Both clinical autism and autistic traits are associated with reduced connectivity between brain regions involved in sensory processing, according to new research published in Scientific Reports. The study, which controlled for familial factors by examining pairs of twins, provides new insights into the neural underpinnings of both clinical autism and autistic traits.
Autism refers to a neurodevelopmental condition characterized by challenges in social and communication functioning, repetitive behaviors, restricted interests, and alterations in sensory processing. It is considered a spectrum disorder, meaning that it varies in severity and presentation among individuals. Autism is associated with a range of difficulties, including low employment rates, an increased risk of anxiety and depressive disorders, and even premature mortality.
Autism and autistic traits are related concepts, but they refer to different aspects of behavior and characteristics in individuals. Autism (formally known as Autism Spectrum Disorder or ASD) is a clinical diagnosis based on specific criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
Autistic traits, on the other hand, refer to a set of behaviors, characteristics, or features that are associated with autism but do not necessarily meet the diagnostic criteria for autism. In other words, they are subclinical or milder expressions of some of the features seen in autism.
It is widely assumed that atypical brain development and connectivity underlie the features of clinical autism. However, previous neuroimaging studies on brain connectivity in autism have produced inconsistent and inconclusive results. By conducting twin and sibling studies, the researchers aimed to control for genetic and shared environmental factors, allowing them to more precisely investigate how clinical autism and autistic traits were related to brain structure.
“I am fascinated by autism and the brain; and I find it very interesting how differences in the brain are related to differences in behavior and abilities,” said study author Janina Neufeld, an assistant professor at Karolinska Institutet and principal investigator of the Synesthesia and Autism Twin Study.
“We still don’t understand the brain mechanisms underlying autism very well, but understanding them better is crucial for understanding the condition’s overall etiology. With our study we aimed to investigate structural brain correlates of both autism and autistic traits, while implicitly controlling for a large number of genetic and environmental factors by twin design.”
The study employed advanced neuroimaging techniques, specifically Diffusion Tensor Imaging (DTI) with global fiber tracking, to reconstruct the entire white-matter connectome without making predetermined anatomical assumptions.
“By conducting global fiber tracking and limiting the investigated connections to those that are more prominent rather than selecting specific connections of interest, we further aimed to balance between retaining statistical power and avoiding bias. We thereby aimed to generate more reliable, unbiased findings,” Neufeld explained.
The study involved 174 individuals (87 twin pairs) from the Roots of Autism and ADHD Twin Study in Sweden project. The sample included 48 monozygotic twin pairs and 39 dizygotic twin pairs. The twins underwent comprehensive assessments, including standardized diagnostic instruments for clinical autism such as the Autism Diagnostic Interview—Revised (ADI-R) and the autism diagnostic observation schedule (ADOS or ADOS-2). Other neurodevelopmental disorders and psychiatric diagnoses were determined using various clinical tools, and general intellectual ability was assessed using standardized IQ tests.
The researchers observed specific associations between clinical autism and reduced connectivity in certain brain regions and between autistic traits and connectivity involving the hippocampus. Individuals with clinical autism exhibited reduced white matter connectivity between the brainstem and the left cuneus. Individuals with higher levels of autistic traits tended to have reduced white matter connectivity between the left hippocampus and the left parahippocampal gyrus, as well as the left fusiform gyrus.
“We found that both autism diagnosis and autistic traits were linked to reduced connectivity between regions crucial for sensory processing,” Neufeld told PsyPost. “The connections exceeding the statistical threshold differed, suggesting the autism diagnosis and autistic traits differ regarding which brain connections they are most strongly linked to, but the overall connectivity patterns were quite similar, suggesting a partly shared neuronal basis.”
Some associations between clinical autism and connectivity were modulated by age, primarily involving fronto-occipital connections. These interactions were negative, indicating that the influence of clinical autism on brain connectivity between these regions decreased with increasing age. This suggests potential compensatory mechanisms affecting structural network organization during adolescence and early adulthood.
While the main results did not significantly differ between males and females, one specific association between autistic traits and connectivity differed significantly. This association, related to the connectivity between the brainstem and the right inferior frontal gyrus, showed differences between males and females. In males, the association was negative, while in females, it was positive.
The researchers also explored whether genetic or non-shared environmental factors influenced the observed associations by comparing monozygotic and dizygotic twins. The within-pair associations between clinical autism or autistic traits and brain connectivity were similar in both monozygotic and dizygotic twins, with overlapping confidence intervals. This suggests that both genetic and non-shared environmental factors may contribute to these associations, but larger sample sizes are needed to draw more definitive conclusions.
“What makes this study special is that we are comparing individuals with autism or higher autistic traits to their twins without autism or with lower autistic traits,” Neufeld explained. “We are thereby controlling implicitly for all genetic and environmental factors shared by the twins and in addition age (and biological sex since we only included twins of the same sex). In addition, we assessed these within-pair relationships separately in identical and non-identical twins, which allowed some conclusions as to whether the results were strongly influenced by genetic factors.”
“The most important limitation is that the number of autistic individuals in the study, and especially the number of twin pairs where one twin had an autism diagnosis and the other did not was very limited,” Neufeld noted. “Further, many individuals who are diagnosed with autism also have other diagnoses, which can make it hard to separate out effects specific to autism, especially in smaller samples. We addressed this by regressing other conditions. We would have liked to address the effects of age and biological sex or gender in more depth, but we lacked the statistical power for it.”
The study, “Reduced brain connectivity along the autism spectrum controlled for familial confounding by co-twin design“, was authored by Janina Neufeld, Simon Maier, Mirian Revers, Marco Reisert, Ralf Kuja-Halkola, Ludger Tebartz van Elst, and Sven Bölte.
