2026 ECNP Congress

PS01-1136

Reduced nucleus accumbens serotonin 1B receptor availability and its association with synaptic density in adults with autism spectrum disorder

Masamichi Yokokura — T. Tamayama, Y. Kameno, T. Iwabuchi, T. Goto, I. Murata, T. Harada, N. Ichinohe, Y. Ouchi, H. Yamasue · Hamamatsu University School of Medicine, Psychiatry, Hamamatsu, Japan

2026 ECNP Congress

Background

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical social communication and restricted, repetitive behaviors. Despite extensive research, the neurobiological mechanisms underlying the core features of ASD remain unclear. Converging evidence suggests that the serotonergic system plays an important role in social behavior and may contribute to ASD pathophysiology. Alterations in synaptic density have also been reported in ASD, although findings are heterogeneous. Because serotonin (5-HT) 1B receptors are implicated in synaptic formation and plasticity, changes in this receptor system may contribute to synaptic abnormalities observed in ASD. However, in vivo investigations of 5-HT1B receptor availability in individuals with ASD, and its relationship with synaptic density, are currently lacking. This study aimed to provide the first in vivo assessment of 5-HT1B receptor availability in adults with ASD and to examine its association with synaptic density.

Methods

Twenty high-functioning adult males with ASD and 21 age-matched typically developing (TD) males participated in this case–control study. All participants were free from psychotropic medications and major psychiatric comorbidities. 5-HT1B receptor availability was measured using positron emission tomography (PET) with [11C]AZ10419369. Synaptic density was assessed on the same day using [11C]UCB-J PET. Structural magnetic resonance imaging scans were acquired for anatomical localization. Region-of-interest analyses focused on the nucleus accumbens and related regions implicated in ASD. Group differences in [11C]AZ10419369 nondisplaceable binding potential (BPND) values were examined using repeated-measures analysis of variance. Pearson correlation analyses were conducted to explore relationships between receptor availability and clinical measures. To investigate associations between 5-HT1B receptor availability and synaptic density, voxel-wise multiple regression analyses were performed within each diagnostic group using BPND values from regions showing significant group differences (ASD vs TD) as covariates to identify correlated voxels in the [11C]UCB-J standard uptake value ratio (SUVR) images.

Results

Individuals with ASD showed significantly lower [11C]AZ10419369 BPND values in the nucleus accumbens compared with TD participants (Pcorrected < 0.05), but not in other examined regions. No significant correlations were observed between regional 5-HT1B BPND values and clinical symptom measures in either group. Whole-brain voxel-wise regression analysis within the ASD group revealed a significant positive correlation between the nucleus accumbens [11C]AZ10419369 BPND value and [11C]UCB-J SUVR in the cingulate cortex (voxel level: Puncorrected < 0.001, cluster level: Pcorrected < 0.05). This association was not observed in TD participants.

Conclusions

This study provides in vivo evidence of reduced 5-HT1B receptor availability in the nucleus accumbens in adults with ASD. Furthermore, the association between nucleus accumbens 5-HT1B receptor availability and synaptic density in the cingulate cortex suggests that serotonergic dysfunction may be linked to synaptic alterations in ASD. These findings indicate that variability in synaptic pathology in ASD may be partly explained by differences in the 5-HT1B receptor system. Future studies with larger samples and longitudinal designs are warranted to clarify causal relationships and clinical relevance.

References

No references