Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition with some special characteristics, such as persistent challenges in social communication and interaction, together with restricted, repetitive patterns of behavior, interests, or activities1. It is termed a “spectrum” disorder because its manifestations in individuals vary widely, in terms of severity and presentation, which reflects a diverse range of strengths and challenges.
ASD affects millions globally and its prevalence is only increasing. A data from the U.S. Centers for Disease Control and Prevention (CDC) indicate that ASD affects approximately 1 in 31 children (3.2%) aged 8 years in 2022. This rise is attributed partly to broader diagnostic criteria, increased awareness among professionals and parents leading to earlier identification2.
It is now understood that ASD arises from a complex interplay between genetic predispositions, neurobiological differences, and environmental influences3. This understanding, along with the increasing recognition of ASD, necessitates an urgent need to direct comprehensive research, effective interventions, and inclusive societal frameworks.
Diagnostic criteria and clinical presentation
Currently, the diagnosis of ASD is behavioral, which relies on observation of an individual’s development and patterns of interaction, supplemented by reports from caregivers4. An ASD diagnosis requires persistent deficits in two core domains: social communication and interaction, and restricted, repetitive patterns of behavior, interests, or activities5.
Deficits in social communication and interaction
- Difficulties with back-and-forth conversation, reduced sharing of interests or emotions, and challenges initiating or responding to social interactions6, 7.
- Poorly integrated verbal and nonverbal communication, atypical eye contact, and deficits in using or understanding gestures8-10.
- Difficulties adjusting behavior to social contexts, challenges in sharing imaginative play, and struggles forming or maintaining friendships11, 12.
Restricted, repetitive patterns of behavior, interests, or activities
- Stereotyped or repetitive behaviors, such as repetitive motor movements (e.g., hand flapping), repetitive use of objects (e.g., lining up toys), or repetitive speech (e.g., echolalia)13, 14.
- Extreme distress at small changes, difficulties with transitions, rigid thinking, or adherence to specific routines15.
- Highly restricted interests that are intense or unusual in focus, for example, an obsessive preoccupation with specific facts or objects16.
- Unusual responses to sensory input, such as indifference to temperature, adverse reactions to specific sounds or textures, or unusual visual fascinations17, 18.
For proper diagnosis of ASD, these symptoms must appear in early development, and cause clinically significant impairment in social, occupational, or other important areas of current functioning. Crucially, they should not be better explained by intellectual disability or global developmental delay.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), released by the American Psychiatric Association (APA) in 2013, is used to diagnose mental disorders like ASD19. To capture the spectrum nature of ASD, the DSM-5 specifies three levels of severity: Level 1 (“requiring support”), Level 2 (“requiring substantial support”), and Level 3 (“requiring very substantial support”).
Neurobiological and genetic landscape
The etiology of ASD is complex, as it stems from a confluence of genetic, neurobiological, and environmental factors.
Genetic factors
ASD is a highly heritable condition, but its genetics are complex and don’t follow a simple inheritance pattern20. Studies on twins show that if one identical twin has ASD, there’s a very high chance (40-90%) that the other twin will as well21. Because identical twins share almost all of their genes, this suggests that genes play a big part.
The high heritability of ASD doesn’t mean a single gene is responsible. Instead, over 1,000 genes are associated with ASD risk, many of which regulate brain development, neuronal function, and synaptic communication22. The condition often runs in families23. This indicates an inherited susceptibility.
However, ASD is usually polygenic, meaning it involves the cumulative effect of many common genetic variations24. Only a small percentage of these cases are linked to rare gene mutations or chromosomal abnormalities25. So, the majority of risk comes from the interplay of numerous genes and environmental factors.
Neurobiological basis
While no single brain abnormality defines ASD, research consistently points to differences in brain structure, function, and connectivity26.
Studies often reveal that atypical functional connectivity in brain regions may be the reason behind difficulties with integrating information across different brain areas. This includes less communication between distant brain regions and more intense communication within localized areas. Some studies also indicate atypical brain growth trajectories in early life: accelerated brain growth in infancy followed by slower growth, particularly in areas like the frontal cortex and amygdala27. This might be the contributing factor behind issues with social cognition and emotional processing.
In addition, genetic alterations in ASD are often found to be more distinct in the superficial layers of the cortex, which are involved in higher-order cognitive functions and interhemispheric communication28. Furthermore, many ASD-associated genes encode proteins critical for synaptic function, suggesting dysregulation in synaptic plasticity and development contributes to altered neural circuits29.
Research also finds potential imbalances in neurotransmitter systems, such as glutamate (excitatory) and GABA (inhibitory)30. This has the potential to cause an excitatory-inhibitory imbalance in neural networks.
Environmental factors
Environmental factors aren’t direct causes of autism, but they can modify the risk for individuals who are already genetically susceptible.
A number of factors during pregnancy and birth have been linked to an increased risk of ASD. These include advanced parental age, maternal health conditions during pregnancy, such as obesity, diabetes, and hypertension, as well as severe infections or inflammation31-35. Ongoing research is also exploring the impact of exposure to certain medications (like valproate and thalidomide) and environmental pollutants like traffic pollution and pesticides36-38.
Additionally, perinatal factors, such as prematurity, low birth weight, and complications during birth like a lack of oxygen (hypoxia), have been associated with an elevated risk39-41.
Finally, it is important to clarify that vaccines have been scientifically debunked as a cause of autism42. Decades of rigorous research have found absolutely no causal link between vaccines and ASD.
Interventions and support
Given the spectrum nature of ASD, interventions are highly individualized and typically involve a multidisciplinary approach43. However, early identification and intervention, ideally in toddlerhood, are crucial for improving outcomes44.
Behavioral therapies
- Applied behavior analysis (ABA): ABA is an evidence-based behavioral intervention for ASD45. It focuses on breaking down skills into smaller steps, teaching them systematically, and using positive reinforcement to encourage desired behaviors while reducing challenging ones. ABA-based approaches encompass various strategies like Discrete Trial Training (DTT), Pivotal Response Treatment (PRT), and Early Start Denver Model (ESDM).
- Speech and language therapy: It addresses communication deficits, including expressive and receptive language skills, as well as the social rules of language46. It may also introduce alternative communication methods if needed, such as the Picture Exchange Communication System (PECS).
- Occupational therapy (OT): It helps individuals develop daily living skills, fine and gross motor skills, and addresses sensory processing differences47. The aim is to improve participation in everyday activities.
- Social skills training: It teaches explicit social rules, nonverbal cues, and strategies for navigating social interactions48.
- Parent-mediated interventions: It empowers parents to implement therapeutic strategies within the home environment49.
Pharmacological treatments
No medication cures ASD or its core symptoms directly. However, medications can manage co-occurring conditions and challenging behaviors, after considering benefits versus side effects, and are part of a broader, individualized plan.
- Irritability and aggression: Antipsychotics like risperidone and aripiprazole are FDA-approved for irritability associated with ASD50.
- Anxiety and depression: Selective serotonin reuptake inhibitors (SSRIs) may be prescribed for co-occurring anxiety or depression51.
- ADHD symptoms: Attention-deficit/hyperactivity disorder (ADHD) is frequently comorbid with ASD52. Stimulants may be used if ADHD symptoms, such as inattention, hyperactivity, and impulsiveness, are significant.
- Seizures: Anticonvulsants such as valproate are used to manage seizures, which occur in a significant subset of individuals with ASD53.
- Sleep disturbances: Melatonin or other sleep aids may address common sleep problems54.
The neurodiversity movement and lifespan considerations
The neurodiversity movement is playing a significant role to reduce stigma around individuals with ASD, and foster accommodating environments. It advocates that neurological differences are natural variations of the human brain, rather than disorders that need to be “cured.” It advocates for autism “acceptance” and “inclusion” rather than solely “awareness,” emphasizing respect for the unique strengths, perspectives, and contributions of autistic individuals.
There is a growing recognition of the needs of autistic adults, who face unique challenges that persist beyond childhood. Many, particularly women, receive a late diagnosis in adulthood after years of struggle55. These individuals often continue to face social and communication challenges that can affect their relationships and integration into the community.
Despite having valuable skills, autistic adults frequently encounter significant employment barriers. This makes supported employment programs and job coaching crucial56.
Mental health is another major concern, as co-occurring anxiety, depression, and OCD are highly prevalent and often worsened by social isolation and unmet needs57. Furthermore, challenges with executive function, such as planning a grocery list or managing a budget, and sensory sensitivities, like being overwhelmed by loud noises, can make it difficult for autistic individuals to live independently58, 59.
In response to these issues, support for autistic adults increasingly focuses on tailored services. These include vocational training, social skills groups, mental health support, and advocacy for accommodations in both the workplace and daily life48, 60-62.
Future directions: precision and integration
The field of ASD research is highly active. A key area of research involves the identification of reliable biomarkers, such as genetic, neurophysiological, metabolic, and eye-tracking patterns63. Such biomarkers can aid in early diagnosis, predict treatment response, and group people with ASD who have similar characteristics, into smaller, more uniform categories.
Another major goal is moving towards a precision medicine approach for ASD, which involves tailoring treatments based on an individual’s unique genetic profile, neurobiological characteristics, and symptom presentation64. Patient-derived induced pluripotent stem cells and brain organoids are proving invaluable as models for studying individual-specific cellular mechanisms and testing therapies65.
To complement these advancements, continued advancements in neuroimaging techniques are a must to further elucidate brain structure, function, and connectivity differences in ASD66.
Lastly, we shall see greater integration of diverse datasets—multi-omics, neuroimaging, and behavioral—using advanced artificial intelligence and machine learning approaches to uncover deeper insights into ASD heterogeneity and underlying mechanisms67.
Conclusion
Autism spectrum disorder remains a multifaceted and evolving area where the understanding of its diagnostic criteria, genetics, and neurobiology has progressed significantly. However, the journey to fully unravel its complexities and provide comprehensive, individualized support continues, offering considerable hope for enhancing the lives of autistic individuals and their families worldwide.