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Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review | Radiology | JAMA Psychiatry | ÁñÁ«ÊÓƵ Network

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Review
February 7, 2024

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review

Addiction Cue-Reactivity Initiative (ACRI) Network
JAMA Psychiatry. 2024;81(4):414-425. doi:10.1001/jamapsychiatry.2023.5483
Key Points

QuestionÌý What is the current status of functional magnetic resonance imaging drug cue reactivity (FDCR) research, and how could it support the discovery of biomarkers to facilitate intervention development and clinical care for substance use disorders?

FindingsÌý In this systematic review including 415 FDCR studies, results from 357 studies could potentially help develop diagnostic, prognostic, susceptibility, severity, monitoring, predictive, or response biomarkers. Substantial heterogeneity in task and study design was identified that can hinder biomarker development.

MeaningÌý A sizable literature supports the development of FDCR-derived biomarkers, but moving forward requires large-scale collaboration, methodological harmonization and optimization, and clinical and analytical validation.

Abstract

ImportanceÌý In 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.

ObjectiveÌý To 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 ReviewÌý The 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.

FindingsÌý There 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 RelevanceÌý Based 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.

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