Autor:innen:
Christine Ulke, Leipzig (Germany)
Michael Rullmann, Leipzig (Germany)
Jue Huang, Leipzig (Germany)
Julia Luthardt, Leipzig (Germany)
Georg-Alexander Becker, Leipzig (Germany)
Marianne Patt, Leipzig (Germany)
Philipp Meyer, Leipzig (Germany)
Solveig Tiepolt, Leipzig (Germany)
Swen Hesse, Leipzig (Germany)
Osama Sabri, Leipzig (Germany)
Alexandra Philipsen, Leipzig (Germany)
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 and explored whether it is associated with ADHD symptom severity (assessed by DSM-IV subscales of the Conners’ adult ADHD rating scales), neuropsychological (omission and commission errors of a sustained attention test) and neurophysiological (EEG extracted frontal theta current source density) measures. Study participants underwent single positron emission tomography magnetic-resonance-imaging (PET-MRI). NET availability was assessed by NET-selective (S,S)-O-[11C]methylreboxetine; regional distribution volume ratios (DVR) were calculated based on individual PET-MRI data co-registration and a multi-linear reference tissue model with 2 constraints (MRTM2; reference region: occipital cortex). We utilized mixed effects repeated-measures models to compare NET availability between groups. Twenty ADHD patients (9 females, age 31.8±7.9 years, 488±8 MBq injected activity) 20 age- and sex-matched healthy controls (9 females, age 32.3±7.9 years, 472±72 MBq) significantly differed in DVR in fronto-parietal-thalamic-cerebellar regions (main effect group: regions on the right side: F1,25=12.30, p=.002; regions on the left side: F1,41=6.80, p=.013). Mean DVR in regions on the right side correlated negatively with ADHD symptom severity (inattention: p=.003; hyperactivity/ impulsivity: p=.011), omission errors in a sustained attention test (p=.003), and with right-frontal theta current density (p=.009). Analogous analyses for the left side did not yield any significant findings (.027≤p≤.885). Overall our findings demonstrate the pathophysiological involvement of NET availability in adult ADHD.