The effects of N-acetyl cysteine on intrinsic functional connectivity and neural alcohol cue reactivity in treatment-seeking individuals with alcohol use disorder: a preliminary study.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2024-08-05 DOI:10.1007/s00213-024-06656-z

Warren B Logge, Paul S Haber, Tristan P Hurzeler, Ellen E Towers, Kirsten C Morley

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Abstract

N-acetyl cysteine (NAC) is a potential pharmacotherapy for alcohol use disorder (AUD), but it is not known whether it modulates neural activation to alcohol cues or intrinsic functional connectivity. We investigated whether NAC attenuates (i) alcohol cue-elicited activation, and (ii) intrinsic functional connectivity compared to placebo in patients with AUD. In this preliminary study, twenty-three individuals (7 females) with moderate-severe AUD received daily NAC (2400 mg/day, n = 9), or a placebo (n = 14) for at least 2 weeks. Participants completed a pre-treatment functional magnetic resonance imaging session (T0) and a post-treatment session (T1) comprising resting-state and visual alcohol cue reactivity task acquisitions. Activation differences between sessions, treatment, and session-by-treatment interaction were assessed. Resting-state functional connectivity examined using 377 node ROI-to-ROIs evaluated whether NAC reduced intrinsic functional connectivity after treatment. There were no differences in alcohol cue reactivity for brain activation or subjective craving between NAC and placebo during treatment or across sessions, or significant interaction. A significant treatment-by-time interaction, with reduced intrinsic connectivity was observed after treatment (T1) for NAC-treated compared to placebo-treated patients in the posterior cingulate node (9, left hemisphere) of the dorsal attentional network and connections to salience, ventral-attentional, somatosensory, and visual-peripheral networks implicated in AUD. NAC reduced intrinsic functional connectivity in patients with moderate-severe AUD after treatment compared to placebo, but did not attenuate alcohol cue-elicited activation. However, the absence of cue reactivity findings may result from low power, rather than the absence of cue reactivity findings associated with NAC. These results provide preliminary evidence that NAC treatment may modulate intrinsic functional connectivity brain activation in patients with alcohol use disorder, but replication in larger studies are required to determine the strength of this effect and any associations with clinical outcomes. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT03879759.

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N-乙酰半胱氨酸对寻求治疗的酒精使用障碍患者内在功能连接性和神经酒精线索反应性的影响：一项初步研究。

N-乙酰半胱氨酸（NAC）是一种治疗酒精使用障碍（AUD）的潜在药物疗法，但它是否能调节神经对酒精线索的激活或内在功能连接尚不清楚。与安慰剂相比，我们研究了 NAC 是否会减轻 AUD 患者的（i）酒精线索诱发的激活和（ii）内在功能连接。在这项初步研究中，23 名中度-重度 AUD 患者（7 名女性）每天接受 NAC（2400 毫克/天，n = 9）或安慰剂（n = 14）治疗至少 2 周。受试者完成了治疗前（T0）和治疗后（T1）的功能磁共振成像检查，包括静息态和视觉酒精线索反应任务采集。评估了不同疗程、不同治疗和不同疗程之间的激活差异。使用 377 个节点 ROI-to-ROIs 检查静息态功能连接，评估 NAC 是否会降低治疗后的内在功能连接。在治疗期间或不同疗程中，NAC 和安慰剂在大脑激活或主观渴求方面的酒精线索反应性没有差异，也没有显著的交互作用。与安慰剂治疗患者相比，NAC治疗患者在治疗后（T1）的背侧注意网络后扣带回节点（9，左半球）以及与注意力突出、腹侧注意、躯体感觉和视觉外周网络的连接中出现了明显的治疗与时间交互作用，这与AUD有关。与安慰剂相比，NAC能减少中度-重度AUD患者治疗后的内在功能连接，但不能减少酒精线索引起的激活。然而，没有线索反应性发现可能是由于功率低造成的，而不是因为没有与 NAC 相关的线索反应性发现。这些结果提供了初步证据，证明NAC治疗可能会调节酒精使用障碍患者大脑固有的功能连接激活，但需要在更大规模的研究中进行复制，以确定这种效应的强度以及与临床结果的任何关联。临床试验注册：临床试验注册：ClinicalTrials.gov Identifier：NCT03879759。

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

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.