Recent studies show that individuals diagnosed with autism may present either strong or weak neural connectivity patterns. These variations are linked to distinct mechanisms within the brain, hinting at the existence of multiple autism subtypes.

“We have identified major autism subtypes associated with differing biological mechanisms,” notes Alessandro Gozzi from the Italian Polytechnic University in Rovereto.

Autism, often viewed through the lens of neurodiversity, affects approximately 780 individuals per 100,000. Common traits include social interaction challenges, sensitivity to sensory stimuli, and restricted interests. However, the intensity and manifestation of these traits vary widely.

For years, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used to identify unique autism signatures in the brain. “No definitive single signature has yet been identified,” Gozzi states. Some researchers have observed hyperconnectivity in some brain regions, while others have noted low connectivity or a combination of both patterns.

Many previous studies overlooked autism’s diversity, according to Gozzi. To address this, his team studied 20 mouse models with mutations in genes linked to human autism. fMRI results showed variations in connectivity; eleven strains demonstrated primarily hypoconnectivity while nine showed hyperconnectivity.

“These conflicting connectivity signatures are indicative of different underlying mechanisms,” Gozzi explains. They mapped protein interactions associated with the mutated genes. Mice with lower connectivity showed interactions with synapse-related proteins, while hyperconnected mice interacted with proteins linked to gene regulation and immune function.

Furthermore, the research team analyzed fMRI data from 940 autism patients compared to 1,036 age-matched controls. Among the autistic participants, 24% exhibited hypoconnectivity and 17% hyperconnectivity. “At least two biologically distinct autism subtypes are evident,” Gozzi asserts.

Nevertheless, 59% of the autistic population does not fit into these classifications, potentially due to the specific genes selected for study. “Our findings do not suggest these are the only subtypes,” Gozzi clarifies. These were merely the ones detectable through their research methods.

Natalie Sauerwald, a researcher at New York’s Flatiron Institute, concurs that there may be additional, yet unidentified, subtypes of autism. She emphasizes that this work sheds light on autism’s heterogeneity and the biological factors involved.

Challenges persist in utilizing animal models for autism research. Humans have numerous genes, each with minimal individual effects on autism risk. Consequently, studied mice may not represent the full spectrum of autism, as noted by Sauerwald.

Some of the genes examined also relate to developmental delays. Thus, studies like this may only reflect individuals with autism who experience developmental deviations, rather than those without.

Looking ahead, connecting genetics, brain connectivity, and behavioral traits will be crucial to fully understanding autism’s diversity, according to Sauerwald.