Tackling hypo and hyper sensory processing heterogeneity in autism: From clinical stratification to genetic pathways.

Researchers studied sensory differences in autism by looking at both over-sensitivity and under-sensitivity to sensory input. They found that autistic people have more varied sensory experiences compared to non-autistic people, with family members falling somewhere in between. Early genetic findings suggest that brain chemical pathways might be linked to sensory differences, particularly under-sensitivity to sensory input.

This study examined sensory processing differences in autism by developing a differential Short Sensory Profile (dSSP) score that captures the balance between hypo- and hyper-sensory sensitivities. Analyzing data from 1,136 participants across two independent samples (PARIS and LEAP), researchers found significant differences in sensory processing patterns between autistic individuals and controls, with first-degree relatives showing intermediate profiles. The study explored genetic links, finding preliminary associations between hyposensitivity and mutations in GABAergic pathways, which regulate brain excitation/inhibition balance. The dSSP showed high variability among autistic individuals, suggesting heterogeneous sensory profiles within the autism spectrum.

The dSSP may serve as a useful clinical tool for characterizing sensory heterogeneity in autism when combined with additional sensory assessments. The high variability in sensory profiles supports the need for individualized sensory assessment and intervention planning rather than one-size-fits-all approaches.

The dSSP score cannot distinguish between individuals with balanced hypo/hyper sensory symptoms and those with no sensory symptoms, as both result in similar ratio scores of 0. This limitation affects the tool's discriminative ability for certain sensory profiles.

As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data.

To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0.

However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum.