In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users

TY - JOUR

T1 - In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users

AU - Frokjaer, Vibe Gedsoe

AU - Erritzoe, David

AU - Holst, Klaus Kähler

AU - Madsen, Kathrine Skak

AU - Fisher, Patrick MacDonald

AU - Madsen, Jacob

AU - Svarer, Claus

AU - Knudsen, Gitte Moos

PY - 2014/8/20

Y1 - 2014/8/20

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Aniline Compounds

KW - Biological Markers

KW - Case-Control Studies

KW - Drug Users

KW - Female

KW - Functional Neuroimaging

KW - Humans

KW - Hydrocortisone

KW - Male

KW - Middle Aged

KW - N-Methyl-3,4-methylenedioxyamphetamine

KW - Pituitary-Adrenal Function Tests

KW - Positron-Emission Tomography

KW - Prefrontal Cortex

KW - Saliva

KW - Serotonin Plasma Membrane Transport Proteins

KW - Sulfides

KW - Wakefulness

KW - Young Adult

U2 - 10.1017/S1461145714000066

DO - 10.1017/S1461145714000066

M3 - Journal article

C2 - 24524290

SN - 1461-1457

VL - 17

SP - 1119

EP - 1128

JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

IS - 8

ER -