What is Autism Spectrum Disorder (ASD)?

Child playing

Autism Spectrum Disorder is a pervasive early developmental disorder that strongly impacts how an individual socially engages with his/her world. The affected individual may display poor eye contact, blunted reaction to emotional events and/or difficulty understanding the intentions of others, although there is a range in social ability within ASD. Language development is also usually impacted at early ages, with failures to develop typical speech and language understanding as among the most common first signs of the disorder. Toddlers with autism are often “late talkers” and a small percentage, less than 5%, remain non-verbal throughout their lives. Fortunately, most children with ASD do gain the ability to converse. Another important feature of the disorder is having unusually narrow interests and/or engagement in repetitive behavior. These behaviors pose further challenges to social interactions for the individual with ASD and the people in his or her world.

In the distant past, the prevalence was estimated at 1 in every 2,000 children. Today, one out of every 68 children is affected with autism or a related disorder 1. Thus, it is more prevalent than breast cancer or childhood diabetes. The recurrence rate for having a second child with autism in families that already have a child with ASD, is 15-20%2.

In 2013, the American Psychiatric Association released the newest version of the Diagnostic and Statistical Manual of Mental Disorders (the DSM-5). In this edition, previous subtypes of Autism Spectrum Disorder including Autistic Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, Asperger Syndrome, and Child Disintegrative Disorder, were included together under the single diagnosis of Autism Spectrum Disorder or “ASD.”

Twenty years ago the mean age of diagnosis nationally was around age 5 years. Today, many children in major urban areas with Universities active in ASD research, are being diagnosed near their third birthday. In San Diego, Dr. Karen Pierce at the University of California Autism Center of Excellence has transformed early risk detection and diagnostic follow-up. Because of her effort, autism risk and early diagnosis commonly occurs here by ages 12 months to 24 months. These are dramatic changes due to use of Dr. Pierce’s Get SET Early approach to early identification in conjunction with over 100 participating pediatricians in San Diego County.

A “gold standard” in ASD diagnostic assessments is the Autism Diagnostic Observation Schedule or ADOS that was created by Catherine Lord, Ph.D. and colleagues.

Currently a new diagnostic module, called the “ADOS, Toddler Module,” is available for use with infants as young as 12-months old to help the UCSD Autism Center of Excellence clinicians to establish a diagnostic risk profile. The implementation of general screening approaches, such as Dr. Karen Pierce’s Get SET Early Model, which trains pediatricians to start screening for ASD starting at the 1 Year Well-Baby Check-Up as well as at visit thereafter, has lead to dramatically earlier detection, evaluation and treatment.

Other early diagnosis efforts are being researched at the UCSD Autism Center as well as around the country including efforts to develop a diagnostic test for autism based on patterns of functional brain activity, eye tracking, or genetic profile. Each of these pioneering areas of research are currently ongoing at the UCSD Autism Center of Excellence (ACE).

Biological Factors

A significant percentage of infants and toddlers with ASD have early brain overgrowth. This was originally discovered in 2001 at the UCSD Autism Center of Excellence by Dr. Eric Courchsne, Director. Early brain overgrowth may underlie specific neurofunctional and clinical phenotypic subtypes in ASD in the first years of life. The cause of it is found in prenatal life when an abnormal overabundance of brain cells are produced in the 1st and 2nd trimesters. Dr. Courchesne also discovered this and in 2011 in JAMA reported that ASD children have an average of 67% too many neurons in frontal cortex, a region important for higher-order cognitive, language, social and emotional functions. Dr. Courchesne and his colleagues at UCSD also discovered excess neuron proliferation (production) but reduced synapse formation in cell models of living ASD toddlers with early brain overgrowth in 2016 in Molecular Psychiatry. Dr. Pramparo also at the UCSD Autism Center recently discovered dysregulation of cell cycle hub genes in ASD toddlers with brain overgrowth in 2016 (REF). Cell cycle hub genes regulate the number and type of brain cells produced in the prenatal brain and so this discovery also points to 1st and 2nd excess neuron proliferation as leading to early brain overgrowth and autism behaviors.

A great deal of new research also shows that a significant percentage of high confidence ASD gene mutations dysregulate prenatal neuron proliferation. Animal models of ASD also show that when there is an excess of cortical neurons in prenatal life, the mouse offspring display brain overgrowth, ASD-like behaviors and excitatory brain connectivity patterns consistent with ASD literature and theory. A new analyses of all existent brain imaging studies of ASD (about 44 such studies) conclusively confirms that ASD involves significant brain enlargement, especially at young ages.

Dr. Courchesne and his colleagues also find that after a period of early brain overgrowth, there is a phase of slowed growth; there may eventually be decline in some subset of individuals. Key brain regions thought to contribute to the symptomology of autism include the:

  • Amygdala, which is involved in emotion regulation
  • Superior temporal gyrus, which is involved in the development of complex language processing ability
  • Frontal lobes, which are involved in higher order cognition and communication including the ability to engage in sophisticated social behavior and understanding another person’s feelings and social perspective

Causes of Autism

The likely causes of autism are being uncovered. Major advances have occurred in discovering a large number of genes which when mutated may contribute to or directly cause ASD. About 50 such genes are so called “high confidence” genes and very likely play key roles. However, such gene mutations onl;y occur in a very tiny percentage of cases. For instance, CHD8 gene mutations occur in about 4 ASD individuals out of 1000 ASD individuals; this rare cause is the single most common gene cause; all others are even rarer. A substantial 30 to 45% of autism risk comes from common genetic variation and not mutation. Another 30 to 45% risk appears to be environmental. Exactly which common gene variations are critical remain largely unknown.

Much evidence points to important environmental factors, such as exposure to viruses or toxins during the 1st or early 2nd trimesters of pregnancy. There are a large number of ASD animal and cellular model studies and epidemiology studies examining the possible role of maternal immune activation or MIA and autism.

One surprising discovery by Dr. Courchesne and his graduate student, Dr. John Morgan, is that one type of cell in the brain called microglia are strikingly abnormal or “activated”. Activated microglia is a clear indicator of on-going neuroinflammatory processes in the ASD brain, even at ages as young as 2 years. This immune signal has been found now is a great many types of studies and appears to be one of the most common pathological features present in the ASD brain.

The UCSD Autism Center of Excellence has found a highly accurate signature of ASD in at risk 1 and 2 year olds; this was reported in Pramparo et al. in JAMA Psychiatry 2015. Importantly the key feastures of this ASD signature include dysregulation of immune genes and cell cycle genes, as well as genes that regulate translation.

The symptoms of ASD can vary widely. For example, some children may demonstrate extremely poor eye contact, whereas other children with an ASD may demonstrate good eye contact. Some children may not talk at all, whereas other children with ASD may have very good productive language and even be able to converse with others. The dissimilarity of ASD symptoms probably reflects the complexity of brain abnormalities and the underlying genetics that likely involve multiple genes and gene-environment interactions.

Clinical Symptoms

Deficits in Social Communication and Social Interaction

Individuals with ASD show persistent deficits in social and communicative skills which may be apparent in their social-emotional reciprocity, nonverbal communication, and developing and maintaining relationships with others.

Children with ASD often have difficultly initiating and maintaining interaction with others. This may be seen as reduced showing of objects, babbling or other communication to others, or sharing of emotions or affect. A child with ASD may also have difficulty responding to others, which may manifest as failure to respond to their name, difficulty participating in social games, or an overall reduced interest in people.

Deficits in nonverbal communication include difficulty integrating verbal and nonverbal communicative behaviors, such as coordinating eye contact with vocalizations, reduced use of gestures, and lack of facial expressions.

Children with ASD also show difficulties with relationships with others, including a lack of interest in other children or difficulties in play. For example, a child with ASD may prefer to play alone rather than joining a group of children. They also commonly have difficulties with imitating or engaging in pretend and imaginative play where you interact or pretend with objects, such as feeding a baby doll or pretending to talk on a phone.

Restricted and Repetitive Patterns of Behavior

Individuals with ASD also display restricted, repetitive and stereotyped patterns of interests and activities. This general category of behavior manifests itself in many ways such as an inflexible adherence to specific routines, stereotyped and repetitive behaviors, preoccupations with unusual objects, or unusual reactions to sensory input.

In general, individuals with ASD display a significantly reduced interest in their environment, instead, focusing their attention on one specific aspect of the environment (e.g., a lamp) or obsessive idea (e.g., amassing facts about cars). Further, individuals with ASD may display rigid behaviors and insist on sameness with distress over trivial changes in their environment (e.g., movement of a piece of furniture).

Children with ASD may also engage in repetitive behaviors such as repetitive motor movements (e.g. hand flapping), repetitive use of objects (e.g. lining of toys), or repetitive use of speech (e.g. repeating sounds, words, or phrases). They may also have unusual responses to different sensory information, such as a fascination with lights or spinning objects, oversensitivity to loud noises, or adverse responses to certain textures.

Restricted and repetitive environmental interests likely interfere with learning and may have significant developmental implications for the autistic child because he or she may miss many learning opportunities that fall outside their scope of interest. Combined with attention deficits described above, the autistic child often has difficulty learning from his or her environment.

Available Treatments

A wide range of therapies exist to treat the symptoms of autism, most of which are based on a behavioral and/or a developmental model. Commonly used treatments under the Applied Behavior Analysis (ABA) model (?) include:

Therapies based on a “behavioral” model rely on the principles of behavior and attempt to teach child skills by providing specific cues and consequences for behavior in order to teach the child new skills. Therapies based on a “developmental” model focus on identifying a child’s current ability level and guiding him or her through a sequence of learning experiences that become more developmentally complex across time.

While most therapies combine insight from both behavioral and developmental models, some therapies are heavily weighted towards either approach. For example, DTT relies heavily on the principles of behavior whereas FT relies heavily on principles of development.

Aside from isolated medications that may be beneficial at targeting specific symptoms such as seizures, there is no medicine or pill to treat autism. Alternative therapies exist such as hyperbaric oxygen or chelation therapy, but there is no scientific evidence to suggest that these therapies are effective. Such alternative therapies also come with some level of safety risk.

1. Christensen D. L., Baio J., Van Naarden Braun K., Bilder D., Charles J., Constantino J. N., et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016 Apr 1;65(3):1-23. [PMCID].

2. Ozonoff S., Young G. S., Carter A., Messinger D., Yirmiya N., Zwaigenbaum L., et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics. 2011 Sep;128(3):e488-495. [PMCID: PMC3164092].