RT Journal Article
SR Electronic
T1 Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 664086
DO 10.1101/664086
A1 Alex M. Dickens
A1 Faith Borgan
A1 Heikki Laurikainen
A1 Santosh Lamichhane
A1 Tiago Marques
A1 Tuukka Rönkkö
A1 Mattia Veronese
A1 Tuomas Lindeman
A1 METSY Investigators
A1 Tuulia Hyötyläinen
A1 Oliver Howes
A1 Jarmo Hietala
A1 Matej Orešič
YR 2019
UL http://biorxiv.org/content/early/2019/06/20/664086.abstract
AB There is an established, albeit poorly-understood link between psychosis and metabolic abnormalities such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by peripheral activation of the endocannabinoid system (ECS). Our recent data suggest that ECS dysregulation may also play a role in psychosis. With the aim of characterizing the involvement of the central and peripheral ECSs and their mutual associations, here we performed a combined neuroimaging and metabolomic study in patients with first-episode psychosis (FEP) and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n=20 and n=8) and HC (n=20 and n=10), by applying 3D positron emission tomography (PET), using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous endocannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleyl ethanolamide were reduced in FEP individuals, but not in those who were predominantly medication-free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, oleyl ethanolamide and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross-talk and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.