autism spectrum research paper

• Open access
• Published: 10 June 2024

New advances in the diagnosis and treatment of autism spectrum disorders

• Lei Qin 1 ,
• Haijiao Wang 2 ,
• Wenjing Ning 1 ,
• Mengmeng Cui 1 &
• Qian Wang 3  

European Journal of Medical Research volume  29 , Article number:  322 ( 2024 ) Cite this article

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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals' social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic–environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.

Autism spectrum disorders (ASD) are a broad group of neurodevelopmental disorders that affect an individual's social interactions, communication skills, and behavioral patterns [ 1 , 2 ]. The characteristics of ASD vary significantly between individuals, from mild social impairments to severe communication and behavioral problems, a diversity that reflects the use of the term “spectrum” [ 3 ]. Although the exact causes of ASD are not fully understood, research suggests that both genetic and environmental factors play a key role in its development [ 4 ].

Characteristics of ASD

Difficulties in social interaction.

Individuals with ASD often exhibit significant difficulties in social interactions. These difficulties may include difficulty understanding the feelings and intentions of others, maintaining eye contact and facial expressions, and adapting to social norms and expectations. Individuals with ASD may experience challenges in establishing and maintaining friendships, they may not understand the two-way nature of social interactions, or they may feel uncomfortable sharing interests and activities [ 5 ].

Communication disorders

Communication deficits are another core feature of ASD. This may manifest itself in delays in language development, including delays in uttering first words or simple sentences. Some individuals with ASD may not use language to communicate at all. Even among individuals with ASD who have normal language skills, they may have difficulty using language in conversations to communicate thoughts, feelings, or needs. In addition, nonverbal communication, such as the understanding and use of body language and facial expressions, may also be affected [ 6 ].

Repetitive behaviors and interests

Individuals with ASD often display restricted, repetitive patterns of behavior and interests. These may include a strong fixation on specific topics or activities, repetitive body movements (e.g., rocking, clapping), and an overreliance on daily routines. These repetitive behaviors are sometimes seen as a way of self-soothing or as an attempt to control an environment that otherwise feels unpredictable and overwhelming to them [ 7 ].

Sensory sensitivity

Many individuals with ASD have abnormalities in sensory processing and may have very strong or delayed responses to sound, light, touch, taste or odor. For example, some individuals with ASD may find background noises in their everyday environment unusually harsh, or they may not notice pain or other bodily sensations [ 8 ].

Epidemiologic profile of ASD

According to the World Health Organization (WHO), the average prevalence of ASD among children globally is approximately 1% [ 9 ]. However, this figure varies significantly between regions and countries. For example, the Centers for Disease Control and Prevention (CDC) reports that the prevalence of ASD among 8-year-olds in the U.S. is 1 to 54. ASD is significantly more prevalent in males than females, at a ratio of approximately 4:1 [ 10 ]. This gender difference may reflect differences in genetic susceptibility and/or gender bias in the diagnostic process. Early diagnosis is key to improving developmental outcomes for children with ASD. Despite this, many children are not diagnosed by age 3. The CDC reports that most children are first evaluated for ASD by age 4, but diagnosis may occur later. Research suggests that ASD is highly heritable, but multiple genetic variants are associated with disease risk and environmental factors also play a role [ 11 ]. For example, there is an increased risk of ASD in preterm and low birth weight infants. Socioeconomic factors influence ASD diagnosis and treatment access. Families of lower socioeconomic status may face greater challenges, including barriers to accessing early intervention services, etc. ASD is a global public health problem, and its incidence, time to diagnosis, and treatment access are influenced by multiple factors [ 12 ]. Ongoing epidemiologic research and the advancement of a deeper understanding of ASD are critical to the development of effective prevention, diagnosis, and interventions.

Historical background

Early history of research and diagnosis of asd.

The concept of ASD was first clearly defined in the 1940s, when a group of children exhibiting extreme self-isolation and lack of responsiveness to the environment was first described by American psychiatrist Leo Kanner [ 13 ]. Almost simultaneously, Austrian child psychologist Hans Asperger described a similar but higher level of functioning in a condition that came to be known as Asperger’s syndrome [ 14 ]. These two independent studies laid the foundation for the modern understanding of ASD. For the first few decades, ASD was considered extremely rare and was often confused with schizophrenia. Due to a lack of in-depth understanding of ASD, early diagnostic criteria were unclear and treatment was largely limited to behavioral interventions and psychotherapy. Over time, researchers began to pay more attention to the genetic and neurobiological underpinnings of ASD, thus contributing to a more comprehensive understanding of this complex condition. Since the 1990s, the diagnosis of ASD has risen significantly, as diagnostic criteria have continued to be refined and public awareness has increased. This period has also witnessed an increased awareness of the importance of early diagnosis and intervention for ASD, which has led to significant improvements in the prognosis and quality of life for many children and adults with ASD [ 15 ].

Evolution of research paradigms

The research paradigm for ASD has undergone a remarkable evolution since the mid-twentieth century, a process that reflects a deepening of the understanding of ASD as well as advances in scientific research methods [ 16 ]. In the early stages, ASD research focused on behavioral observations and psychoanalysis, when ASD was often mistaken for an emotional disorder due to an indifferent mother. During this period, understanding of ASD was relatively limited and treatments focused primarily on psychotherapy and behavior modification. Into the second half of the twentieth century, with advances in genetics and neuroscience, researchers began to explore the biological basis of ASD. This marked a shift from a psychosocial to a biomedical model, and the focus of research gradually shifted to genetic factors and abnormalities in brain structure and function. Through a large number of family and twin studies, scientists found that ASD has a high genetic predisposition, while neuroimaging studies revealed the specificity of brain development in ASD patients. In the twenty-first century, with the application of bioinformatics and high-throughput gene sequencing technology, the study of ASD has entered a new stage [ 17 ]. Researchers have not only been able to identify specific genetic variants associated with ASD, but have also begun to explore the interaction between environmental factors and genetic susceptibility. In addition, the adoption of interdisciplinary research approaches, such as combining neuroscience, genetics, psychology, and computational modeling, has provided new perspectives for understanding the complexity of ASD.

Recently, the concepts of precision medicine and personalized treatment strategies have been introduced to the study of ASD, aiming to develop customized intervention programs based on each patient’s genetic background and symptom profile. With advances in technology and improved methods of data analysis, future research on ASD is expected to reveal more knowledge about its pathomechanisms and provide more effective support and treatment for patients with ASD.

Etiologic studies

Genetic factors, monogenic genetic cases.

The etiology of ASD is multifactorial, involving a complex interaction of genetic and environmental factors. Although most cases of ASD are thought to be the result of polygenic interactions, there are some cases that are directly associated with variations in a single gene, and these are referred to as monogenic genetic cases. Monogenic genetic cases provide an important window into understanding the genetic basis of ASD, although they represent a relatively small proportion of all ASD cases [ 18 ]. A number of specific genetic syndromes, such as fragile X syndrome, tuberous sclerosis, 15q11-q13 duplication syndrome, and Rett syndrome, have been found to be associated with a higher risk of ASD. These conditions, often caused by mutations or abnormalities in a single gene, can lead to significant differences in brain development and function, thereby increasing the probability of an ASD phenotype. Fragile X syndrome is one of the most common forms of inherited intellectual disability and the single-gene disorder known to be most strongly associated with ASD. It is caused by a repeat expansion on the FMR1 gene [ 19 ]. Tuberous sclerosis (TSC) is an inherited disorder that affects multiple systems and is caused by mutations in the TSC1 or TSC2 genes, and the prevalence of ASD is higher in patients with TSC. 15q11-q13 duplication syndrome (Dupuy 15q syndrome) involves a region of chromosome 15, the duplication of which is associated with an increased risk of ASD [ 20 ]. Rett syndrome, which predominantly affects females, is caused by mutations in the MECP2 gene, and patients often exhibit some of the features of ASD, such as impaired social interactions [ 21 ]. The association of these classical candidate genes with ASD is summarized in Table  1 .

The discovery of these monogenic genetic cases is not only crucial for understanding the genetic mechanisms of ASD, but also potentially valuable for the development of interventional and therapeutic strategies targeting specific genetic variants. However, even in these cases, the expression of the genetic variants showed a degree of heterogeneity, suggesting that the diversity of phenotypic features and clinical manifestations, even in monogenic genetic cases, may be influenced by other genetic and environmental factors. Therefore, an in-depth study of these conditions will not only improve our understanding of the genetic basis of ASD, but also provide clues for the development of more personalized therapeutic strategies.

Multigene interactions

The development of ASD is widely recognized as a result of the interaction of genetic and environmental factors, with polygenic interactions occupying a central position in the genetic background of the disease. Unlike monogenic cases, polygenic interactions involve variants or polymorphisms in multiple genes that together increase the risk of ASD. These genetic variants may contribute a smaller effect in each individual, but when acting together they can significantly increase the probability of ASD development [ 30 ]. Current research suggests that no single gene can explain all cases of ASD. Instead, hundreds of genetic loci have been identified that are associated with an increased risk of ASD. These genes are often involved in key processes such as brain development, neuronal signaling, and intercellular communication, suggesting that ASD involves extensive regulation of brain function and structure. The complexity of multigene interactions means that genetic studies of ASD require large-scale genomic data and sophisticated statistical methods to reveal those genomic variants that increase risk.

Meta-analyses of large-sample genome-wide association studies (GWAS) have identified several consistently replicated ASD risk gene loci, such as those in the chromosomal regions 3p21, 5p14, 7q35, and 20p12. These loci contain genes like CNTN4, CNTNAP2, and NRXN1, which play crucial roles in neurodevelopment and synaptic function, particularly in processes such as synaptic adhesion and neurotransmission. These findings provide a more robust understanding of the genetic architecture of ASD and highlight the importance of integrating genetic findings with functional studies to advance our understanding of the disorder. They also have implications for future research, such as the development of personalized diagnostic and therapeutic strategies based on an individual's genetic profile. Through genome-wide association studies (GWAS) and other genomic approaches, scientists are gradually unraveling the genetic landscape of this complex disease. Understanding the impact of multiple gene interactions on ASD not only helps us understand its genetic basis, but also opens up the possibility of developing personalized treatment and intervention strategies [ 31 ].

Environmental factors

Maternal exposure.

Exposure during pregnancy refers to a mother’s exposure to specific environmental factors or substances during fetal development, which may increase the child's risk of developing ASD in the future. These exposures include certain prescription medications (e.g., anti-seizure medications and opioids), environmental pollutants (e.g., heavy metals and air pollutants), infections (e.g., rubella and influenza viruses), and poor nutrition or deficiencies in specific nutrients (e.g., folic acid). These factors may increase the risk of ASD by affecting fetal brain development and the maturation process of the nervous system. Understanding the effects of exposure during pregnancy can help to take preventive measures to reduce the incidence of ASDs [ 32 ].

Effects of early developmental stages

The early developmental stages of ASD are influenced by a variety of factors that include genetic predisposition, environmental exposures, and early life experiences. During a child's early development, the brain experiences rapid growth and the formation of neural networks. Any disruption during this critical period may interfere with the proper development of brain structure and function, thereby increasing the risk of ASD. For example, very early lack of social interaction, delayed language development or abnormal sensory processing may be early signs of ASD. These developmental abnormalities reflect difficulties in the brain’s nervous system in processing information, making connections and adapting to environmental changes. Early identification and intervention are essential to promote optimal development in children with ASD [ 33 ].

Genetic–environmental interactions

The genetic–environmental interactions are summarized in Fig.  1 . ASD develops as a result of the interaction between genetic and environmental factors, and this interaction reflects the complexity of the combination of genetic background and external environmental factors that influence ASD risk. Specifically, certain genetic susceptibilities may be activated in response to environmental triggers, leading to the development of ASD. For example, genetic variants may make individuals more sensitive to certain environmental exposures (e.g., substance use during pregnancy, environmental pollutants, or maternal nutritional status), which together may increase the risk of ASD by acting on key brain developmental stages [ 34 ]. This complex genetic–environmental interaction underscores the need to understand multifactorial etiological models of ASD and the importance of developing personalized intervention strategies.

Advances in diagnostic methods

Traditional diagnostic methods.

Traditional diagnostic methods for ASD rely heavily on detailed assessments of behavior and developmental history. These assessments are usually conducted by specialized health care providers such as pediatricians, neuropsychologists, or psychiatrists. The diagnostic process encompasses direct observation of the child as well as in-depth interviews with parents or caregivers to gather information about the child's social interactions, communication skills, and behavioral patterns [ 35 ]. Diagnostic tools include, but are not limited to, the Childhood Autism Rating Scale (CARS), the Autism Diagnostic Observation Scale (ADOS), and the Autism Diagnostic Interview-Revised (ADI-R). These tools are designed to identify core symptoms of ASD, such as social communication deficits and repetitive behaviors or interests. In addition, the doctor may perform a series of developmental or cognitive assessments to rule out other conditions that may explain the child’s behavior, such as language disorders or other neurodevelopmental disorders [ 36 ]. While these traditional diagnostic methods are highly effective in recognizing ASD, they rely on subjective assessments and the experience of the professional, and therefore may have some degree of variability. In recent years, with a deeper understanding of ASDs, new diagnostic techniques and methods are being developed and adopted to improve diagnostic accuracy and efficiency.

Latest diagnostic techniques and tools

Genetic testing.

Genetic testing for ASD is a method of identifying risks associated with ASD by analyzing genetic variants in an individual's DNA. This testing looks for specific genetic variants that have been linked by scientific research to the development of ASD. Although the genetic background of ASD is extremely complex, involving multiple genes and the interaction of genes with environmental factors, variants in specific genes have been identified as having a significant impact on ASD risk [ 37 ]. For example, variants in the SHANK3 gene are associated with Phelan–McDermid syndrome, and patients with this syndrome often exhibit ASD features. Variants in the FMR1 gene are responsible for fragile X syndrome, which is the most common single-gene cause of ASD known to be associated with ASD. Mutations in the MECP2 gene have been associated with Rett syndrome, and patients with Rett syndrome often exhibit ASD condition. In addition, variants in the NRXN1 and NLGN3/4 genes have been found to increase the risk of ASD [ 38 ]. Genetic testing can help provide more precise diagnostic information, and in those cases of ASD where the cause is unknown, it may even reveal the underlying genetic cause. This will not only help to understand the genetic mechanisms of ASD, but also provide more targeted intervention and support strategies for patients and families.

Neuroimaging

Neuroimaging techniques in the study of ASD provide a non-invasive way to explore changes in brain structure and function, helping scientists better understand the biological basis of ASD. These techniques include functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and positron emission tomography (PET). Through these neuroimaging techniques, researchers are able to observe structural and functional differences in specific regions and networks of the brain in individuals with ASD [ 39 ]. For example, fMRI can reveal patterns of brain activity when performing specific tasks, helping to understand the impairments in social, language, and cognitive functioning in individuals with ASD. dTI focuses on the microstructure of the brain’s white matter, revealing the connections of bundles of nerve fibers, which can help to study neural connectivity issues in ASD. PET scans, on the other hand, are able to assess the activity of specific chemicals in the brain, providing clues to study the neurochemical basis of ASD [ 40 ]. With these advanced neuroimaging techniques, researchers will not only be able to delve deeper into the neurodevelopmental abnormalities of ASD, but also identify possible novel therapeutic targets that can provide a scientific basis for developing more effective interventions. However, while these techniques provide valuable perspectives in understanding ASD, a complete understanding of the complexity of the brain remains a challenge for future research.

Early screening methods

Recently, the field of early screening for ASD has witnessed the application of a number of innovative techniques designed to improve the accuracy and convenience of screening. One notable new approach is the use of artificial intelligence (AI) and machine learning techniques to analyze children's behavioral videos and biomarkers. By training algorithms to recognize specific behavioral patterns and physiological signals associated with ASD, these technologies can help physicians and researchers identify potential ASD symptoms earlier [ 41 ]. Another area of innovation is eye-tracking technology, which assesses children’s social and cognitive development by analyzing their eye movement patterns when viewing pictures or videos. Studies have shown that the eye movement patterns of children with ASD while viewing social scenes differ from those of typically developing children, providing a non-invasive window for early screening [ 42 ]. The application of these state-of-the-art technologies not only improves the efficiency and accessibility of early screening, but also provides new perspectives for understanding the complexity and individual differences in ASD [ 43 ]. Although these approaches are still in the research and development stage, they demonstrate the great potential of utilizing technological advances to improve the process of ASD screening and diagnosis. With further validation and refinement of these techniques, it is expected that they will make a significant contribution to the early identification and intervention of ASD in the future.

Treatment approaches and intervention strategies

Behavioral and educational interventions, applied behavior analysis (aba).

Applied behavior analysis (ABA) is an intervention approach based on the principles of behavioral psychology that is widely used in the treatment of children with autism spectrum disorders (ASD). ABA works to understand and improve specific behaviors, particularly to enhance social, communication, academic skills, and daily living skills, while reducing maladaptive behaviors. It helps individuals learn new skills and behaviors by systematically applying reinforcement strategies that encourage and reward desired behaviors [ 44 ]. ABA therapy is highly individualized and customized to each child’s specific needs and abilities. Treatment planning begins with a detailed behavioral assessment to identify target behaviors and intervention strategies. Learned behaviors are then reinforced and cemented through one-on-one teaching sessions using positive reinforcement. ABA also emphasizes the importance of data, which is collected and analyzed on an ongoing basis by the therapist to monitor progress and adjust the treatment plan as necessary [ 45 ]. Research has shown that ABA is an effective way to improve social interactions, communication skills, and learning in children with ASD. Through early and consistent intervention, ABA can significantly improve the independence and overall quality of life of children with ASD. Although ABA treatment requires a commitment of time and resources, the long-term benefits it brings to children with ASD and their families are immeasurable.

Social skills training

Social skills training (SST) for children with autism spectrum disorders (ASD) is an intervention designed to improve their ability to interact socially in everyday life. This training focuses on teaching children with ASD the ability to understand social cues, establish effective communication skills, and develop friendships. Through SST, children learn how to recognize and interpret other people's facial expressions, body language, and social etiquette, which are essential for building positive relationships [ 46 ]. Social skills training typically includes a series of structured instructional activities such as role-playing, social stories, interactive group exercises, and peer modeling. These activities are designed to provide practice in real-world social situations in a supportive and interactive manner, helping children with ASD learn and practice new skills in a safe environment [ 47 ]. In addition, SST can include teaching emotion management and conflict resolution skills to help children with ASD better understand and express their emotions and cope with challenges in social interactions. Through regular and consistent practice, children with ASD can improve their self-confidence, increase their social engagement, and ultimately improve their social competence and quality of life. SST has been shown to be significantly effective in enhancing social adjustment and interpersonal interactions in children with ASD [ 48 ].

Medical treatment

While there is no cure for ASD, certain medications can be used to manage specific symptoms associated with ASD, such as behavioral problems, attention deficits, anxiety, and mood swings that are common in individuals with autism. Medication is often used as part of a comprehensive intervention program designed to improve the quality of life and daily functioning of the patient [ 49 ]. Medications commonly used for ASD symptom management include antipsychotics, antidepressants, stimulants, and anxiolytics. For example, two antipsychotics, risperidone and aripiprazole, have been approved by the FDA for the treatment of stereotypic and aggressive behavior in children and adolescents with ASD. In addition, selective serotonin reuptake inhibitors (SSRIs) may be helpful in managing anxiety and depressive symptoms in individuals with ASD.

Importantly, medication needs to be closely monitored by a physician to ensure the effectiveness and safety of the medications, as they may have side effects. We have summarized the research evidence on the efficacy and safety of commonly used medications in ASD, including antipsychotics for treating irritability and aggression, antidepressants for co-occurring anxiety and depression, and other medications such as stimulants and melatonin. While these medications can be helpful in managing specific symptoms, they also carry potential side effects and risks, such as weight gain, metabolic disturbances, and behavioral activation. Therefore, a thorough diagnostic evaluation, individualized treatment planning, close monitoring, and regular follow-up are essential when considering pharmacotherapy for individuals with ASD. The decision to medicate should be based on an individualized assessment that takes into account the patient’s specific needs, the severity of symptoms, and possible side effects. At the same time, pharmacological treatments are often used in combination with non-pharmacological treatments such as behavioral interventions and educational support to achieve optimal therapeutic outcomes [ 50 ].

Biofeedback and neuromodulation

Biofeedback and neuromodulation are innovative approaches that have been explored in recent years in the treatment of ASD, aiming to reduce ASD symptoms by improving brain function. Biofeedback techniques enable individuals to learn how to control physiological processes that are not normally under conscious control, such as heart rate, muscle tension, and brainwave activity. Through real-time feedback, patients can learn how to regulate their physiology, resulting in improved concentration, reduced anxiety, and improved emotional regulation. Neuromodulation, specifically transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), affects neural activity in the brain through external stimulation. tMS utilizes a magnetic field to affect neuronal activity in specific areas of the brain, while tDCS modulates neuronal excitability by applying a weak electrical current. These methods have been studied for improving social communication skills and reducing stereotypical behaviors in people with ASD [ 51 ].

Biofeedback helps individuals develop self-regulation skills by providing real-time feedback on physiological states, while neuromodulation techniques like TMS and tDCS modulate cortical excitability and neural plasticity in aberrant circuits implicated in ASD. Current research suggests potential benefits of these techniques in improving emotional regulation, social functioning, and cognitive performance, but mixed results highlight the need for larger, well-controlled trials to validate efficacy, safety, and optimal protocols. Despite challenges, these techniques show promise as adjunctive therapies in the comprehensive management of ASD, warranting further research to guide their translation into clinical practice. Although biofeedback and neuromodulation show potential in the treatment of ASD, research on these techniques is currently in its infancy. More clinical trials and studies are needed to evaluate their effectiveness, safety, and long-term effects and to determine which patients may benefit from these interventions. Nevertheless, as non-pharmacologic treatments, they offer promising complementary options to the comprehensive treatment of ASD.

Emerging intervention approaches

Technology-assisted interventions.

Technology-assisted interventions have become an important development in the field of ASD treatment in recent years, providing new ways for children with ASD to learn and communicate. These interventions utilize computers, tablets, smartphone apps, and virtual reality technology to design a range of interactive learning tools and games designed to improve social skills, communication, and cognitive functioning in children with ASD [ 52 ]. A key advantage of technology-assisted interventions is their ability to provide highly personalized learning experiences. Software and applications can be adapted to a child's specific needs and interests, ensuring that learning content is both engaging and appropriate to the individual's developmental level. In addition, the feedback provided by technology is often immediate and consistent, helping children with ASD to better understand and process information. The use of virtual reality technology, by simulating social situations, provides a safe and controlled environment for children with ASD to practice social interaction and problem-solving skills, which is often difficult to achieve in traditional educational and therapeutic settings [ 53 ]. Although technology-assisted interventions have demonstrated great potential, research on their long-term effects and optimal implementation is still ongoing. To maximize the benefits of these tools, it is often recommended that technology-assisted interventions be used in conjunction with other therapeutic approaches to provide a comprehensive intervention program.

Diet and nutrition interventions

Dietary and nutritional interventions have received increasing attention in the treatment of ASD, based on the observed potential link between nutritional imbalances and ASD symptoms. This intervention approach aims to improve the behavioral performance and overall health of children with ASD by optimizing their diet. Specific strategies include restricting certain foods that may exacerbate symptoms, such as gluten and lactose, as well as increasing intake of foods rich in essential nutrients to support brain development and function [ 54 ]. Several studies support the potential benefits of specific dietary interventions, such as implementing a gluten-free lactose-free (GFCF) diet, which may help improve behavioral and digestive symptoms in some children with ASD. In addition, supplementation with omega-3 fatty acids, vitamins, and minerals (e.g., magnesium and zinc) have been proposed as potentially beneficial strategies to support neurologic health and alleviate ASD-related symptoms [ 55 ]. However, the effectiveness of dietary and nutritional interventions may vary by individual and more scientific research is needed to gain a deeper understanding of their long-term effects on children with ASD. Before implementing any dietary intervention, it is recommended to consult with a physician or nutritional expert to ensure that the individual needs of the child are met and to avoid malnutrition. In combination, dietary and nutritional interventions can be used as part of a comprehensive treatment plan for ASD, complementing traditional behavioral and educational interventions.

Social and educational integration

Educational integration of children with asd.

Educational integration of children with ASD is an inclusive educational practice that seeks to integrate children with ASD into the mainstream educational system to learn and grow with their typically developing peers. This integration model emphasizes individualized learning plans and adaptive teaching strategies to meet the unique needs of children with ASD while promoting their social inclusion and emotional development. Through educational integration, children with ASD are provided with opportunities to interact with other children, which is essential for them to learn social skills, enhance their communication abilities, and improve their ability to adapt to society. To support the successful integration of children with ASD, schools often provide special education services such as speech and language therapy, occupational therapy, and behavioral interventions, which take place in classroom settings to ensure their academic and social progress. Educational inclusion is not only beneficial for children with ASD, but it also helps to foster a sense of inclusion and diversity among their peers. By learning and playing together, all children learn to respect and understand differences, laying the foundation for a more inclusive society. However, effective integrated education requires close collaboration among teachers, parents and professionals, as well as the availability of appropriate resources and support systems [ 56 ].

Social integration and employment of adults with ASD

The social integration and employment of adults with ASD is a current focus of attention in ASD research and social services. For many adults with ASD, social integration challenges include establishing stable relationships, participating in community activities, and finding and keeping a job. Although adults with ASD may have unique skills and interests in specific areas, social communication deficits and fixed patterns of behavior may make it difficult for them in traditional work settings. In recent years, more and more organizations and businesses have begun to recognize the value of diversity and inclusion and are working to create work environments that are better suited for adults with ASD. This includes providing flexible work arrangements, clear communication guidelines, and individualized support measures such as workplace co-worker support and professional career counseling. In addition, social service programs and non-profit organizations offer training and job readiness programs specifically designed for adults with ASD to help them develop necessary vocational skills and social competencies. Through these efforts, adults with ASD will not only be able to find jobs that meet their interests and abilities, but also find a place for themselves in society, enhancing their independence and life satisfaction. However, the realization of this goal requires sustained social awareness-raising and the construction of an ASD-friendly environment [ 57 ].

Future research directions

Application of precision medicine in asd treatment.

The application of precision medicine in the treatment of ASD represents a paradigm of a personalized treatment strategy that aims to tailor the treatment plan to each patient's genetic information, biomarkers, history of environmental exposure, and lifestyle factors. The philosophy behind this approach is that, although ASD is classified as a spectrum, each patient's etiology, symptoms, and their severity are different, and therefore treatment should be highly individualized [ 58 , 59 ]. By fully sequencing a patient's genome, scientists and physicians can identify specific genetic variants that may affect ASD symptoms, allowing them to develop targeted treatments. For example, if a particular ASD patient's symptoms are linked to an abnormality in a specific metabolic pathway, that pathway could be modulated through dietary adjustments, nutritional supplements, or specific medications with a view to improving symptoms. In addition, precision medicine involves the consideration of environmental factors and personal behavior to ensure that treatment options are not only scientifically effective, but also appropriate to the patient's lifestyle. Although precision medicine is still in its early stages in the field of ASD, it offers great potential for delivering more personalized and effective treatment regimens, which are expected to significantly improve the quality of life of people with ASD [ 60 ].

Prospects for emerging biotechnologies

Emerging biotechnologies in the field of ASD, such as gene editing, stem cell therapies, and biomarker development, are opening up new possibilities for treating and understanding ASD. Gene editing technologies, particularly the CRISPR-Cas9 system, provide researchers with the means to precisely modify genetic variants associated with ASD, promising to reveal how specific genetic variants affect brain development and function, thereby providing clues for the development of targeted therapies [ 61 ]. Stem cell therapies utilize a patient's own induced pluripotent stem cells (iPSCs) to study the pathomechanisms of ASD by mimicking the neurodevelopmental process in vitro, as well as exploring potential cellular alternative treatments. In addition, the discovery of biomarkers facilitates early diagnosis and monitoring of disease progression, making personalized treatment possible [ 62 ]. In addition, induced pluripotent stem cell (iPSC)-derived brain organoids from ASD patients have emerged as a powerful tool for studying the neurodevelopmental abnormalities associated with ASD. These 3D, self-organizing models recapitulate key features of human brain development in vitro, allowing researchers to investigate the cellular and molecular mechanisms underlying ASD pathogenesis. By comparing brain organoids derived from ASD patients with those from healthy controls, researchers can identify alterations in neuronal differentiation, migration, and connectivity that may contribute to the development of ASD. Moreover, patient-derived brain organoids provide a personalized platform for drug screening and testing, enabling the identification of targeted therapies that can be tailored to an individual's genetic background. This approach has the potential to revolutionize the development of precision medicine strategies for ASD, by providing a more accurate and relevant model system for investigating disease mechanisms and testing novel therapeutic interventions. As the field continues to advance, iPSC-derived brain organoids are expected to play an increasingly important role in unraveling the complex etiology of ASD and guiding the development of personalized treatment strategies [ 63 ]. The development of these technologies has not only improved our understanding of the complex etiology of ASD, but also provided more precise and effective treatment options for ASD patients. Although most of these emerging biotechnologies are still in the research phase, they bring hope and anticipation for the future of ASD treatment and management. As research progresses and technology matures, it is expected that these innovative approaches will bring substantial benefits to individuals with ASD and their families.

Interaction between social policy and ASD research

The interaction between social policy and ASD research is key to achieving better social inclusion and quality of life for individuals with ASD and their families. Effective social policies can provide the necessary financial support and legal framework for ASD research, promoting a deeper understanding of ASD and the development of new treatments. For example, policies can promote collaboration in interdisciplinary research, encourage the use of innovative technologies and methods, and support long-term follow-up studies. In addition, social policies play a crucial role in ensuring that ASD research results are translated into practical applications and that education, employment, and social services are provided to individuals with ASD. Through the development of inclusive education policies, employment assistance programs, and the provision of integrated social services, policies can help individuals with ASD realize their potential and better integrate into society. At the same time, advances in ASD research also provide a scientific basis for the development of more targeted and effective social policies, helping policymakers understand the needs of individuals with ASD and develop more precise support measures. Thus, there is a close interplay between social policy and ASD research, which together have contributed to the advancement of the understanding of ASD and coping strategies.

Limitations of the current research

Although significant progress has been made in ASD research, a number of key limitations remain. First, the etiology of ASD is extremely complex, involving genetic and environmental factors and their interactions, making it extremely challenging to identify specific etiologies and develop targeted treatment strategies. Second, the heterogeneity of ASD is reflected in the extreme variability of symptoms among patients, which makes it difficult to develop uniform diagnostic criteria and treatment approaches. In addition, most studies have focused on children, and adult patients with ASD have been relatively understudied, which limits the understanding of the full lifespan of ASD. In terms of research methodology, most current ASD research relies on small, short-term studies, which may affect the broad applicability of results and the assessment of long-term effectiveness. In addition, although advances in technology have provided new tools for ASD diagnosis and intervention, the popularization and application of these technologies still face economic and resource constraints. Finally, ASD research is unequal across the globe, with far more research conducted in resource-rich countries and regions than in resource-limited areas. This imbalance limits a comprehensive understanding of ASD in different cultural and social contexts. Therefore, to overcome these limitations, more interdisciplinary, cross-cultural, and long-term research, as well as global collaborations, are needed to deepen the understanding of ASD and improve the quality of life of individuals with ASD.

Perspectives on future research

The outlook for future prevention and treatment of ASD points in a more individualized, integrated, and technology-driven direction. With a deeper understanding of the genetic and environmental factors of ASD, it is expected that more targeted interventions and therapeutic strategies will be developed that will be based on an individual's specific genetic background and pathologic characteristics. The application of precision medicine is expected to improve treatment outcomes, reduce unwanted side effects, and optimize resource allocation. Meanwhile, technological advances, particularly artificial intelligence, machine learning, and virtual reality, are expected to revolutionize the way ASDs are diagnosed, monitored, and treated. These technologies are capable of delivering customized learning and treatment programs that enhance the acceptability and effectiveness of interventions. In addition, interdisciplinary research will be strengthened, and social policies and public health strategies will focus more on early screening and intervention, as well as increasing public awareness and understanding of ASD. Most importantly, the future of ASD prevention and treatment will place greater emphasis on the needs of patients and families, promote social integration and employment of patients, and improve their quality of life. As society's awareness of diversity and inclusion increases, individuals with ASD will receive more support and respect and enjoy fuller opportunities for social participation.

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Authors and affiliations.

Department of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China

Lei Qin, Wenjing Ning & Mengmeng Cui

Department of Intensive Care Medicine, Feicheng People’s Hospital, Taian, Shandong, China

Haijiao Wang

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Autism Spectrum Disorder : A Review

• 1 Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco
• Special Communication Screening for Autism Spectrum Disorder in Young Children Albert L. Siu, MD, MSPH; and the US Preventive Services Task Force (USPSTF); Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Linda Ciofu Baumann, PhD, RN, APRN; Karina W. Davidson, PhD, MASc; Mark Ebell, MD, MS; Francisco A. R. García, MD, MPH; Matthew Gillman, MD, SM; Jessica Herzstein, MD, MPH; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH JAMA
• JAMA Patient Page Screening for Autism Spectrum Disorder Jill Jin, MD, MPH JAMA
• JAMA Patient Page Patient Information: Autism Spectrum Disorder Rebecca Voelker, MSJ JAMA
• Review The Emerging Clinical Neuroscience of Autism Spectrum Disorder Rebecca A. Muhle, MD, PhD; Hannah E. Reed, MD; Katharine A. Stratigos, MD; Jeremy Veenstra-VanderWeele, MD JAMA Psychiatry
• Original Investigation Association of Allergies With Autism Spectrum Disorder Guifeng Xu, MD; Linda G. Snetselaar, PhD; Jin Jing, MD, PhD; Buyun Liu, MD, PhD; Lane Strathearn, MBBS, FRACP, PhD; Wei Bao, MD, PhD JAMA Network Open
• Research Letter Racial and Ethnic Differences in Rates and Age of Diagnosis of Autism Spectrum Disorder Hoangmai H. Pham, MD, MPH; Neil Sandberg, MS; Jeff Trinkl, MD; Johnston Thayer, MBA, RN JAMA Network Open
• Original Investigation Concordance of Diagnosis of ASD Made by Pediatricians vs a Multidisciplinary Specialist Team Melanie Penner, MSc, MD; Lili Senman, MA; Lana Andoni, MSc; Annie Dupuis, PhD; Evdokia Anagnostou, MD; Shawn Kao, MD; Abbie Solish, PhD; Michelle Shouldice, MEd, MD; Genevieve Ferguson, MEd; Jessica Brian, PhD JAMA Network Open
• Original Investigation Association Between Autism Spectrum Disorders and Cardiometabolic Diseases Chathurika S. Dhanasekara, MD, MS, PhD; Dominic Ancona, M-PAS; Leticia Cortes, M-PAS; Amy Hu, M-PAS; Afrina H. Rimu, MD, MS; Christina Robohm-Leavitt, M-PAS, DMSc; Drew Payne, DO; Sarah M. Wakefield, MD; Ann M. Mastergeorge, PhD; Chanaka N. Kahathuduwa, MD, MPhil, PhD JAMA Pediatrics

Importance   Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD.

Observations   The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child’s first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child’s behavior and semistructured caregiver interview focused on the individual’s development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep.

Conclusions and Relevance   ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.

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Title: mcdgln: masked connection-based dynamic graph learning network for autism spectrum disorder.

Abstract: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by complex physiological processes. Previous research has predominantly focused on static cerebral interactions, often neglecting the brain's dynamic nature and the challenges posed by network noise. To address these gaps, we introduce the Masked Connection-based Dynamic Graph Learning Network (MCDGLN). Our approach first segments BOLD signals using sliding temporal windows to capture dynamic brain characteristics. We then employ a specialized weighted edge aggregation (WEA) module, which uses the cross convolution with channel-wise element-wise convolutional kernel, to integrate dynamic functional connectivity and to isolating task-relevant connections. This is followed by topological feature extraction via a hierarchical graph convolutional network (HGCN), with key attributes highlighted by a self-attention module. Crucially, we refine static functional connections using a customized task-specific mask, reducing noise and pruning irrelevant links. The attention-based connection encoder (ACE) then enhances critical connections and compresses static features. The combined features are subsequently used for classification. Applied to the Autism Brain Imaging Data Exchange I (ABIDE I) dataset, our framework achieves a 73.3\% classification accuracy between ASD and Typical Control (TC) groups among 1,035 subjects. The pivotal roles of WEA and ACE in refining connectivity and enhancing classification accuracy underscore their importance in capturing ASD-specific features, offering new insights into the disorder.

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How parents and caregivers can evaluate the research on MERT and other potential autism treatments

by Corinne Purtill, Los Angeles Times

As diagnoses of autism spectrum disorder have increased in the last two decades, so have the number of experimental and off-label therapies seeking to address the condition.

For parents navigating the complex and often contradictory landscape of autism interventions—while also balancing medical appointments, educational specialists and countless other family needs—evaluating these treatments can be daunting.

Experts in autism research talked to The Times about what parents and patients should watch for when evaluating a potential new treatment—for autism or any other condition.

Take testimonials with a grain of salt

Firsthand accounts of a therapy's life-changing effects can be powerfully compelling. But such stories alone can't indicate how effective a treatment will be for anyone else, autism experts said.

"Be wary of therapies that are sold to you with testimonials. If you go to a clinic website and they have dozens of quotes from parents saying 'This changed my child's life in XYZ ways,' that isn't the same as evidence," said Zoe Gross of the Autistic Self Advocacy Network, a nonprofit group run by and for autistic adults.

"If the main way something's advertised is through testimonials, it may be because there isn't research, or what research was done showed it wasn't effective."

Without accompanying data, there is no way to know whether any patient's experience with a treatment is typical or an outlier. A therapy could have only a 1% success rate, Gross said, and still yield dozens of positive outcomes once thousands of people have tried it.

Former patient stories can be a starting point for an exploration of whether a therapy is right for someone, doctors said, but the exploration shouldn't end there.

"There's an old saying in medicine," said Dr. Andrew Leuchter, director of UCLA's TMS Clinical and Research Service. "The plural of anecdote is not data."

Look for—and at—the research

"Right now, it's really sexy to call yourself 'evidence-based,'" said Dr. David Celiberti, executive director of the nonprofit Assn. for Science in Autism Treatment. "For a consumer, that's amazing. You hear 'evidence-based' and of course, you're going to be drawn to it. But people are using that term very loosely."

In the case of magnetic e-resonance therapy, or MERT, its developer Wave Neuroscience features on its website a library of research. Similar links feature on the sites of many licensee clinics.

Most of the publications related to autism cited by MERT clinics—and, at times, by Wave—are either limited in scope or only tangentially related to the therapy, a half-dozen experts said, including some whose work is cited.

One of them, for example, is a brief 2016 article from the Austin Journal of Autism and Related Disabilities titled "The Potential of Magnetic Resonant Therapy in Children with Autism Spectrum Disorder."

Its authors and advisors said they were surprised to learn the paper was being used to advertise the treatment. The paper contains no data or original research and concludes only that MERT could be studied further as an autism therapy without risk of serious harm.

"This isn't an evidence-based paper. It's an opinion piece about the possibilities of this technology," said Dr. John Crawford, a neurologist at Children's Hospital of Orange County and a co-author of the paper. "It's not that impactful from a scientific perspective."

Who else has verified these findings?

Many MERT clinics feature a 2014 electronic poster presentation that examines data from the charts of 141 children who received transcranial magnetic stimulation , the therapy on which MERT is based, for autism.

Until March, Wave featured the poster on its website and highlighted that 59.1% of 44 participants who completed 12 months of treatment improved their scores on the Childhood Autism Rating Scale, an assessment tool used to gauge symptom severity.

A closer look at the report shows that after five days of treatment, 38 patients were dropped from the analysis because their symptoms either showed no improvement or worsened. One had a seizure during treatment.

The authors excluded dozens more patients for various reasons. Of the remaining 44 patients, 26 saw improvement while getting the treatment. That was 59.1% of those remaining, as the poster said, but only 18.4% of the total study population.

The write-up also notes that many of those 26 children were receiving other therapies at the same time that may have been responsible for some or all of the improvements.

Posters are typically prepared as a way to highlight findings at professional conferences and "cannot be interpreted as having undergone rigorous peer review," said USC neurosurgeon Dr. Charles Liu, a co-author on the poster who is not affiliated with Wave or any MERT clinics.

"The main point of the abstract is and remains that more rigorous studies must [be] done."

If research shows changes, how do you know the therapy caused it?

Wave and licensees also highlight a 2022 paper by a technician at a licensee clinic in Australia who is also a doctoral candidate at Australia's University of the Sunshine Coast.

It looks at data from 28 patients at two MERT clinics in Australia whose brains showed "significant improvement" in their individual alpha frequency waves after treatment.

Although some previous research has found correlations between atypical alpha wave frequency and autism diagnoses, six scientists told The Times that there isn't yet enough evidence to understand how changes in alpha waves affect autistic traits, or any scientific consensus on whether "improvement" in this pattern of brain activity has any meaningful effect on autistic behaviors.

The report is a retrospective chart review, which examines existing data from patients' medical records and is often used to identify interesting outcomes worthy of further study.

By design, it does not include a control group, which is what allows researchers to identify whether any changes they see are related to the variable they are studying. Its authors noted in the paper that findings are preliminary and require further study.

"Because this was not a controlled trial or study, [the cause of the changes] could have been anything including placebo effect, any additional therapies the children were receiving, etc.," said Lindsay Oberman, director of the Neurostimulation Research Program at the National Institute of Mental Health.

Medical research follows a hierarchy of evidence. At the bottom are anecdotes and observations: valid points of information that alone aren't enough to draw broad conclusions from.

Above that are observational studies that collect and analyze preexisting data in a systematic way. And at the top are randomized controlled trials, which are designed to eliminate as much bias as possible from the experiment and ensure that the thing being studied is responsible for any changes observed.

"Families need to know that there is this gold standard for studies—to make sure that something works to help people with autism, it needs to have what's called a randomized controlled trial ," said Alycia Halladay, chief science officer at the Autism Science Foundation.

2024 Los Angeles Times. Distributed by Tribune Content Agency, LLC.

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A Short Review on the Current Understanding of Autism Spectrum Disorders

Hye ran park.

1 Department of Neurosurgery, Seoul National University Hospital, Seoul 03080, Korea.

Jae Meen Lee

Hyo eun moon, dong soo lee.

2 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.

Bung-Nyun Kim

3 Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul 03080, Korea.

Jinhyun Kim

4 Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

Dong Gyu Kim

Sun ha paek.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.

INTRODUCTION

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a lack of social interaction, verbal and nonverbal communication in the first 3 years of life. The distinctive social behaviors include an avoidance of eye contact, problems with emotional control or understanding the emotions of others, and a markedly restricted range of activities and interests [ 1 ]. The current prevalence of ASD in the latest large-scale surveys is about 1%~2% [ 2 , 3 ]. The prevalence of ASD has increased in the past two decades [ 4 ]. Although the increase in prevalence is partially the result of changes in DSM diagnostic criteria and younger age of diagnosis, an increase in risk factors cannot be ruled out [ 5 , 6 ]. Studies have shown a male predominance; ASD affects 2~3 times more males than females [ 2 , 3 , 7 ]. This diagnostic bias towards males might result from under-recognition of females with ASD [ 8 ]. Also, some researchers have suggested the possibility that the female-specific protective effects against ASD might exist [ 9 ].

A Swiss psychiatrist, Paul Eugen Bleuler used the term "autism" to define the symptoms of schizophrenia for the first time in 1912 [ 10 ]. He derived it from the Greek word αὐτὀς (autos), which means self. Hans Asperger adopted Bleuler's terminology "autistic" in its modern sense to describe child psychology in 1938. Afterwards, he reported about four boys who did not mix with their peer group and did not understand the meaning of the terms 'respect' and 'polite', and regard for the authority of an adult. The boys also showed specific unnatural stereotypic movement and habits. Asperger describe this pattern of behaviors as "autistic psychopathy", which is now called as Asperger's Syndrome [ 11 ]. The person who first used autism in its modern sense is Leo Kanner. In 1943, he reported about 8 boys and 3 girls who had "an innate inability to form the usual, biologically provided affective contact with people", and introduced the label early infantile autism [ 12 ]. Hans Asperger and Leo Kanner have been considered as those who designed the basis of the modern study of autism.

Most recently, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) adopted the term ASD with a dyadic definition of core symptoms: early-onset of difficulties in social interaction and communication, and repetitive, restricted behaviors, interests, or activities [ 13 ]. Atypical language development, which had been included into the triad of ASD, is now regarded as a co-occurring condition.

As stated earlier, the development of the brain in individuals with ASD is complex and is mediated by many genetic and environmental factors, and their interactions. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Also, the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development create a pattern of dysfunctional neural networks involved in socioemotional processing. Microstructurally, an altered ratio of short- to long-diameter axons and disorganization of cortical layers are observed. Macrostructurally, MRI studies assessing brain volume in individuals with ASD have consistently shown cortical and subcortical gray matter overgrowth in early brain development. Functionally, resting-state fMRI studies show a narrative of widespread global underconnectivity in socioemotional networks, and task-based fMRI studies show decreased activation of networks involved in socioemotional processing. Moreover, electrophysiological studies demonstrate alterations in both resting-state and stimulus-induced oscillatory activities in patients with ASD [ 14 ].

The well-conserved sets of genes and genetic pathways were implicated in ASD, many of which contribute toward the formation, stabilization, and maintenance of functional synapses. Therefore, these genetic aspects coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics are essential to unraveling the pathogenesis of ASD. The number of genes already discovered in ASD holds the promise to translate the knowledge into designing new therapeutic interventions. Also, the fundamental research using animal models is providing key insights into the various facets of human ASD. However, a better understanding of the genetic, molecular, and circuit level aberrations in ASD is still needed [ 15 ].

Neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Importantly, ASD is accompanied by an atypical path of brain maturation, which gives rise to differences in neuroanatomy, functioning, and connectivity. Although considerable progress has been made in the development of animal models and cellular assays, neuroimaging approaches allow us to directly examine the brain in vivo, and to probably facilitate the development of a more personalized approach to the treatment of ASD [ 16 ].

ASD is not a single disorder. It is now broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction.

Genetic causes including gene defects and chromosomal anomalies have been found in 10%~20% of individuals with ASD [ 17 , 18 ]. Siblings born in families with an ASD subject have a 50 times greater risk of ASD, with a recurrence rate of 5%~8% [ 19 ]. The concordance rate reaches up to 82%~92% in monozygotic twins, compared with 1%~10% in dizygotic twins. Genetic studies suggested that single gene mutations alter developmental pathways of neuronal and axonal structures involved in synaptogenesis [ 20 , 21 , 22 ]. In the cases of related with fragile X syndrome and tuberous sclerosis, hyperexcitability of neocortical circuits caused by alterations in the neocortical excitatory/inhibitory balance and abnormal neural synchronization is thought to be the most probable mechanisms [ 23 , 24 ]. Genome-wide linkage studies suggested linkages on chromosomes 2q, 7q, 15q, and 16p as the location of susceptibility genes, although it has not been fully elucidated [ 25 , 26 ]. These chromosomal abnormalities have been implicated in the disruption of neural connections, brain growth, and synaptic/dendritic morphology [ 27 , 28 , 29 ]. Metabolic errors including phenylketonuria, creatine deficiency syndromes, adenylosuccinate lyase deficiency, and metabolic purine disorders are also account for less than 5% of individuals with ASD [ 30 ]. Recently, the correlation between cerebellar developmental patterning gene ENGRAILED 2 and autism was reported [ 31 ]. It is the first genetic allele that contributes to ASD susceptibility in as many as 40% of ASD cases. Other genes such as UBE3A locus, GABA system genes, and serotonin transporter genes have also been considered as the genetic factors for ASD [ 18 ].

Diverse environmental causative elements including pre-natal, peri-natal, and post-natal factors also contribute to ASD [ 32 ]. Prenatal factors related with ASD include exposure to teratogens such as thalidomide, certain viral infections (congenital rubella syndrome), and maternal anticonvulsants such as valproic acid [ 33 , 34 ]. Low birth weight, abnormally short gestation length, and birth asphyxia are the peri-natal factors [ 34 ]. Reported post-natal factors associated with ASD include autoimmune disease, viral infection, hypoxia, mercury toxicity, and others [ 33 , 35 , 36 ]. Table 1 summarizes the known and putative ASD-related genes and environmental factors contributing to the ASD.

In recent years, some researchers suggest that ASD is the result of complex interactions between genetic and environmental risk factors [ 37 ]. Understanding the interaction between genetic and environmental factors in the pathogenesis of ASD will lead to optimal treatment strategy.

Clinical features and Diagnosis

ASD is typically noticed in the first 3 years of life, with deficits in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures [ 1 ]. Children also manifest with non-specific symptoms such as unusual sensory perception skills and experiences, motor clumsiness, and insomnia. Associated phenomena include mental retardation, emotional indifference, hyperactivity, aggression, self-injury, and repetitive behaviors such as body rocking or hand flapping. Repetitive, stereotyped behaviors are often accompanied by cognitive impairment, seizures or epilepsy, gastrointestinal complaints, disturbedd sleep, and other problems. Differential diagnosis includes childhood schizophrenia, learning disability, and deafness [ 38 , 39 ].

ASD is diagnosed clinically based on the presence of core symptoms. However, caution is required when diagnosing ASD because of non-specific manifestations in different age groups and individual abilities in intelligence and verbal domains. The earliest nonspecific signs recognized in infancy or toddlers include irritability, passivity, and difficulties with sleeping and eating, followed by delays in language and social engagement. In the first year of age, infants later diagnosed with ASD cannot be easily distinguished from control infants. However, some authors report that about 50% of infants show behavioral abnormalities including extremes of temperament, poor eye contact, and lack of response to parental voices or interaction. At 12 months of age, individuals with ASD show atypical behaviors, across the domains of visual attention, imitation, social responses, motor control, and reactivity [ 40 ]. There is also report about atypical language trajectories, with mild delays at 12 months progressing to more severe delays by 24 months [ 40 ]. By 3 years of age, the typical core symptoms such as lack of social communication and restricted/repetitive behaviors and interests are manifested. ASD can be easily differentiated from other psychosocial disorders in late preschool and early school years.

Amygdala and ASD

The frontal and temporal lobes are the markedly affected brain areas in the individuals with ASD. In particular, the role of amygdala in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. The amygdala located the medial temporal lobe anterior to the hippocampal formation has been thought to have a strong association with social and aggressive behaviors in patients with ASD [ 41 , 42 ]. The amygdala is a major component of the limbic system and affective loop of the cortico-striato-thalamo-cortical circuit [ 43 ].

The amygdala has 2 specific functions including eye gaze and face processing [ 44 ]. The lesion of the amygdala results in fear-processing, modulation of memory with emotional content, and eye gaze when looking at human face [ 45 , 46 , 47 ]. The findings in individuals with amygdala lesion are similar to the phenomena in ASD. The amygdala receives highly processed somatosensory, visual, auditory, and all types of visceral inputs. It sends efferents through two major pathways, the stria terminalis and the ventral amygdalofugal pathway.

The amygdala comprises a collection of 13 nuclei. Based on histochemical analyses, these 13 nuclei are divided into three primary subgroups: the basolateral (BL), centromedial (CM), and superficial groups [ 42 ]. The BL group attributes amygdala to have a role as a node connecting sensory stimuli to higher social cognition level. It links the CM and superficial groups, and it has reciprocal connection with the orbitofrontal cortex, anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC) [ 48 ]. The BL group contains neurons responsive to faces and actions of others, which is not found in the other two groups of amygdala [ 49 , 50 ]. The CM group consists of the central, medial, cortical nuclei, and the periamygdaloid complex. It innervates many of the visceral and autonomic effector regions of the brain stem, and provides a major output to the hypothalamus, thalamus, ventral tegmental area, and reticular formation [ 51 ]. The superficial group includes the nucleus of the lateral olfactory tract [ 42 ].

Neurochemistrial studies revealed high density of benzodiazepine/GABAa receptors and a substantial set of opiate receptors in the amygdala. It also includes serotonergic, dopaminergic, cholinergic, and noradrenergic cell bodies and pathways [ 52 ]. Since some patients with temporal epilepsy and aggressive behavior experienced improvement in aggressiveness after bilateral stereotactic ablation of basal and corticomedial amygdaloid nuclei, the role of amygdala in emotional processing, especially rage processing has been investigated [ 53 , 54 , 55 , 56 ]. Some evidences for the amygdala deficit in patients with ASD have been suggested. Post-mortem studies found the pathology in the amygdala of individuals with ASD compared to age- and sex-matched controls [ 57 , 58 , 59 ]. Small neuronal size and increased cell density in the cortical, medial, and central nuclei of the amygdala were detected in ASD patients.

Several studies proposed the use of an animal model to confirm the evidence for the association between amygdala and ASD [ 60 , 61 ]. Despite the limitation which stems from the need to prove higher order cognitive disorder, the studies suggested that disease-associated alterations in the temporal lobes during experimental manipulations of the amygdala in animals have produced some symptoms of ASD [ 62 ]. Especially, the Kluver-Bucy syndrome, which is caused by bilateral damage to the anterior temporal lobes in monkeys, has characteristic manifestations similar to ASD [ 63 , 64 ]. Monkeys with the Kluver-Bucy syndrome shows absence of social chattering, lack of facial expression, absence of emotional reactions, repetitive abnormal movement patterns, and increased aggression. Sajdyk et al. performed experiments on rats and discovered that physiological activation of the BL nucleus of the amygdala by blocking tonic GABAergic inhibition or enhancing glutamate or the stress-associated peptide corticotropin-releasing factor (CRF)-mediated excitation caused reduction in social behaviors [ 65 ]. On the contrary, lesioning of the amygdala or blocking amygdala excitability with glutamate antagonist increased dyadic social interactions [ 60 ]. Besides animals, humans who underwent lesioning of the amygdala showed impairments in social judgment. This phenomenon is called acquired ASD [ 66 , 67 , 68 ]. The pattern of social deficits was similar in idiopathic and acquired ASD [ 69 ]. Felix-Ortiz and Tye sought to understand the role of projections from the BL amygdala to the ventral hippocampus in relation to behavior. Their study using mice showed that the BLS-ventral hippocampus pathway involved in anxiety plays a role in the mediation of social behavior as well [ 70 ].

The individuals with temporal lobe tumors involving the amygdala and hippocampus provide another evidence of the correlation between the amygdala and ASD. Some authors reported that patients experienced autistic symptoms after temporal lobe was damaged by a tumor [ 71 , 72 ]. Also, individuals with tuberous sclerosis experienced similar symptoms including facial expression due to a temporal lobe hamartoma [ 73 ].

Although other researchers failed to find structural abnormalities in the mesial temporal lobe of autistic subjects by performing magnetic resonance imaging (MRI) studies [ 74 , 75 , 76 ], recent development in neuroimaging has facilitated the investigation of amygdala pathology in ASD. Studies using structural MRI estimated volumes of the amygdala and related structures in individuals with ASD and age-, gender, and verbal IQ-matched healthy controls [ 77 ]. Increase in bilateral amygdala volume and reduction in hippocampal and parahippocampal gyrus volumes were noted in individuals with ASD. Also, the lateral ventricles and intracranial volumes were significantly increased in the autistic subjects; however, overall temporal lobe volumes were similar between the ASD and control groups.

There was a significant difference in the whole brain voxel-based scans of individuals with ASD and control groups [ 78 ]. Individuals with ASD showed decreased gray matter volume in the right paracingulate sulcus, the left occipito-temporal cortex, and the left inferior frontal sulcus. On the contrary, the gray matter volume in the bilateral cerebellum was increased. Otherwise, they showed increased volume in the left amygdala/periamygdaloid cortex, the right inferior temporal gyrus, and the middle temporal gyrus.

Recently, the development of functional neuroimaging also provided some evidence for the correlation between amygdala deficit and ASD. A study using Technetium-99m (Tc-99m) single-photon emission computed tomography (SPECT) found that regional cerebral blood flow (rCBF) was decreased in the bilateral insula, superior temporal gyri, and left prefrontal cortices in individuals with ASD compared to age- and gender-matched controls with mental retardation [ 79 ]. Also, the authors found that rCBF in both the right hippocampus and amygdala was correlated with a behavioral rating subscale.

On proton magnetic resonance spectroscopy (MRS) in the right hippocampal-amygdala region and the left cerebellar hemisphere, autistic subjects showed decreased level of N-acetyl aspartate (NAA) in both areas [ 80 ]. There was no difference in the level of the other metabolites, such as creatine and choline. This study implies that a decreased level of NAA might be associated with neuronal hypofunction or immature neurons.

These findings support the claim that amygdala might be a key structure in the development of ASD and a target for the management of the disease.

Prefrontal cortex and ASD

Frontal lobe has been considered as playing an important role in higher-level control and a key structure associated with autism. Individuals with frontal lobe deficit demonstrate higher-order cognitive, language, social, and emotion dysfunction, which is deficient in autism [ 81 ]. Recently, neuroimaging and neuropsychological studies have attempted to delineate distinct regions of prefrontal cortex supporting different aspects of executive function. Some authors have reported that the excessive rates of brain growth in infants with ASD, which is mainly contributed by the increase of frontal cortex volume [ 82 , 83 ]. Especially, the PFC including Brodmann areas 8, 9, 10, 11, 44, 45, 46, and 47 has been noted for the structure related with ASD [ 84 ]. The PFC is cytoarchitectonically defined as the presence of a cortical granular layer IV [ 85 ], and anatomically refers to the regions of the cerebral cortex that are anterior to premotor cortex and the supplementary motor area [ 86 ]. The PFC has extensive connections with other cortical, subcortical and brain stem sites [ 87 ]. It receives inputs from the brainstem arousal systems, and its function is particularly dependent on its neurochemical environment [ 88 ].

The PFC is broadly divided into the medial PFC (mPFC) and the lateral PFC (lPFC). The mPFC is further divided into four distinct regions: medial precentral cortex, anterior cingulate cortex, prelimbic and infralimbic prefrontal cortex [ 89 ]. While the lPFC is thought to support cognitive control process [ 90 ], the mPFC has reciprocal connections with brain regions involved in emotional processing (amygdala), memory (hippocampus) and higher-order sensory regions (within temporal cortex) [ 91 ]. This involvement of mPFC in social cognition and interaction implies that mPFC might be a key region in understanding self and others [ 92 ].

The mPFC involves in fear learning and extinction by reciprocal synaptic connections with the basolateral amygdala [ 93 , 94 ]. It is believed that the mPFC regulates and controls amygdala output and the accompanying behavioral phenomena [ 95 , 96 ]. Previous authors investigated how memory processing is regulated by interactions between BLA and mPFC by means of functional disconnection [ 97 , 98 ]. Disturbed communication within amygdala-mPFC circuitry caused deficits in memory processing. These informations provide support for a role of the mPFC in the development of ASD.

Nucleus Accumbens and ASD

Besides amygdala, nucleus accumbens (NAc) is also considered as the key structure which is related with the social reward response in ASD. NAc borders ventrally on the anterior limb of the internal capsule, and the lateral subventricular fundus of the NAc is permeated in rostral sections by internal capsule fiber bundles. The rationale for NAc to be considered as the potential target of DBS for ASD is its predominant role in modulating the processing of reward and pleasure [ 99 ]. Anticipation of rewarding stimuli recruits the NAc as well as other limbic structures, and the experience of pleasure activates the NAc as well as the caudate, putamen, amygdala, and VMPFC [ 100 , 101 , 102 ]. It is well known that dysfunction of NAc regarding rewarding stimuli in subjects with depression. Bewernick et al. demonstrated antidepressant effects of NAc-DBS in 5 of the 10 patients suffering from severe treatment-resistant depression [ 103 ].

Two groups reported about the neural basis of social reward processing in ASD. Schmitz et al. examined responses to a task that involved monetary reward. They investigated the neural substrates of reward feedback in the context of a sustained attention task, and found increased activation in the left anterior cingulate gyrus and left mid-frontal gyrus on rewarded trials in ASD [ 104 ]. Scott-Van Zeeland et al. investigated the neural correlates of rewarded implicit learning in children with ASD using both social and monetary rewards. They found diminished ventral striatal response during social, but not monetary, rewarded learning [ 105 ]. According to them, activity within the ventral striatum predicted social reciprocity within the control group, but not within the ASD group.

Anticipation of pleasurable stimuli recruits the NAc, whereas the experience of pleasure activates VMPFC [ 106 ]. NAc is activated by incentive motivation to reach salient goals [ 106 ]. Increased activation in the left anterior cingulate gyrus and left mid-frontal gyrus was noted during both the anticipatory and consummatory phase of the reward response [ 104 , 107 , 108 ]. However, the activity within the ventral striatum was decreased in autistic subjects, which caused impairment in social reciprocity [ 105 ].

These findings indicate that reward network function in ASD is contingent on both the temporal phase of the response and the type of reward processed, suggesting that it is critical to assess the temporal chronometry of responses in a study of reward processing in ASD. NAc might be one of the candidates as a target of DBS which is introduced as below.

Various educational and behavioral treatments have been the mainstay of the management of ASD. Most experts agree that the treatment for ASD should be individualized. Treatment of disabling symptoms such as aggression, agitation, hyperactivity, inattention, irritability, repetitive and self-injurious behavior may allow educational and behavioral interventions to proceed more effectively [ 109 ].

Increasing interest is being shown in the role of various pharmacological treatments. Medical management includes typical antipsychotics, atypical antipsychotics, antidepressants, selective serotonin reuptake inhibitors, α2-adrenergic agonists, β-adrenergic antagonist, mood stabilizers, and anticonvulsants [ 110 , 111 ]. So far, there has been no agent which has been proved effective in social communication [ 112 ]. A major factor in the choice of pharmacologic treatment is awareness of specific individual physical, behavioral or psychiatric conditions comorbid with ASD, such as obsessive-compulsive disorder, schizophrenia, mood disorder, and intellectual disability [ 113 ]. Antidepressants were the most commonly used agents followed by stimulants and antipsychotics. The high prevalence of comorbidities is reflected in the rates of psychotropic medication use in people with ASD. Antipsychotics were effective in treating the repetitive behaviors in children with ASD; however, there was not sufficient evidence on the efficacy and safety in adolescents and adults [ 114 ]. There are also alternative options including opiate antagonist, immunotherapy, hormonal agents, megavitamins and other dietary supplements [ 109 , 113 ].

However, the autistic symptoms remain refractory to medication therapy in some patients [ 115 ]. These individuals have severely progressed disease and multiple comorbidities causing decreased quality of life [ 44 , 110 ]. Interventional therapy such as deep brain stimulation (DBS) may be an alternative therapeutic option for these patients.

Two kinds of interventions have been used for treating ASD; focused intervention practices and comprehensive treatments [ 116 ]. The focused intervention practices include prompting, reinforcement, discrete trial teaching, social stories, or peer-mediated interventions. These are designed to produce specific behavioral or developmental outcomes for individual children with ASD, and used for a limited time period with the intent of demonstrating a change in the targeted behaviors. The comprehensive treatment models are a set of practices performed over an extended period of time and are intense in their application, and usually have multiple components [ 116 ].

Since it was approved by the FDA in 1997, DBS has been used to send electrical impulses to specific parts of the brain [ 117 , 118 ]. In recent years, the spectrum for which therapeutic benefit is provided by DBS has widely been expanded from movement disorders such as Parkinson's disease, essential tremor, and dystonia to psychiatric disorders. Some authors have demonstrated the efficacy of DBS for psychiatric disorders including refractory obsessive-compulsive disorder, depression, Tourette syndrome, and others for the past few years [ 119 , 120 , 121 ].

To the best of our knowledge, there have been 2 published articles of 3 patients who underwent DBS for ASD accompanied by life-threatening self-injurious behaviors not alleviated by antipsychotic medication [ 122 , 123 ]. The targets were anterior limb of the internal capsule and globus pallidus internus, only globus pallidus, and BL nucleus of the amygdala, respectively. All patients obtained some benefit from DBS. Although the first patient showed gradual re-deterioration after temporary improvement, the patient who underwent DBS of the BL nucleus experienced substantial improvement in self-injurious behavior and social communication. These experiences suggested the possibility of DBS for the treatment of ASD. For patients who did not obtain benefit from other treatments, DBS may be a viable therapeutic option. Understanding the structures which contribute to the occurrence of ASD might open a new horizon for management of ASD, particularly DBS. Accompanying development of neuroimaging technique enables more accurate targeting and heightens the efficacy of DBS. However, the optimal DBS target and stimulation parameters are still unknown, and prospective controlled trials of DBS for various possible targets are required to determine optimal target and stimulation parameters for the safety and efficacy of DBS.

ASD should be considered as a complex disorder. It has many etiologies involving genetic and environmental factors, and further evidence for the role of amygdala and NA in the pathophysiology of ASD has been obtained from numerous studies. However, the key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.

Acknowledgements

This study was partly supported by the Korea Institute of Planning & Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries, Republic of Korea (311011-05-3-SB020), by the Korea Healthcare Technology R&D Project (HI11C21100200) funded by Ministry of Health & Welfare, Republic of Korea, by the Technology Innovation Program (10050154, Business Model Development for Personalized Medicine Based on Integrated Genome and Clinical Information) funded by the Ministry of Trade, Industry & Energy (MI, Korea), and by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3C7A1028926).

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• Published: 16 January 2020

Autism spectrum disorder

• Catherine Lord 1 ,
• Traolach S. Brugha 2 ,
• Tony Charman 3 ,
• James Cusack 4 ,
• Guillaume Dumas 5 ,
• Thomas Frazier 6 ,
• Emily J. H. Jones 7 ,
• Rebecca M. Jones 8 , 9 ,
• Andrew Pickles 3 ,
• Matthew W. State 10 ,
• Julie Lounds Taylor 11 &
• Jeremy Veenstra-VanderWeele 12  

Nature Reviews Disease Primers volume  6 , Article number:  5 ( 2020 ) Cite this article

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• Autism spectrum disorders
• Cognitive neuroscience
• Paediatrics

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

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Acknowledgements

The authors thank J. McCauley, S. Gaspar, K. Byrne and A. Holbrook from UCLA for help with manuscript preparation. S. Tromans is thanked for his updated review of the epidemiology literature. We recognize the many investigators who contributed research that we cannot cite due to space limitations. C.L. is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHHD; R01 HD081199), the National Institute of Mental Health (NIMH; R01MH081873-01A1) and the Simons Foundation. T.S.B. is supported by grants from the Health and Social Care Information Centre, Leeds, and the National Institute for Health Research (NIHR HTA; grant ref. NIHR127337). T.C. is supported by grants from Innovative Medicines Initiative 2 (no. 777394), the Medical Research Council (MRC; grants MR/K021389/1) and the NIHR (grant 13/119/18). J.C. is funded by Autistica. G.D. is supported by the Institut Pasteur. T.F. is supported by the Autism Speaks Foundation. E.J.H.J. is supported by grants from the Economic and Social Research Council (ESRC; ES/R009368/1), the Innovative Medicines Initiative 2 (no. 777394), the MRC (MR/K021389/1) and the Simons Foundation (609081). R.M.J. acknowledges the Mortimer D. Sackler Family and the NIMH (R01MH114999). J.L.T. is supported by grants from the FAR fund and the NIMH (R34 MH104428, R03 MH 112783 and R01 MH116058). A.P. is partially supported by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR (NF-SI-0617-10120). M.W.S. is supported by the National Institutes of Health (NIH; MH106934, MH109901, MH110928, MH116487 MH102342, MH111662, MH105575 and MH115747), the Overlook International Foundation and the Simons Foundation. J.V.-V. is supported by the NIH (MH016434 and MH094604), the Simons Foundation and the New York State Psychiatric Institute. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.

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All authors read and edited the full document. Introduction (C.L.), Epidemiology (T.S.B.), Mechanisms/pathophysiology (M.W.S., G.D., R.M.J., T.C. and E.J.H.J.), Diagnosis, screening and prevention (T.C., E.J.H.J. and T.S.B.), Management (T.S.B., T.C., E.J.H.J., J.L.T. and J.V.-V.), Quality of life (J.L.T., J.C. and T.F.), Outlook (C.L. and A.P.), Overview of Primer (C.L.).

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C.L. acknowledges the receipt of royalties from Western Psychological Services for the sale of the Autism Diagnostic Interview-Revised (ADIR), the Autism Diagnostic Observation Schedule (ADOS) and the Social Communication Questionnaire (SCQ). T.S.B. has received royalties from Cambridge University Press and Oxford University Press. T.C. has served as a consultant to F. Hoffmann-La Roche. and has received royalties from Guilford Publications and Sage Publications. T.F. has received federal funding research support from, acted as a consultant to, received travel support from, and/or received a speaker’s honorarium from the Brain and Behaviour Research Foundation, Bristol-Myers Squibb, the Cole Family Research Fund, EcoEos, Forest Laboratories, Ingalls Foundation, IntegraGen, Kugona LLC, the National Institutes of Health, Roche Pharma, Shire Development and the Simons Foundation. J.L.T. receives compensation from Sage Publishers for editorial work. A.P. receives royalties from Imperial College Press, Oxford University Press and Western Psychological Services. M.W.S. serves on the scientific advisory boards and has stock or stock options for Arett Pharmaceuticals and BlackThorn Therapeutics. J.V.-V. has consulted or served on an advisory board for Novartis, Roche Pharmaceuticals and SynapDx, has received research funding from Forest, Novartis, Roche Pharmaceuticals, Seaside Therapeutics, SynapDx, and has received an editorial stipend from Springer and Wiley. All other authors declare no competing interests.

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Lord, C., Brugha, T.S., Charman, T. et al. Autism spectrum disorder. Nat Rev Dis Primers 6 , 5 (2020). https://doi.org/10.1038/s41572-019-0138-4

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Suicide rate higher for people with autism

University of Queensland-led research has found people on the autism spectrum are almost 3 times more likely to die by suicide compared to non-autistic people.

Dr Damian Santomauro from UQ’s School of Public Health and the Queensland Centre for Mental Health Research led a team which conducted a systematic review of nearly 1500 international research papers. 

“We aimed to quantify the risk, mortality and burden of suicide among people on the autism spectrum,” Dr Santomauro said. 

“There were several alarming findings in this study, including the fact people on the autism spectrum but without intellectual disability were more than 5 times more likely to die by suicide compared to people not on the autism spectrum.

"In 2021, the total years of life lost to the increased risk of suicide in the autistic community exceeded those lost to cocaine use, rabies or testicular cancer across the total global population. 

“And almost 2 per cent of all suicide deaths globally in 2021 could have been avoided if the risk for death by suicide for autistic people was not elevated.”

Dr Santomauro said there were likely many reasons for the higher associated risk.

“People on the autism spectrum often experience bullying, social rejection, stigma and discrimination – all risk factors for depressive disorders,” he said.

“There can also be other challenges for autistic people that impact their educational progress, employment, independent living and peer relationships.”

Dr Santomauro said the findings showed a critical need for interventions and prevention strategies.

“Measures to reduce risk factors for suicide among autistic people would substantially reduce the fatal burden of suicides globally and the health burden experienced by people on the autism spectrum,” he said.

“Studies like this one are important, to get an idea of how issues impact people on the autism spectrum.  

“Without these estimates there would be no gauge for policy makers or service providers on the mortality and burden of suicide for autistic people.”

The study also involved researchers from Deakin University, La Trobe University, the University of Leicester, the Institute for Health Metrics and Evaluation and the University of Washington.

The study was published in Psychiatry Research .

If you or anyone you know needs support, please contact:

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