Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial
Open accessAbstract
BACKGROUND: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. METHODS: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. RESULTS: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. CONCLUSIONS: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder.
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Nonstimulants have downstream effects that modulate activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate brain connectivity patterns of the central executive network and default mode network.
“Besides, they also have downstream effects that modulate the activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate the brain connectivity patterns of the central executive network and default mode network (Borchert et al., 2019; Farr et al., 2014; Lin & Gau, 2015; Schulz et al., 2012; Shafritz et al., 2004).”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Lin & Gau, 2015
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“…non-stimulants may improve the top-down guidance of attention, thought and working memory in those with ADHD via direct effects on NET in the prefrontal cortex (Borchert et al., 2019; Bymaster et al., 2002; Lin & Gau, 2015; Mechler et al., 2022; Morón, Brockington, Wise, Rocha, & Hope, 2002).”
- Authors
- Lin, H.-Y., & Gau, S. S.-F.
- Affiliations
- National Taiwan University (TW)
- Corresponding author
- Gau, Susan Shur-Fen
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-16
- Volume
- 19
- Issue
- 3
- Pages
- pyv094
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC4815465
- OpenAlex
- W2321159218
- Cited by
- 37
- References
- 12
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 1
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Council
- National Health Research Institutes
- National Taiwan University Hospital
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- atomoxetine, adult ADHD, resting-state functional connectivity, default mode network, dorsal attention network, cognitive control network, affective networks, seed-based functional connectivity, treatment response
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Double-Blind Method, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Psychotropic Drugs, Rest, Case-Control Studies, Treatment Outcome, Adrenergic Uptake Inhibitors, Young Adult
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