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Cited by 43Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

Adult attention-deficit/hyperactivity disorder is associated with reduced norepinephrine transporter availability in right attention networks: a (S,S)-O-[11C]methylreboxetine positron emission tomography study

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Ulke, Christine, Rullmann, Michael, Huang, Jue, Luthardt, Julia, Becker, Georg-Alexander, Patt, Marianne, Meyer, Philipp M., Tiepolt, Solveig +3 more·2019·Translational Psychiatry
DOI 10.1038/s41398-019-0619-yPMC PMC6858438
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Abstract

The norepinephrine transporter (NET) has been suggested to play a critical role in attention-deficit/hyperactivity disorder (ADHD). In this prospective controlled study we tested the a-priori-hypothesis that central NET availability is altered in adult ADHD patients compared to healthy controls. Study participants underwent single positron emission tomography-magnetic resonance imaging (PET-MRI). MRI sequences included high resolution T1-MPRAGE data for regions of interest (ROI) delineation and voxel-based morphometry (VBM) and T2-weighted fluid-attenuated inversion-recovery for detection and exclusion of pathological abnormalities. NET availability was assessed by NET-selective (S,S)-O-[ 11 C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with two constraints (MRTM2; reference region: occipital cortex). VBM analysis revealed no difference in local distribution of gray matter between the 20 ADHD patients (9 females, age 31.8 ± 7.9 years, 488 ± 8 MBq injected activity) and the 20 age-matched and sex-matched control participants (9 females, age 32.3 ± 7.9 years, 472 ± 72 MBq). In mixed-model repeated-measures analysis with NET availability as dependent and ROI as repeated measure we found a significant main effect group in fronto-parietal-thalamic-cerebellar regions (regions on the right: F 1,25 = 12.30, p = .002; regions on the left: F 1,41 = 6.80, p = .013) indicating a reduced NET availability in ADHD patients. None of the other investigated brain regions yielded significant differences in NET availability between groups after applying a Benjamini-Hochberg correction at a significance level of 0.05. Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.

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Cited by

Sorted by citations

Authors
Ulke, C., Rullmann, M., Huang, J., Luthardt, J., Becker, G.-A., Patt, M., Meyer, P. M., Tiepolt, S., Hesse, S., Sabri, O., & Strauß, M.
Affiliations
University Hospital Leipzig (DE)
Corresponding author
Ulke, Christine
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2019-11-15
Volume
9
Issue
1
Pages
301-301
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/s41398-019-0619-y
PMC
PMC6858438
OpenAlex
W2987857364
Cited by
43
References
18
Citations by year
2026: 5 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 5 · 2020: 4
FWCI
3.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Roland Ernst Foundation, Project 04/17.
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
adult ADHD, norepinephrine transporter, PET/MRI, attentional networks, right hemisphere, gray matter volume
MeSH terms
Adult, Attention Deficit Disorder with Hyperactivity, Biological Availability, Carbon Radioisotopes, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Thalamus, Tissue Distribution, Case-Control Studies, Radiopharmaceuticals, Positron-Emission Tomography, Norepinephrine Plasma Membrane Transport Proteins, Young Adult

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