The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study.
Adult
Adult Survivors of Child Adverse Events
Adverse Childhood Experiences
Dopamine
/ metabolism
Dopamine D2 Receptor Antagonists
/ pharmacokinetics
Female
Humans
Male
Neostriatum
/ diagnostic imaging
Positron-Emission Tomography
Psychological Trauma
/ diagnostic imaging
Psychotic Disorders
/ diagnostic imaging
Raclopride
/ pharmacokinetics
Receptors, Dopamine D2
/ genetics
Receptors, Dopamine D3
/ metabolism
D2 receptor
PET
childhood trauma
dopamine
psychosis spectrum
striatum
Journal
Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760
Informations de publication
Date de publication:
21 08 2021
21 08 2021
Historique:
pubmed:
21
4
2021
medline:
10
2
2022
entrez:
20
4
2021
Statut:
ppublish
Résumé
Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics. This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined. An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis-stress models. Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.
Sections du résumé
BACKGROUND
Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics.
METHOD
This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined.
RESULTS
An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis-stress models.
CONCLUSIONS
Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.
Identifiants
pubmed: 33876249
pii: 6239032
doi: 10.1093/schbul/sbab034
pmc: PMC8379534
doi:
Substances chimiques
DRD2 protein, human
0
DRD3 protein, human
0
Dopamine D2 Receptor Antagonists
0
Receptors, Dopamine D2
0
Receptors, Dopamine D3
0
Raclopride
430K3SOZ7G
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1495-1508Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.