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The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study


Smigielski, Lukasz; Wotruba, Diana; Treyer, Valerie; Rössler, Julian; Papiol, Sergi; Falkai, Peter; Grünblatt, Edna; Walitza, Susanne; Rössler, Wulf (2021). The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study. Schizophrenia Bulletin, 47(5):1495-1508.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:21 August 2021
Deposited On:03 May 2021 08:40
Last Modified:26 May 2024 01:39
Publisher:Oxford University Press
ISSN:0586-7614
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/schbul/sbab034
PubMed ID:33876249
Full text not available from this repository.