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[Preprint]. 2024 Oct 28:2024.08.30.24312806.
doi: 10.1101/2024.08.30.24312806.

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

Yuliya S Nikolova  1   2   3 , Anthony C Ruocco  1   2   3   4 , Daniel Felsky  1   2   5 , Shannon Lange  1   2   6   7 , Thomas D Prevot  1   2   8 , Erica Vieira  1   2 , Daphne Voineskos  1   2 , Jeffrey D Wardell  1   2   9 , Daniel M Blumberger  1   2 , Kevan Clifford  1   2 , Ravinder Naik Dharavath  1 , Philip Gerretsen  1   2 , Ahmed N Hassan  1   2 , Sheila K Jennings  10   11 , Bernard Le Foll  1   2 , Osnat Melamed  1   12 , Joshua Orson  10 , Peter Pangarov  1 , Leanne Quigley  13 , Cayley Russell  14 , Kevin Shield  1   2   15 , Matthew E Sloan  1   2   3   7   8 , Ashley Smoke  10   16 , Victor Tang  1   2   7 , Diana Valdes Cabrera  1   17 , Wei Wang  1 , Samantha Wells  1   2   18 , Rajith Wickramatunga  1 , Etienne Sibille  1   2   8 , Lena C Quilty  1   2 ; CDiA Program Study Group
Affiliations

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

Yuliya S Nikolova et al. medRxiv. .

Update in

  • Cognitive Dysfunction in the Addictions (CDiA): protocol for a neuron-to-neighbourhood collaborative research program.
    Nikolova YS, Ruocco AC, Felsky D, Lange S, Prevot TD, Vieira E, Voineskos D, Wardell JD, Blumberger DM, Clifford K, Naik Dharavath R, Gerretsen P, Hassan AN, Hope IM, Irwin SH, Jennings SK, Le Foll B, Melamed O, Orson J, Pangarov P, Quigley L, Russell C, Shield K, Sloan ME, Smoke A, Tang V, Valdes Cabrera D, Wang W, Wells S, Wickramatunga R, Sibille E, Quilty LC. Nikolova YS, et al. Front Psychiatry. 2025 May 19;16:1455968. doi: 10.3389/fpsyt.2025.1455968. eCollection 2025. Front Psychiatry. 2025. PMID: 40462873 Free PMC article.

Abstract

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.

Keywords: addiction; alcohol use disorder; cognition; executive function; preclinical; protocol; substance use disorder; translational.

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