Multimodal associations between brain morphology, immune-inflammatory markers, spatial transcriptomics, and behavioural symptoms in autism spectrum disorder.

Researchers studied 42 males with autism to understand aggressive behaviour, which affects up to 68% of autistic individuals. They found that those showing aggression had higher levels of inflammation markers in their blood and different brain structures compared to non-aggressive participants. Brain scans showed changes in areas controlling emotions and behaviour. The study suggests aggression in autism involves both brain inflammation and structural differences, potentially opening new treatment approaches.

This study examined 42 males with autism aged 11-38 years, comparing those with aggressive behaviour (n=21) to non-aggressive controls (n=21). Researchers investigated behavioural profiles, inflammatory markers in blood, and brain structure differences. Aggressive individuals showed elevated inflammatory markers (TNF-α, IL-6, IL-8, IL-13, IFN-γ, vasopressin, EGF) and distinct brain volume differences, with enlargements in anterior cingulate cortex, orbitofrontal cortex, and hippocampus, but reductions in amygdala, insula, and basal ganglia. Gene expression analysis revealed pro-inflammatory patterns in emotional regulation regions and anti-inflammatory compensation in sensory/cognitive areas.

Aggression was associated with more severe autism symptoms, behavioural disturbances, and poorer quality of life.

Findings suggest aggression in autism may benefit from combined approaches addressing both neuroinflammation and behavioural symptoms. Potential for anti-inflammatory treatments alongside traditional behavioural interventions. Results highlight need for comprehensive assessment of aggression impact on quality of life and core autism symptoms.

Small sample size (42 participants), male-only population, cross-sectional design prevents causal inferences. Brain imaging only available for subset of aggressive participants (n=13). Study type not specified in metadata, limiting interpretation of methodology strength.

Aggressive behaviour is a common and disruptive feature of autism spectrum disorder (ASD), affecting up to 68% of individuals and significantly burdening families and caregivers. Despite its prevalence, the mechanisms underlying aggression in ASD remain poorly understood, with evidence pointing to complex interactions between behavioural, neurobiological, and environmental factors. Emerging research suggests that neuroinflammation, along with structural brain changes, may contribute to aggressive behaviour in ASD. This study investigated the behavioural and neurobiological profiles of individuals with ASD who exhibit aggressive behaviour by examining neuroendocrine and inflammatory markers, structural brain differences, and spatial transcriptomics.

The overarching goal was to identify the mechanisms underlying aggression in ASD and inform potential therapeutic strategies. Forty-two male individuals with ASD aged 11-38 years were included in the study, divided into aggressive (Case; n = 21) and non-aggressive (Control; n = 21) groups based on Modified Overt Aggression Scale scores. A series of standardized questionnaires were used to investigate behaviour patterns and quality of life. Plasma levels of neuroendocrine and inflammatory markers, including cytokines and neuropeptides, were measured using a multiplex assay.

For a subset of aggressive participants (n = 13), MRI scans were acquired, and deformation-based morphometry (DBM) was performed to evaluate structural brain differences. Spatial transcriptomics investigated gene expression patterns in brain regions exhibiting volume alterations. Aggression in ASD was associated with more severe core symptoms (higher CARS scores) and pervasive behavioural disturbances, including hyperactivity, irritability, and stereotypy, as well as poorer quality of life. Aggressive individuals exhibited elevated levels of TNF-α, IL-6, IL-8, IL-13, IFN-γ, vasopressin, and epidermal growth factor (EGF), suggesting a pro-inflammatory state.

Neuroimaging revealed distinct volume differences between patients with high- compared to medium-aggression, with enlargements in the anterior cingulate cortex, orbitofrontal cortex, and hippocampus and reductions in the amygdala, insula, and basal ganglia. Spatial transcriptomics identified two gene expression clusters: regions associated with emotional regulation exhibit overexpression of pro-inflammatory genes. In contrast, sensory and cognitive regions have relative anti-inflammatory gene upregulation, potentially reflective of a compensatory mechanism. This study identifies a complex interplay between heightened neuroinflammation and structural brain differences related to gene expression patterns in aggressive ASD.

The findings suggest that aggression is associated with imbalances in the fronto-limbic-striatal network, compounded by a pervasive pro-inflammatory state. These insights highlight the potential for targeted interventions integrating behavioural therapies with adjunctive treatments addressing neuroinflammation and neural dysregulation. Future research should explore longitudinal dynamics, genetic and environmental influences, and broader ASD populations to develop personalized strategies for managing aggression in ASD.