At-a-Glance

There are significant differences in the gene activity of autistic versus neurotypical brains, particularly in brain regions involved in sensory and language processing.

Background: Previous research indicates that complex interactions among hundreds of genes contribute to autism. In the brain, these genes regulate immune responses, neuronal communication, and the activity (also called the “expression”) of other genes. However, exactly how these changes may lead to autism remains unknown, including whether they are confined to one area of the brain or occur throughout. Transcriptomic analysis is a method used to detect changes in the activity of thousands of genes, rather than focusing on specific genes. This method can be used to help identify patterns of gene expression and biological underpinnings of autism by determining where changes in gene activity occur in the brain, even in genes not previously linked to autism.

Methods & Findings: Researchers conducted analyses of gene activity in 725 post-mortem brain samples from 49 autistic people and 54 neurotypical people. These samples examined 11 distinct regions within the cerebral cortex. The cerebral cortex is the part of the brain involved in sensory processing as well as language, memory, emotion, learning, and decision-making. Researchers identified 4,223 genes that were expressed differently in autistic versus neurotypical brains, and these differences were found across the cerebral cortex. The largest number of differences were observed in the brain regions responsible for vision, space perception and hand-eye coordination, and hearing and language processing. Furthermore, while neurotypical brain regions could be distinguished based on differences in gene expression, gene expression in autistic brain regions showed less variation. Of the 11 brain regions compared, this effect was most prominently observed in the regions responsible for vision, language processing and body image, and speech processing and sensation.

Implications: The differences between neurotypical versus autistic brain regions involved in sensory and language processing correspond with the sensory and language processing difficulties commonly experienced by autistic people. The reduced variation between brain regions in autistic individuals also suggests differences in the development and function of these regions, which may contribute to cognitive differences (e.g., problem-solving). These results illustrate the complexity of autism biology and the importance of continued research to better understand how autism genes contribute to variations in brain connectivity and function.

At-a-Glance

Autistic youth exhibit considerable social strengths and struggle more with performing social skills than with learning them.

Background: Social difficulties are common for autistic youth. It has been long assumed that autistic children experience these difficulties due to atypical social learning and that interventions are best focused on helping them acquire social skills. However, recent evidence suggests social difficulties may instead arise from autistic children not consistently performing behaviors that they have already learned or due to having fewer social skill strengths, or both. Existing assessment tools have been unable to examine the distribution of individuals’ challenges and strengths. However, researchers have developed a new method to disentangle and capture the different kinds of social skills challenges (in acquisition of new skills or performance of skills previously acquired) and social strengths of autistic youth. This method can be used to create a Social Skill Deficits and Strengths Profile (SSDSP) for autistic youth that are descriptive of these nuances.

Methods & Findings: The researchers used the SSDSP to examine social functioning in 150 autistic and 61 non-autistic youth ages 7-17 years. Participants’ parents ranked the frequency and importance of 46 social behaviors for their children. The researchers divided the behaviors into one of three categories: acquisition, performance, and strength. Behaviors ranked as “never occurring” (that the child had not been observed doing previously) and “important or critical” were categorized as social acquisition challenges. Behaviors ranked as “seldomly occurring” (they had been observed before, but not often or consistently) and “important or critical” were categorized as social performance challenges. Behaviors ranked as “almost always occurring” (observed consistently) and “important or critical” were categorized as social skill strengths. After categorizing all ranked behaviors, the researchers calculated participants’ percentage of behaviors in each category. Autistic youth exhibited significantly more acquisition and performance challenges and fewer social skill strengths than non-autistic youth but more social strengths than expected. Among autistic youth, social performance challenges were three times more common than social acquisition challenges and twice as common as social skill strengths.

Implications: Results from this study indicate that while autistic youth exhibit more challenges acquiring and performing social skills than do non-autistic youth, social performance challenges and social strengths were both more common than social acquisition challenges. This indicates that performance challenges may be a core feature of social function in autism, which has long been thought to be dominated by social acquisition issues. It also highlights the presence and importance of substantial social strengths in this population. This study supports the need for interventions that help autistic youth perform the social skills they already know and nurture and foster their existing social strengths.

At-a-Glance

Social communication challenges in older autistic siblings are associated with altered brain development in younger siblings who are eventually diagnosed with ASD.

Background: ASD has a genetic component, and younger siblings of individuals with ASD are more likely to develop ASD themselves. This likelihood is increased if the older sibling with ASD shows high levels of social communication challenges. Thus, social communication traits within families may serve as early markers for inherited, autism-associated genetic factors. Neuroimaging studies have shown that autistic children have different patterns of brain development compared to their neurotypical peers. However, the relationships between these brain development patterns and the inherited genetic factors of autism are unclear. This study aimed to investigate the relationship between the level of ASD traits in the older sibling and the brain development of the younger sibling.

Methods & Findings: This study included 384 pairs of siblings (89 pairs where both siblings had ASD) and looked at how the ASD traits in the older sibling were related to brain development in the younger sibling at 6, 12, and 24 months. Researchers analyzed brain scans of participants to identify differences in the size and function of certain regions of the brain. In a subset of sibling pairs, researchers also examined the functional connectivity (how effectively brain regions communicate with one another) of the younger siblings’ visual system. Among sibling pairs in which both children were ultimately diagnosed with ASD, greater social communication challenges among the older siblings were associated with increased total brain volume, total brain surface area, and visual system surface area in the younger siblings at multiple timepoints. Greater social communication challenges among the older siblings were also associated with altered structural and functional connectivity in the visual systems of the younger siblings at 6 months. These associations were not observed in the younger siblings who were not eventually diagnosed with ASD.

Implications: This study suggested that brain features observed in the MRI scans in early development are related to the level of ASD traits in the family. The results point to a convergence of structural and functional differences in areas of the brain involved in visual processing, indicating that genetic factors influence the early development of the visual circuitry in ASD. As the visual processing of social stimuli (e.g., eyes, faces) is critical early in life, this may shape infants’ experiences of the environment around them and contribute to the development of autism.

At-a-Glance

There is a potential link between emotional dysregulation, self-injurious behavior (SIB), and aggressive behavior among autistic youth in psychiatric hospitals, emphasizing the need for mental and behavioral health support programs and interventions that focus on regulating emotions.

Background: Aggression, self-injurious behavior (SIB; e.g., skin picking), and emotional dysregulation (difficulty managing emotions) are more common among autistic people than the general population. However, few studies have examined whether these are related or whether SIB and aggression are more common during times of emotional dysregulation. SIB and aggression are the most common reasons for psychiatric hospitalization among autistic people. Identifying potential links between emotional dysregulation, SIB, and aggression may help improve mental and behavioral health support for people on the autism spectrum.

Methods & Findings: In this study, researchers observed 53 autistic youth admitted to psychiatric hospitals and recorded when individuals displayed emotional dysregulation, SIB, and/or aggressive behavior. This allowed for natural, real-time observation of behavior. Emotional dysregulation was defined as behaviors indicating agitation or clear negative emotion (e.g., crying, yelling, thrashing). SIB and aggressive behaviors were defined as behaviors likely to harm oneself (e.g., hitting self, pulling one’s own hair) or others (e.g., hitting or throwing objects). These behaviors varied greatly between participants. In the study, 51 participants displayed emotional dysregulation, 42 displayed SIB, and 39 displayed aggressive behaviors. Emotional dysregulation was observed during 49% of instances of SIB and 36% of instances of aggressive behavior. Emotional dysregulation was more likely to come after SIB and aggressive behaviors than to occur before episodes of these behaviors.

Implications: Emotional dysregulation may play a role in the onset and continuation of SIB and aggressive behaviors in some autistic people. These individuals may benefit from behavioral and mental health support programs and interventions that focus on regulating emotions. For other autistic individuals, the results of this study suggest that some instances of SIB and aggression may not be associated with outward indications of emotional dysregulation. Instead, they may be caused by other things, such as a desire for a specific outcome. Alternatively, it is possible that the person could be experiencing an internal state of emotional dysregulation but not showing observable signs externally. Further research could investigate methods of measuring emotional dysregulation that do not rely on observable signs of distress, such as elevated heart rate. Additionally, given the correlation in the literature between restricted and repetitive behaviors and SIB and aggression, future research could explore the relationships between these behaviors.

At-a-Glance

Autistic children with early word loss exhibit a slight delay in some language skills, but the delay does not worsen over time and overall language development is comparable to autistic children without early word loss.

Background: Not all autistic children have the same patterns of language development, and some may experience language regression (the loss of previously acquired words). However, little is known about what causes language regression. Some studies have associated language regression with delayed speech, but others indicate that children with language regression eventually achieve typical language development milestones. This study examined autistic children over time to assess predictors and long-term outcomes of autistic children who experienced language regression early in life.

Methods & Findings: Researchers analyzed data from 408 children diagnosed with ASD. They evaluated parent interviews collected over multiple timepoints to examine the frequency, age of onset, and other factors associated with language regression. The researchers also examined how children with and without language regression developed expressive communication skills (using words to convey ideas; for example, asking questions) and receptive communication skills (using words to understand ideas; for example, following directions). The data revealed that 22% of children in the study experienced language regression. Children with language regression walked and learned their first words before children without language regression, but both groups began using phrases of multiple words at similar ages. Children with language regression exhibited a 3-month delay in skills related to expressive, but not receptive, communication. This delay remained consistent over time. Sociodemographic factors such as biological sex, maternal education, and family income did not differ for children with and without language regression.

Implications: This study shows that although autistic children with language regression experienced a slight delay in expressive communication, the delay did not increase over time and therefore likely became less consequential as children aged. The overall pattern of communication development was the same between children who did and children who did not experience language regression. This indicates that language regression does not predict worse long-term developmental outcomes for children with autism.