A1 Refereed original research article in a scientific journal

Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder




AuthorsNoppari, Tuomo; Tuisku, Jouni; Lukkarinen, Lasse; Tani, Pekka; Lindberg, Nina; Saure, Emma; Lauerma, Hannu; Tiihonen, Jari; Hirvonen, Jussi; Helin, Semi; Rajander, Johan; Salmi, Juha; Nummenmaa, Lauri

PublisherSpringer Nature

Publication year2025

Journal:European Journal of Nuclear Medicine and Molecular Imaging

ISSN1619-7070

eISSN1619-7089

DOIhttps://doi.org/10.1007/s00259-025-07620-5

Web address https://doi.org/10.1007/s00259-025-07620-5

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/504742267


Abstract
Purpose

Opioid and dopamine receptor systems are implicated in the pathoetiology of autism, but in vivo human brain imaging evidence for their role remains elusive.

Methods

Here, we investigated regional type 2 dopamine and mu-opioid receptor (D2R and MOR, respectively) availabilities and regional interactions between the two neuromodulatory systems associated with autism spectrum disorder (ASD). In vivo positron emission tomography (PET) with radioligands [11 C]raclopride (D2R) and [11 C]carfentanil (MOR) was carried out in 16 adult males with high functioning ASD and 24 age and sex matched controls. A whole brain voxel-wise analysis was tested with Student´s t-test and regional group differences in D2R and MOR receptor availabilities as total and separate were tested with linear mixed models also examining the associations between regional receptor availabilities with correlations.

Results

There were no group differences in whole-brain voxel-wise analysis of D2R, but ROI analysis revealed a lower overall mean availability in striatum of the ASD compared to controls. Post hoc regional analysis revealed reduced D2R availability in nucleus accumbens and globus pallidus of the ASD group. The whole-brain voxel-wise analysis of MOR revealed cuneal/precuneal up-regulation in the ASD group, but there was no overall group difference in the ROI analysis for MOR. MOR down-regulation was observed in the hippocampi of the ASD group in a post hoc analysis. Regional correlations between D2R and MOR availabilities were weaker in the ASD group versus control group in the amygdala and nucleus accumbens.

Conclusions

These alterations may translate to disrupted modulation of social motivation and reward in ASD.


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Funding information in the publication
Open Access funding provided by University of Helsinki (including Helsinki University Central Hospital). This study was supported by the Academy of Finland (grant numbers 294897 and 332225 to L.N); Finnish Governmental Research Funding (VTR) for Turku University Hospital (L.N.), Finnish Governmental Research Funding (VTR) for Helsinki and Turku University Hospital (T.N.).


Last updated on 2025-23-10 at 15:15