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Addictions Neuroclinical Assessment: A Neuroscience-Based Framework for Addictive Disorders
Open accessAbstract
This paper proposes a heuristic framework for an Addictions Neuroclinical Assessment (ANA) that incorporates key functional domains derived from the neurocircuitry of addiction. We review how addictive disorders (AD) are presently diagnosed, and the need for new neuroclinical measures to differentiate patients who meet clinical criteria for addiction to the same agent while differing in etiology, prognosis and treatment response. The need for a better understanding of the mechanisms provoking and maintaining addiction, as evidenced by the limitations of current treatments and within-diagnosis clinical heterogeneity, is articulated. In addition, recent changes in the nosology of AD, challenges to current classification systems, and prior attempts to subtype individuals with AD are described. Complementary initiatives, including the Research Domain Criteria (RDoC) project, which have established frameworks for the neuroscience of psychiatric disorders, are discussed. Three domains, executive function, incentive salience, and negative emotionality, tied to different phases in the cycle of addiction, form the core functional elements of AD. Measurement of these domains in epidemiologic, genetic, clinical, and treatment studies will provide the underpinnings for an understanding of cross-population and temporal variation in addictions, shared mechanisms in addictive disorders, impact of changing environmental influences, and gene identification. Finally, we show that it is practical to implement such a deep neuroclinical assessment using a combination of neuroimaging and performance measures. Neuroclinical assessment is key to reconceptualizing the nosology of AD on the basis of process and etiology, an advance that can lead to improved prevention and treatment.
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“Advances in diagnosis that reflect such an endophenotype or research domain criterion approach will synergistically combine with advances in neurobiology to promote novel pharmacotherapeutic, brain stimulation (ie, transcranial magnetic stimulation and direct electrical stimulation), and behavioural treatments.186”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [186]
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“Using the Addictions Neuroclinical Assessment, five subdomains of negative emotional states that can be operationally measured in human laboratory settings and paralleled by animal models were outlined (Kwako et al., 2016).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Kwako et al., 2016
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In the citing paper
“From a nosology perspective, the Addictions Neuroclinical Assessment framework allows the identification of individuals with phenotypes that signal dysregulation in this domain (Kwako et al., 2016).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Kwako et al., 2016
Experimental — accuracy not yet measuredIn the citing paper
“a neurofunctional domain that is postulated to be relevant to early onset of risky alcohol use and the development and maintenance of AUDs (15).”
From Impact of Childhood Trauma on Executive Function in Adolescence—Mediating Functional Brain Networks and Prediction of High-Risk Drinking (2020) · cites this paper as [15]
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“third, it integrates measures for an understanding of the overall functioning of a domain”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [2]
In the citing paper
“The ANA domains, which encompass only a small fraction of the biomarker space for addiction, are incentive salience (see Glossary), negative emotionality, and executive function [2].”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [2]
In the citing paper
“The ANA domains, which encompass only a small fraction of the biomarker space for addiction, are incentive salience (see Glossary), negative emotionality, and executive function [2].”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [2]
In the citing paper
“fourth, it is a research approach for assessment of addiction, not capable, or intended to diagnose DSM-based alcohol/substance use disorders.”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [2]
In the citing paper
“first, it targets measures towards domains that are mechanistically important”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [2]
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Cannabidiol and Alcohol Use Disorders: An Updated Review of Therapeutic Potential
Pince, C. L., Hetelekides, E. M., Schacht, J. P., Gowin, J. L., Bidwell, L. C., & Karoly, H. C. (2026) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70377
Zaur, A. J., Sidhu, N. K., Jin, J. J., Cassidy, S., & Lechner, W. V. (2026) · Addictive Behaviors · doi:10.1016/j.addbeh.2026.108861
Efficacy and Tolerability of Zonisamide for Alcohol Use Disorder
Obitulata, V., Sehgal, K., Florez, J. D. F., Mussi, M., Nero, N., Newton, K., Iqbal, M., Alessi, M. R., & Anand, A. (2026) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000002259
Scarth, M., Bjørnebekk, A., & Walderhaug, E. (2026) · Journal of Substance Use and Addiction Treatment · doi:10.1016/j.josat.2026.210134
Palombo, P., Hovland, S. E., Schmidt, A., Akana, N., Ryan, R., Stark, B. C., Rodin, N. M., White, S., Kogan, C. J., Noto, A. R., et al. (2026) · JMIR Research Protocols · doi:10.2196/102363
Castiglione, G., & Piazza, R. (2026) · EDUCATIONAL REFLECTIVE PRACTICES · doi:10.3280/erpoa1-2025oa20446
Metadata
- Authors
- Kwako, L. E., Momenan, R., Litten, R. Z., Koob, G. F., & Goldman, D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kwako, Laura E.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 80
- Issue
- 3
- Pages
- 179-189
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4870153
- OpenAlex
- W2207035985
- Semantic Scholar
- 621a35dbbd45d7e898e2999389a1fe6c88ac4688
- Cited by
- 395
- References
- 151
- Citations by year
- 2026: 48 · 2025: 32 · 2024: 46 · 2023: 38 · 2022: 43 · 2021: 47 · 2020: 38 · 2019: 46 · 2018: 24 · 2017: 27 · 2016: 6
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99‐AA999999)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- addiction, executive function, incentive salience, negative affectivity, addiction classification, Research Domain Criteria, neuroimaging, clinical heterogeneity, causes of addiction
- MeSH terms
- Emotions, Humans, Models, Psychological, Motivation, Neuropsychological Tests, Behavior, Addictive, Substance-Related Disorders, Executive Function, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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