Cognitive Dysfunction in the Addictions (CDiA): A Neuron to Neighbourhood Collaborative Research Program on Executive Dysfunction and Functional Outcomes in Outpatients Seeking Treatment for Addiction
Authors: 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 , Dharavath Ravinder Naik , Gerretsen Philip , Hassan Ahmed N. , Jennings Sheila K. , Le Foll Bernard , Melamed Osnat , Orson Joshua , Pangarov Peter , Quigley Leanne , , Russell Cayley , Shield Kevin , Sloan Matthew E. , Smoke Ashley , Tang Victor , Cabrera Diana Valdes , Wang Wei , Wells Samantha , Wickramatunga Rajith , Sibille Etienne M. , Quilty Lena C. ,   CDiA Program Study Group
Published: August 2024

Background: Substance use disorders (SUDs) are pressing global public health problems. Executive functions (EFs) are prominently featured in mechanistic models of addiction. However, there remain significant gaps in our understanding of EFs in SUDs, including the dimensional relationships of EFs to underlying neural circuits, molecular biomarkers, disorder heterogeneity, and functional ability. To improve health outcomes for people with SUDs, interdisciplinary clinical, preclinical and health services research is needed to inform policies and interventions aligned with biopsychosocial models of addiction. Here, we introduce Cognitive Dysfunction in the Addictions (CDiA), an integrative team-science and translational research program, which aims to fill these knowledge gaps and facilitate research discoveries to enhance treatments for people living with SUDs. Methods: The CDiA Program comprises seven complementary interdisciplinary projects that aim to progress understanding of EF in SUDs and investigate new biological treatment approaches. The projects draw on a diverse sample of adults aged 18-60 (target N=400) seeking treatment for addiction, who are followed prospectively over one year to identify EF domains crucial to recovery. Projects 1-3 investigate SUD symptoms, brain circuits, and blood biomarkers and their associations with both EF domains (inhibition, working memory, and set-shifting) and functional outcomes (disability, quality of life). Projects 4 and 5 evaluate interventions for addiction 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 for those with substance use concerns. Project 7 uses innovative 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. Discussion: The CDiA program has promise to bring scientific domains together to uncover the diverse ways in which EFs are linked to SUD severity and functional recovery. These findings, supported by emerging clinical, preclinical, health service, and whole-person modeling investigations, will facilitate future discoveries about cognitive dysfunction in addiction and could enhance the future clinical care of individuals seeking treatment for SUDs.