Abstract
Objective: Altered synaptic number, structure and function are thought to be key neurobiological mechanisms underpinning many autistic features, as suggested by genetic, post-mortem and animal model research. Yet, until now, in vivo synaptic density in autistic people has not been quantified. Here, we used the 11C-UCB-J positron emission tomography (PET) tracer to investigate synaptic density differences in autistic adults. We hypothesised (1) altered estimated synaptic density in autistic compared to non-autistic adults in the prefrontal cortex, subregions of the temporal cortex, the amygdala, basal ganglia and cerebellum, and that (2) estimated synaptic density correlates with the extent of autistic traits.
Methods: We included 12 autistic adults (9 male), aged 19–58 years, and 27 non-autistic controls (24 male). No participants had co-occurring physical health or developmental conditions. PET imaging was undertaken using the 11C-UCB-J radiotracer, which binds to the synaptic vesicle protein 2A (SV2A). SV2A is found on pre-synaptic boutons; therefore, distribution volume (VT) of 11C-UCB-J is used as a proxy of synaptic density. We measured the extent of overall autistic traits using the AQ10.
Results: In line with our hypothesis, 11C-UCB-J VT was significantly lower in autistic compared to non-autistic adults in the prefrontal cortex and nucleus accumbens, with large effect sizes. 11C-UCB-J VT negatively correlated with autistic traits, both across diagnostic groups (in prefrontal regions and the nucleus accumbens), and within the autism group itself (in the parahippocampal gyrus and substantia nigra).
Conclusions: We report the first in vivo evidence that autistic adults have a significant reduction in synaptic density, implicating brain regions known to be associated with autistic behaviours and cognitive styles. Future work is required to determine how these differences arise and if they have a positive, negative, or neutral impact on the quality of life of autistic people.
Methods: We included 12 autistic adults (9 male), aged 19–58 years, and 27 non-autistic controls (24 male). No participants had co-occurring physical health or developmental conditions. PET imaging was undertaken using the 11C-UCB-J radiotracer, which binds to the synaptic vesicle protein 2A (SV2A). SV2A is found on pre-synaptic boutons; therefore, distribution volume (VT) of 11C-UCB-J is used as a proxy of synaptic density. We measured the extent of overall autistic traits using the AQ10.
Results: In line with our hypothesis, 11C-UCB-J VT was significantly lower in autistic compared to non-autistic adults in the prefrontal cortex and nucleus accumbens, with large effect sizes. 11C-UCB-J VT negatively correlated with autistic traits, both across diagnostic groups (in prefrontal regions and the nucleus accumbens), and within the autism group itself (in the parahippocampal gyrus and substantia nigra).
Conclusions: We report the first in vivo evidence that autistic adults have a significant reduction in synaptic density, implicating brain regions known to be associated with autistic behaviours and cognitive styles. Future work is required to determine how these differences arise and if they have a positive, negative, or neutral impact on the quality of life of autistic people.
| Original language | English |
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| Title of host publication | Developmental Medicine & Child Neurology |
| Publisher | Mac Keith Press |
| Pages | 23-136 |
| Number of pages | 114 |
| Volume | 67 |
| DOIs | |
| Publication status | Published - Jan 2025 |
Publication series
| Name | Developmental medicine and child neurology |
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