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

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

doi:10.1007/s00259-025-07620-5

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

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

Research output: Contribution to journal › Article › Scientific › peer-review

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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.

Original language	English
Pages (from-to)	2069-2082
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	53
Issue number	3
Early online date	18 Oct 2025
DOIs	https://doi.org/10.1007/s00259-025-07620-5
Publication status	Published - Feb 2026
MoE publication type	A1 Journal article-refereed

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https://urn.fi/URN:NBN:fi-fe2026050136860

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Noppari, T., Tuisku, J., Lukkarinen, L., Tani, P., Lindberg, N., Saure, E., Lauerma, H., Tiihonen, J., Hirvonen, J., Helin, S., Rajander, J., Salmi, J., & Nummenmaa, L. (2026). Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder. European Journal of Nuclear Medicine and Molecular Imaging, 53(3), 2069-2082. https://doi.org/10.1007/s00259-025-07620-5

@article{e89543e7db044e0aba43b3517186ef3a,

title = "Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder",

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.",

author = "Tuomo Noppari and Jouni Tuisku and Lasse Lukkarinen and Pekka Tani and Nina Lindberg and Emma Saure and Hannu Lauerma and Jari Tiihonen and Jussi Hirvonen and Semi Helin and Johan Rajander and Juha Salmi and Lauri Nummenmaa",

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doi = "10.1007/s00259-025-07620-5",

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Noppari, T, Tuisku, J, Lukkarinen, L, Tani, P, Lindberg, N, Saure, E, Lauerma, H, Tiihonen, J, Hirvonen, J, Helin, S, Rajander, J, Salmi, J & Nummenmaa, L 2026, 'Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder', European Journal of Nuclear Medicine and Molecular Imaging, vol. 53, no. 3, pp. 2069-2082. https://doi.org/10.1007/s00259-025-07620-5

TY - JOUR

T1 - Aberrant type 2 dopamine and mu-opioid receptor availability in autism spectrum disorder

AU - Noppari, Tuomo

AU - Tuisku, Jouni

AU - Lukkarinen, Lasse

AU - Tani, Pekka

AU - Lindberg, Nina

AU - Saure, Emma

AU - Lauerma, Hannu

AU - Tiihonen, Jari

AU - Hirvonen, Jussi

AU - Helin, Semi

AU - Rajander, Johan

AU - Salmi, Juha

AU - Nummenmaa, Lauri

PY - 2026/2

Y1 - 2026/2

N2 - 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.

AB - 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.

U2 - 10.1007/s00259-025-07620-5

DO - 10.1007/s00259-025-07620-5

M3 - Article

C2 - 41108393

SN - 1619-7070

VL - 53

SP - 2069

EP - 2082

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 3

ER -

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

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