Sina Vetter, Sophia Schnabel, Matthias Reichl, Lea Sirignano, Valery Grinevich, Anne Koopmann, Rainer Spanagel, Falk Kiefer, Wolfgang Sommer, Patrick Bach
{"title":"鼻内催产素能减弱男性和女性酒精使用障碍患者杏仁核对负面情感刺激的反应：一项随机对照交叉试验。","authors":"Sina Vetter, Sophia Schnabel, Matthias Reichl, Lea Sirignano, Valery Grinevich, Anne Koopmann, Rainer Spanagel, Falk Kiefer, Wolfgang Sommer, Patrick Bach","doi":"10.1007/s00213-025-06779-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.</p><p><strong>Objectives: </strong>We aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.</p><p><strong>Methods: </strong>We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.</p><p><strong>Results: </strong>OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, p<sub>FWE</sub>=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).</p><p><strong>Conclusions: </strong>OXY's effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.</p><p><strong>Clinicaltrials registry: </strong>DRKS00026218.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1995-2007"},"PeriodicalIF":3.3000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380973/pdf/","citationCount":"0","resultStr":"{\"title\":\"Intranasal oxytocin blunts amygdala response to negative affective stimuli in males and females with alcohol use disorder: a randomized controlled cross-over trial.\",\"authors\":\"Sina Vetter, Sophia Schnabel, Matthias Reichl, Lea Sirignano, Valery Grinevich, Anne Koopmann, Rainer Spanagel, Falk Kiefer, Wolfgang Sommer, Patrick Bach\",\"doi\":\"10.1007/s00213-025-06779-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.</p><p><strong>Objectives: </strong>We aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.</p><p><strong>Methods: </strong>We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.</p><p><strong>Results: </strong>OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, p<sub>FWE</sub>=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).</p><p><strong>Conclusions: </strong>OXY's effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.</p><p><strong>Clinicaltrials registry: </strong>DRKS00026218.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"1995-2007\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380973/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-025-06779-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06779-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Intranasal oxytocin blunts amygdala response to negative affective stimuli in males and females with alcohol use disorder: a randomized controlled cross-over trial.
Rationale: Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.
Objectives: We aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.
Methods: We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.
Results: OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, pFWE=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).
Conclusions: OXY's effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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