Autism spectrum disorder (ASD) is a complex developmental disability that can cause significant social, communication and behavioral challenges. Scientists have made immense progress in autism research over the past several decades, working to discover the causes of ASD and develop effective interventions. While the exact causes of autism are still unknown, research continues to advance our understanding of risk factors and the potential roles of both genetics and environment.
Research investigating possible genetic causes of autism has identified several gene variants and mutations that appear to increase risk. Twin studies provide strong evidence for a genetic influence, finding a higher concordance rate of ASD in monozygotic (identical) twins compared to dizygotic (fraternal) twins. Approximately 10-20% of autism risk is attributed to inherited or de novo gene mutations. Some autism-associated gene mutations are rare but have large effects, while others are common variations that each have small effects. Examples of high-risk gene mutations linked to autism include those found in Fragile X syndrome, tuberous sclerosis, PTEN hamartoma tumor syndrome and Rett syndrome. Researchers are actively working to map the human genome and identify additional rare and common genetic variants involved.
While genetics plays an important role, autism is generally not caused by a single gene. Rather, autism develops from a combination of genetic susceptibility in combination with environmental factors. Prenatal environmental influences under investigation include advanced parental age, certain complications during pregnancy, viral infections during pregnancy such as rubella or cytomegalovirus, and maternal obesity or diabetes. Postnatal factors like premature birth, low birth weight, stress, and chemical exposures are also areas of ongoing research. One hypothesis is that certain genetic risks may make an individual more vulnerable to environmental triggers in developing autism. Autism appears to have a multifaceted etiology involving both genetic and non-genetic components interacting in complex ways.
Brain imaging and postmortem studies provide insight into the neural basis of autism. Several brain regions have been found to differ structurally or functionally in individuals with ASD compared to controls, including areas important for social and emotional processing like the amygdala. Other areas of difference involve the cortex, cerebellum, hippocampus and fusiform gyrus. Functional magnetic resonance imaging (fMRI) research shows atypical patterns of connectivity and information processing in neural networks involved in social cognition and language comprehension. Postmortem examination of autistic brains also points to abnormal numbers of neurons and unusual patterns of cortical organization. Together, these studies help unravel the neurobiology underlying autism’s characteristic symptoms.
Scientists are also working to develop improved animal models of autism that mimic its complex behavioral profile and neurobiology. Mice with engineered mutations in autism-linked genes are being used to test functional hypotheses and screen drug candidates. Modeling higher-order social and communicative impairments in rodents poses unique challenges. Non-human primate models are also providing insights into early development of communicative behavior disrupted in autism. Advancing animal models holds promise for enhancing our mechanistic understanding and accelerating therapeutic progress.
In addition to exploring root biological causes, researchers strive to develop more effective educational, behavioral and medical interventions. Early intensive applied behavior analysis programs have demonstrated the ability to substantially improve outcomes for many young children with ASD. Social skills training, cognitive-behavioral therapy, speech therapy and occupational therapy tailored to individual needs are other mainstay treatment approaches. Medical comorbid conditions like seizures, intellectual disability, anxiety and gastrointestinal issues also require comprehensive management.
Careful screening and early diagnosis, ideally by age 2, is critical to deliver optimum interventions during the rapid developmental period before age 5 when the brain is most malleable. Biomarkers to objectively diagnose autism at its earliest manifestations would accelerate access to timely treatment shown to optimize long-term outcomes. Similarly, tools enabling objective assessment of treatment response would support personalized optimization of each child’s intervention plan over time.
Pharmacological research holds promise for developing medications to specifically target core autism symptoms or commonly associated conditions. Risperidone and other atypical antipsychotics are the only FDA-approved medications for irritability symptoms in children, but often cause adverse effects and do not improve overall functioning. Other avenues of drug investigation include agents modulating serotonin, dopamine, glutamate and GABA systems implicated in preclinical studies. Several hundred clinical drug trials for autism have been undertaken to date though successful outcomes have remained elusive. Developing safe and effective pharmacological options, ideally in combination with behavioral therapies, represents an ongoing high priority.
Considerable progress has been made in autism research since the condition was first described over 75 years ago. Understanding of both biological underpinnings and evidence-based treatments has expanded enormously. Incidence rates of ASD continue rising and affected individuals still face lifelong challenges. Continued progress requires largescale collaborative research combining expertise in genetics, neuroscience, pharmacology, education and clinical care. With persistence and cooperation among scientists, professionals and advocacy communities worldwide, we can hopefully unravel autism’s complexity and bring hope of improved well-being to all those living with this neurodevelopmental condition.
Andrew Stroud