title: In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users.
abstract: Serotonergic signaling is considered critical for an appropriate adaptation to stress. We have previously observed that in healthy volunteers, prefrontal serotonin transporter (SERT) binding is positively associated with hypothalamic-pituitary-adrenal (HPA)-axis output in terms of the cortisol awakening response (CAR). Here, we tested (1) if such a correlation persists in a human model of chronic serotonin depletion, namely in 3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') users, and (2) if CAR differed between MDMA users (N = 18) and non-using healthy volunteers (N = 32). Participants underwent SERT brain imaging with [11C]DASB-PET, and performed home-sampling of CAR, defined as the area under curve with respect to cortisol increase from awakening level. When adjusting for age and group, CAR was positively coupled to prefrontal SERT binding (p = 0.006) and MDMA users showed significantly higher CAR than the control group (p = 0.0003). In conclusion, our data confirm the recently described positive association between prefrontal SERT binding and CAR, this time in a human model of serotonin deficiency. Also, we find that CAR was higher in MDMA users relative to non-users. We suggest that the inhibitory control on HPA-axis output is less efficient in the off-balance state established by recent MDMA use, most likely through mechanisms other than those that can be compensated by lowering SERT levels.
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Vibe Gedsoe
authors: VG
authors: Frokjaer
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: David
authors: D
authors: Erritzoe
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Klaus Kähler
authors: KK
authors: Holst
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Kathrine Skak
authors: KS
authors: Madsen
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Patrick MacDonald
authors: PM
authors: Fisher
authors: PET and Cyclotron Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Jacob
authors: J
authors: Madsen
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Claus
authors: C
authors: Svarer
authors: Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit,Copenhagen University Hospital,Rigshospitalet,Denmark.
authors: Gitte Moos
authors: GM
authors: Knudsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000814:Aniline Compounds; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D055030:Drug Users; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D010912:Pituitary-Adrenal Function Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides; D014851:Wakefulness; D055815:Young Adult
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D015415:Biomarkers; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D006854:Hydrocortisone