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Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis

Hyötyläinen Tuulia; Hietala Jarmo; Laurikainen Heikki; Howes Oliver; Borgan Faith; Orešič Matej; Lindeman Tuomas; Rönkkö Tuukka; Lamichhane Santosh; Dickens Alex M; Marques Tiago; Veronese Mattia

Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis

Hyötyläinen Tuulia
Hietala Jarmo
Laurikainen Heikki
Howes Oliver
Borgan Faith
Orešič Matej
Lindeman Tuomas
Rönkkö Tuukka
Lamichhane Santosh
Dickens Alex M
Marques Tiago
Veronese Mattia
Katso/Avaa
publisher's pdf (710.0Kb)
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NATURE PUBLISHING GROUP
doi:10.1038/s41537-020-00110-7
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042824385
Tiivistelmä

There is an established, 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 activation of specific cannabinoid targets (endocannabinoid system (ECS)). Our recent data suggest that there is a change in the circulating lipidome at the onset of first episode psychosis (FEP). 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 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 three-dimensional positron emission tomography, using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous cannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleoylethanolamide (OEA) 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, OEA, 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.

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