The Interplay Between Postsynaptic Striatal D-2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A[C-11]-Raclopride PET Study

Smigielski, Lukasz; Wotruba, Diana; Treyer, Valerie; Roessler, Julian; Papiol, Sergi; Falkai, Peter; Gruenblatt, Edna; Walitza, Susanne und Roessler, Wulf (2021): The Interplay Between Postsynaptic Striatal D-2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A[C-11]-Raclopride PET Study. In: Schizophrenia Bulletin, Bd. 47, Nr. 5: S. 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 D-2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [C-11]-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. D-2/3 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 D-2/3 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0586-7614
• Sprache: Englisch