Nikolova Yuliya S, Ruocco Anthony C, Felsky Daniel, Lange Shannon, Prevot Thomas D, Vieira Erica, Voineskos Daphne, Wardell Jeffrey D, Blumberger Daniel M, Clifford Kevan, Naik Dharavath Ravinder, Gerretsen Philip, Hassan Ahmed N, Hope Ingrid M, Irwin Samantha H, Jennings Sheila K, Le Foll Bernard, Melamed Osnat, Orson Josh, Pangarov Peter, Quigley Leanne, Russell Cayley, Shield Kevin, Sloan Matthew E, Smoke Ashley, Tang Victor, Valdes Cabrera Diana, Wang Wei, Wells Samantha, Wickramatunga Rajith, Sibille Etienne, Quilty Lena C
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Front Psychiatry. 2025 May 19;16:1455968. doi: 10.3389/fpsyt.2025.1455968. eCollection 2025.
Substance use disorders (SUDs), including Alcohol Use Disorder, are pressing global public health problems. Executive functions (EFs) are prominently featured in mechanistic models of addiction. However, significant gaps remain in our understanding of EFs in SUDs, including the dimensional relationships of EFs to underlying neural circuits, molecular biomarkers, disorder heterogeneity, and functional ability. Transforming health outcomes for people with SUDs requires an integration of clinical, biomedical, preclinical, and health services research. Through such interdisciplinary research, we can develop policies and interventions that align with biopsychosocial models of addiction, addressing the complex cognitive concerns of people with SUDs in a more holistic and effective way. Here, we introduce the design and procedures underlying Cognitive Dysfunction in the Addictions (CDiA), an integrative research program, which aims to fill these knowledge gaps and facilitate research discoveries to enhance treatments for people living with SUDs. The CDiA Program comprises seven interdisciplinary projects that aim to evaluate the central thesis that EF has a crucial role in functional outcomes in SUDs. The projects draw on a diverse sample of adults aged 18-60 (target =400) seeking treatment for SUD, who are followed over one year to identify specific EF domains most associated with improved functioning. Projects 1-3 investigate SUD symptoms, brain circuits, and blood biomarkers and their associations with key EF domains (inhibition, working memory, and set-shifting) and functional outcomes (disability, quality of life). Projects 4 and 5 evaluate interventions for SUDs and their impacts on EF: a clinical trial of repetitive transcranial magnetic stimulation and a preclinical study of potential new pharmacological treatments in rodents. Project 6 links EF to healthcare utilization and is supplemented with a qualitative investigation of EF-related barriers to treatment engagement. Project 7 uses whole-person modeling to integrate the multi-modal data generated across projects, applying clustering and deep learning methods to identify patient subtypes and drive future cross-disciplinary initiatives. The CDiA Program will bring scientific domains together to uncover novel ways in which EFs are linked to SUD severity and functional recovery, and facilitate future discoveries to improve health outcomes in individuals living with SUDs.
物质使用障碍（SUDs），包括酒精使用障碍，是紧迫的全球公共卫生问题。执行功能（EFs）在成瘾的机制模型中显著突出。然而，我们对物质使用障碍中的执行功能的理解仍存在重大差距，包括执行功能与潜在神经回路、分子生物标志物、疾病异质性和功能能力的维度关系。改善物质使用障碍患者的健康结局需要整合临床、生物医学、临床前和卫生服务研究。通过此类跨学科研究，我们可以制定与成瘾的生物心理社会模型相一致的政策和干预措施，以更全面、有效的方式解决物质使用障碍患者复杂的认知问题。在此，我们介绍成瘾认知功能障碍（CDiA）这一综合研究项目的设计和程序，其旨在填补这些知识空白，并推动研究发现以加强对物质使用障碍患者的治疗。CDiA项目包括七个跨学科项目，旨在评估执行功能在物质使用障碍功能结局中起关键作用这一核心论点。这些项目采用了年龄在18至60岁（目标为400人）寻求物质使用障碍治疗的成年多样化样本，对他们进行为期一年的跟踪，以确定与功能改善最相关的特定执行功能领域。项目1至3研究物质使用障碍症状、脑回路和血液生物标志物及其与关键执行功能领域（抑制、工作记忆和定势转换）和功能结局（残疾、生活质量）的关联。项目4和5评估物质使用障碍的干预措施及其对执行功能的影响：重复经颅磁刺激的临床试验以及啮齿动物潜在新药理学治疗的临床前研究。项目6将执行功能与医疗保健利用联系起来，并辅以对与治疗参与相关的执行功能障碍的定性调查。项目7使用全人模型整合各项目产生的多模态数据，应用聚类和深度学习方法识别患者亚型并推动未来的跨学科举措。CDiA项目将把各科学领域汇聚在一起，以揭示执行功能与物质使用障碍严重程度和功能恢复相关联的新方式，并推动未来的发现以改善物质使用障碍患者的健康结局。
