Evidence map›Paper›PMID 25338091›Full record

ArticleJAMA psychiatry2014

The norepinephrine transporter in attention-deficit/hyperactivity disorder investigated with positron emission tomography.

Thomas Vanicek, Marie Spies, Christina Rami-Mark, Markus Savli, Anna Höflich, Georg S Kranz, Andreas Hahn, Alexandra Kutzelnigg, Tatjana Traub-Weidinger, Markus Mitterhauser and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in JAMA psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 60 citations in OpenAlex.

  1. Trial
  2. Central noradrenaline transporter availability in highly obese, non-depressed individuals.European journal of nuclear medicine and molecular imaging · 2017
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  4. Maternal immune activation in mice recapitulates features of attention-deficit/hyperactivity disorder (ADHD) in susceptible offspring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Thomas Vanicek *Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Marie Spies *Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Christina Rami-MarkDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Markus SavliDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Anna HöflichDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Georg S KranzDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Andreas HahnDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Alexandra KutzelniggDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Tatjana Traub-WeidingerDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Markus MitterhauserDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Wolfgang WadsakDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Marcus HackerDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Nora D VolkowDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Siegfried KasperDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Rupert LanzenbergerDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (Vanicek, Spies, Savli, Höflich, Kranz, Hahn, Kutzelnigg, Kasper, Lanzenberger); Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria (Rami-Mark, Traub-Weidinger, Mitterhauser, Wadsak, Hacker); National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland (Volkow).
Medical University of Vienna · ATNational Institutes of Health · US

Funding

Neurobiology of Substance Abuse and AddictionZIAAA000550 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI VOLKOW, NORA D. · 2009 to 2025
$115.1M
Austrian Science Fund FWF P 22981
6 · The paper itself

Abstract

importanceAttention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently prescribed medication in ADHD. Therefore, the NET is suggested to play a critical role in ADHD.

objectiveTo explore the differences in NET nondisplaceable binding potential (NET BPND) using positron emission tomography and the highly selective radioligand (S,S)-[18F]FMeNER-D2 [(S,S)-2-(α-(2-[18F]fluoro[2H2]methoxyphenoxy)benzyl)morpholine] between adults with ADHD and healthy volunteers serving as controls. DESIGN, SETTING, AND

participantsTwenty-two medication-free patients with ADHD (mean [SD] age, 30.7 [10.4] years; 15 [68%] men) without psychiatric comorbidities and 22 age- and sex-matched healthy controls (30.9 [10.6] years; 15 [68%] men) underwent positron emission tomography once. A linear mixed model was used to compare NET BPND between groups. MAIN OUTCOMES AND MEASURES: The NET BPND in selected regions of interest relevant for ADHD, including the hippocampus, putamen, pallidum, thalamus, midbrain with pons (comprising a region of interest that includes the locus coeruleus), and cerebellum. In addition, the NET BPND was evaluated in thalamic subnuclei (13 atlas-based regions of interest).

resultsWe found no significant differences in NET availability or regional distribution between patients with ADHD and healthy controls in all investigated brain regions (F1,41<0.01; P=.96). Furthermore, we identified no significant association between ADHD symptom severity and regional NET availability. Neither sex nor smoking status influenced NET availability. We determined a significant negative correlation between age and NET availability in the thalamus (R2=0.29; P<.01 corrected) and midbrain with pons, including the locus coeruleus (R2=0.18; P<.01 corrected), which corroborates prior findings of a decrease in NET availability with aging in the human brain. CONCLUSIONS AND RELEVANCE: Our results do not indicate involvement of changes in brain NET availability or distribution in the pathogenesis of ADHD. However, the noradrenergic transmitter system may be affected on a different level, such as in cortical regions, which cannot be reliably quantified with this positron emission tomography ligand. Alternatively, different key proteins of noradrenergic neurotransmission might be affected.

Indexed as

AdultAge FactorsAttention Deficit Disorder with HyperactivityBrainCase-Control StudiesFemaleFluorine RadioisotopesFunctional NeuroimagingHumansMaleMorpholinesNorepinephrine Plasma Membrane Transport ProteinsPositron-Emission TomographySymptom AssessmentYoung Adult2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholineFluorine RadioisotopesMorpholinesNorepinephrine Plasma Membrane Transport Proteins

Identifiers

PMID25338091
PMCPMC4699255
OpenAlexW2061577104

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.