Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity
Authors:   Addiction Cue-Reactivity Initiative (ACRI) Network, Sangchooli Arshiya , Zare-Bidoky Mehran , Fathi Jouzdani Ali , Schacht Joseph , Bjork James M. , Claus Eric D. , Prisciandaro James J. , Wilson Stephen J. , Wüstenberg Torsten , Potvin Stéphane , Ahmadi Pooria , Bach Patrick , Baldacchino Alex , Beck Anne , Brady Kathleen T. , Brewer Judson A. , Childress Anna Rose , Courtney Kelly E. , Ebrahimi Mohsen , Filbey Francesca M. , Garavan Hugh , Ghahremani Dara G. , Goldstein Rita Z. , Goudriaan Anneke E. , Grodin Erica N. , Hanlon Colleen A. , Haugg Amelie , Heilig Markus , Heinz Andreas , Holczer Adrienn , Van Holst Ruth J. , Joseph Jane E. , Juliano Anthony C. , Kaufman Marc J. , Kiefer Falk , Khojasteh Zonoozi Arash , Kuplicki Rayus T. , Leyton Marco , London Edythe D. , Mackey Scott , McClernon F. Joseph , Mellick William H. , Morley Kirsten , Noori Hamid R. , Oghabian Mohammad Ali , Oliver Jason A. , Owens Max , Paulus Martin P. , Perini Irene , Rafei Parnian , Ray Lara A. , Sinha Rajita , Smolka Michael N. , Soleimani Ghazaleh , Spanagel Rainer , Steele Vaughn R. , Tapert Susan F. , Vollstädt-Klein Sabine , Wetherill Reagan R. , Witkiewitz Katie , Yuan Kai , Zhang Xiaochu , Verdejo-Garcia Antonio , Potenza Marc N. , Janes Amy C. , Kober Hedy , Zilverstand Anna , Ekhtiari Hamed 
Published: February 2024

ImportanceIn the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers.ObjectiveTo summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts.Evidence ReviewThe PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders.FindingsThere were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes.Conclusions and RelevanceBased on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.