https://osf.io/x5wmq）多水平随机效应荟萃分析。我们纳入了 8 项已发表的和 2 项未发表的研究的数据，这些数据来自于 2023 年 10 月 12 日在 Web of Science、Scopus、PubMed 和 EMBASE 上进行的最终文献检索，以及社区贡献。所有研究均使用纳曲酮（25-100mg）阻断μ-阿片系统，并通过自我报告测量社交联系。阿片拮抗剂略微降低了社交联系的感觉（Hedges'g [95%CI] =-0.20 [-0.32，-0.07]）。研究结果在内部和之间高度一致（I=23%）。然而，在较小的研究中，存在一些偏向于更大效应的迹象（Egger 检验：B=-2.16，SE=0.93，z=-2.33，p=0.02），并且出版偏倚分析表明，纳曲酮的效应可能被高估了。研究结果清楚地表明，完整的μ-阿片样物质信号对于体验社交联系并不是必不可少的，因为即使在完全药理学的μ-阿片样物质阻断下，仍然存在强烈的联系感。然而，拮抗作用降低了社交联系的测量，这与μ-阿片类物质对人类社交联系的调节作用一致。与非人类动物中的发现相比，相对较小的效应大小可能与测量方式的差异（人类的主观反应与动物的行为/动机指标）、物种特异性的神经机制或纳曲酮对其他阿片受体亚型的作用有关。总之，这些结果有助于解释μ-阿片类物质失调和社交脱节如何导致残疾，以及相反地，社交联系如何缓冲健康不良的风险。
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