Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: A pilot fMRI study
Abstract
Twenty-five youth with attention-deficit/hyperactivity disorder (ADHD) were scanned with functional magnetic resonance imaging (fMRI) while performing a Go/No-go task before and after 6-8 weeks of randomized once-daily treatment with either the α₂A-adrenergic receptor agonist guanfacine or placebo. Clinical improvement was greater for guanfacine than placebo and was differentially associated with reduced activation for guanfacine compared with placebo in the right midcingulate cortex/supplementary motor area and the left posterior cingulate cortex.
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The study adds to the majority of previous studies showing either no or negative effects of guanfacine on cognition in children with ADHD.
“Nevertheless, our study adds to the majority of previous studies showing either no (39–42) or negative effects (43) of guanfacine on cognition in children with ADHD, with only a single very small numbered study in 17 adults with ADHD showing cognitive improvement in interference inhibition (44).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [41]
Guanfacine, while improving ADHD symptoms relative to placebo, may not be an optimal drug to improve specific attention measures.
“Together, this suggests that guanfacine, while improving ADHD symptoms relative to placebo (39–41, 43, 44), may not be an optimal drug to improve specific attention measures.”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [41]
The study's findings extend evidence of no acute or chronic effects of guanfacine on cognitive performance in children and adults with ADHD.
“They also extend evidence of no acute or chronic effects of guanfacine on cognitive performance in children and adults with ADHD (39–42).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [41]
The study's findings are in line with the majority of previous negative findings of guanfacine effects on inhibitory measures.
“While this is in line with the majority of the previous negative findings of guanfacine effects on these measures (39, 41, 42), for lisdexamfetamine, some studies of longer-term use found improvement in inhibitory measures (34, 36) while others did not (38).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [41]
Cites
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Pan, N., Ma, T., Liu, Y., Zhang, S., Hu, S., Shekara, A., Cao, H., Gong, Q., & Chen, Y. (2024) · Psychological Medicine · doi:10.1017/s003329172400285x · Cited by 7 · see citing works
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El Masri, S., Kowalczyk, O. S., Chiu, T. H., Criaud, M., Lukito, S., Mazibuko, N., Salazar de Pablo, G., Perez Rodriguez, V., Makos, O., Lam, S.-L., et al. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1676472
- Authors
- Bédard, A.-C. V., Schulz, K. P., Krone, B., Pedraza, J., Duhoux, S., Halperin, J. M., & Newcorn, J. H.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Queens College, CUNY (US)
- Corresponding author
- Schulz, Kurt P.
- Venue
- Psychiatry Research: Neuroimaging
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 231
- Issue
- 3
- Pages
- 353-356
- ISSN
- 0925-4927 (ISSN-L)
- OpenAlex
- W2113900168
- Cited by
- 20
- References
- 5
- Citations by year
- 2025: 6 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2016: 3 · 2015: 1
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatry Research Neuroimaging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Shire Pharmaceuticals, Inc.
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- guanfacine, attention deficit hyperactivity disorder, youth, placebo response, go/no-go task, midcingulate cortex, supplementary motor area, posterior cingulate cortex, treatment response, neural mechanisms
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Motor Cortex, Pilot Projects, Guanfacine, Treatment Outcome, Adrenergic alpha-2 Receptor Agonists
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