Autism Spectrum Disorder (ASD)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can affect the way in which people interact, communicate, behave and learn. Although it is a spectrum disorder with a wide variation in the behaviors displayed and severity of symptoms, core symptoms include persistent deficits in social communication and social interaction across multiple contexts and restricted/repetitive patterns of behavior, interests or activities. In 2013, ASD terminology was changed from the 3 different subgroups (Autistic Disorder, Asperger’s disorder and pervasive developmental disorder not otherwise specified) to a single entity, ASD. This was changed after a study reported that there was a lack of reliability in clinical distinction among the 3 different diagnostic subtypes.
The prevalence of ASD has increased 400% since 2004. The diagnostic rates of individuals diagnosed with both ASD and intellectual disability (ID) have not changed. What has increased significantly is the diagnosis of children with ASD without intellectual impairment. Often these children are not diagnosed until the environment requires the use of higher-level social skills. Approximately 25% of individuals with ASD are diagnosed at age 9 years or older. Although ASD lasts throughout the lifespan, core symptoms can improve over time, especially with treatment.
Role of the Primary Care Provider (PCP)
It is important to highlight the critical role of PCPs in screening, early detection, referrals and early intervention in identification and treatment of youth with ASD. This module is not specifically focused on diagnosis or treatment of ASD but on identification and treatment of co-occurring mental health diagnoses in youth with ASD, as these are extremely common.
Attention deficit/Hyperactivity disorder, depression, anxiety, irritability, oppositional defiant disorder, suicidal ideation and psychosis are all more common in individuals with ASD than the general population. Primary care providers are often the first to detect and respond to these concerns and play a crucial role in early detection, timely intervention and coordination of appropriate care. Youth with more severe symptoms may require referrals to behavioral health providers, such as specialized therapists or psychiatrists. However, it is important that all caregiver teams include the PCP as they are crucial in offering longitudinal, whole-person care needed for these youth.
MYTH: Vaccines cause ASD.
Fact: There is no evidence to support any link between vaccinations or their preservatives and ASD.
MYTH: ASD can be cured with medications
Fact: ASD cannot be cured with medications. Medications and behavioral treatment can help improve some of the core symptoms of ASD and improve the level of functioning of the individual. However, they cannot cure ASD.
MYTH: Cannabis is an effective medication to treat core symptoms of ASD.
Fact: The American Academy of Child and Adolescent Psychiatry (AACAP) has reported risk of harm for children and adolescents using marijuana and cannabinoids. Consistent use of marijuana at a young age can cause lasting deficiencies in cognition, changes in brain structure and a possible decline in IQ. Use in adolescence has been associated with increased rates and worsening of psychotic, mood and anxiety disorders. AACAP’s recommendations are against the use of medical marijuana or isolated cannabinoids to treat core symptoms of ASD or co-occurring mental health diagnoses.
ASD is defined by persistent deficits in social communication and interactions in multiple environments and circumstances. There are often deficits in the ability to engage in back-and-forth conversation and a reduced sharing of interests. There are deficits in nonverbal communication, such as eye contact, body language or in using or understanding gestures. Individuals with ASD often have difficulty in initiating and maintaining relationships. These individuals exhibit restricted repetitive interests, behaviors (RRBs) or activities. This can take the form of repetitive movements or speech, insistence on sameness and/or routines, preoccupation with specific items or topics or sensory concerns. With more pronounced symptoms, youth can be identified at an early age. However, at times, the full range of symptoms will not be seen until school age or later when more highly developed social skills are needed (e.g. being able to interpret body language, maintaining back-and-forth conversation or initiating/maintaining friendships), resulting in a later diagnosis.
Often when discussing ASD, there is reference to “interfering symptoms”. These are typically considered to be irritability, inattention/hyperactivity, social deficits and repetitive behaviors. A high percentage of individuals with ASD exhibit one or all of these symptoms. Irritability and inattention/hyperactivity are frequently treated with psychotropic medications. Social deficits are often treated with behavioral interventions such as applied behavior analysis or social skill group participation depending on the age and/or level of functioning.
Clinical Pearl: ASD and OCD
It can be difficult to discern the difference between RRBs (as described above) and interest as a part of ASD and the obsession and compulsions due to a co-morbid diagnosis of obsessive-compulsive disorder (OCD). There are several factors that can help to differentiate between the two. First, the restricted, repetitive behaviors and interests that are a core feature of ASD do not cause distress to the individual. In fact, they are often used to help them calm and are often enjoyable to the individual. Obsessions and compulsions in individuals with OCD typically cause them distress and interfere with the individual’s functioning. The RRBs performed in ASD are typically seen at their baseline and do not typically worsen over time. OCD symptoms are usually a change from baseline and can wax and wane in intensity.
Samuel is a 6y/o male who was diagnosed with ASD when he was 3 years of age. He met all speech milestones and has normal IQ. He makes poor eye contact and misreads social cues. He started kindergarten 3 months ago. His mother brought him to the pediatrician’s office as he has been in frequent trouble at school for hitting other kids, refusing to follow instructions, and not complying with group activities. At home, Mother has noted that Samuel has always been “a very hyper child” but is more defiant and agitated lately. Mother reports that yesterday she asked him to put away a toy and he threw it down and broke it. Mother reports that he has always been somewhat irritable, but it has escalated over the past 2 months, with the irritability much worse over the past month. Mother reports that he is always on edge causing the family “to walk on egg shells”. He refuses to answer any of the pediatrician’s questions.
Sara is a 13 y/o female diagnosed with ASD at 9 years of age. She exhibited some difficulties with making and maintaining friendships in her first few years of school. She excelled in her school work and had normal eye contact, so ASD was not initially considered. As she became older, her cognitive rigidity (inability to see others’ point of view, insistence on routine and doing things in a certain way) became more impairing and her inability to read facial cues and body language became more apparent. Her mother brings her to the pediatrician’s office today due to her recent increase in irritability. Mother reports that she is unsure if it is “just her hormones” or if she has “a chemical imbalance”. Mother reports that the patient has always needed things to be “just right” and “her way” but this has been escalating for the past several months. She has also noted that Sara seems to be having trouble sleeping and more trouble than normal, getting along with others. When the pediatrician attempts to ask Sara questions regarding the changes in behavior, she appears annoyed and agitated.
Common Co-morbidities in individuals with ASD
Sleep problems are very common in individuals with ASD. It is estimated that between 50-80% of youths with ASD have sleep difficulties. Chronic sleep deprivation has been linked to poor attention, moodiness, anxiety, depression, hyperactivity and aggression in individuals with ASD. Sleep issues in those with ASD are most likely to be multi-factorial in nature with biological, medical (sleep apnea) and/or behavioral components.
There are several biological factors that likely contribute to poor sleep in youths with ASD; these include arousal dysregulation, amygdala activation and irregularities in the melatonin pathway. It is thought that there is an arousal dysregulation in individuals with ASD that ties together anxiety, insomnia and sensory sensitivities that leads to youths feeling that they “can’t turn their brain off” at night. This leads to insomnia at night and over-arousal during the day. This phenomenon is thought to be caused by a dysregulation in the HPA axis with cortisol levels not falling at night, a phenomenon more common in youths with ASD. In addition, some individuals with ASD experience an increase in amygdala activation with sleep deprivation, which is thought to predispose them to an increase in agitation/aggression. There is also a theorized abnormality in the processing of melatonin, which can contribute to difficulty sleeping.
Treatment of sleep in ASD is divided into behavioral and pharmacologic interventions. The behavioral sleep interventions are further divided into daytime habits, evening habits and sleep environment. During the day it is important to try to promote exercise and light exposure. When individuals stay in dark rooms, melatonin is released. This can be a factor in promoting daytime sleepiness and insomnia. It is also important to limit caffeine use and napping and have selective use of the bedroom (i.e.do not use for behavioral time outs). Evening habits include limiting stressful or stimulating activity in the evening and establishing a bedtime routine. It can be helpful in youth with ASD to create a bedtime checklist with pictures they can check off after they complete each item.
Pharmacologic options have been understudied and are not Food and Drug Administration (FDA) approved for the treatment of insomnia in youth with ASD. Behavioral interventions should always be trialed prior to initiating medications. Melatonin is the most studied and best tolerated pharmacological intervention in youth with ASD-related insomnia. The half-life of immediate release melatonin is one hour, which can lead to nighttime awakenings. Using extended release melatonin may help mitigate this.
Irritability is frequently noted in individuals with ASD. When treating irritability in those with ASD, it is important to consider level of functioning prior to reports of irritability beginning. Next, it is important to consider/address all possible contributors to the irritability: medical conditions, sleep issues, psychosocial stressors, problems with communication, maladaptive reinforcement patterns and co-occurring mental health disorders. Medical conditions such as tooth caries, ear infections, food allergies, constipation and GERD are frequent in this population and can cause pain that can trigger irritability. It is important to consider any psychosocial stressors as well. Changes in home or school environment can be difficult for youths with ASD and cause irritability. Youths with ASD are more likely to be victims of traumatic events than their peers without developmental disabilities. There are many co-morbid mental health disorders that can increase/cause irritability. It is important to screen for depression, anxiety and attention deficit hyperactivity disorder (ADHD) and treat these first if they are present.
Risperidone and aripiprazole are approved by the FDA to treat irritability associated with ASD in individuals 5-16 years of age. These medications can cause significant weight gain and movement disorders among other side effects. Thus, it is important to consider and address all other possible contributors to irritability and co-occurring mental health co-morbidities prior to initiating these medications.
Clinical Pearl: Depression, Anxiety, and ADHD
Depression, anxiety, and ADHD are all co-morbid conditions that can cause or increase irritability in youth with ASD. If these disorders are present, it is important to treat these first, because risperidone and aripiprazole are likely to be ineffective to treat these comorbid conditions and can increase the risk of adverse effects. Treating these disorders will often relieve the irritability.
Attention Deficit Hyperactivity Disorder (ADHD)
ADHD is the most common co-morbid diagnosis in youths with ASD. Hyperactivity, impulsivity and inattention are frequently noted in youths with ASD. Parent and teacher Vanderbilt screening tools are often used to screen children who exhibit symptoms consistent with ADHD.
Treatment for ADHD has been reported to improve symptoms of hyperactivity, inattention, impulsivity, irritability and defiance in youths with ASD and ADHD. Studies of youths with ASD treated with a stimulant, have reported higher incidence of side effects and significantly lower response rates than in their peers. Due to this, the mantra of “start low and go slow” is used when prescribing stimulants to youths with ASD.
The pediatrician performs a review of systems and physical exam to rule out possible medical conditions. The pediatrician asks about recent environmental or schedule changes. Mother states the patient started kindergarten 3 months ago. She states he is “in trouble a lot” at school. The pediatrician screens for depression, anxiety and ADHD. He screens positive on the Vanderbilt for ADHD. The pediatrician refers the patient to an outpatient therapist to help mother and patient adjust to the change of starting school. The pediatrician starts low-dose methylphenidate for ADHD.
Suicidal Thinking and Behaviors
Suicidal thinking and behaviors are common in individuals with ASD. It is important to screen for suicidal thinking in this population. There are no validated tools currently available for assessing suicide risk in youth with ASD; however, the Ask Suicide-Screening Questions (ASQ) has been used in studies.
Recent studies have reported that individuals with ASD are more likely to die by suicide than those without ASD. Rates of suicide attempts and deaths by suicide are 3 times higher in those with ASD. Attempts in this population are seen about 3.6 years earlier than in those individuals without ASD. Suicide attempts in this population are often more lethal and aggressive as individuals with ASD often struggle with low frustration tolerance and cognitive rigidity. They may become very upset with their own mistakes or failures. They may also exhibit significant distress when others do not follow rules. These rules can include basic environmental or context specific rules. In addition, these youths are often bullied at school due their deficits in social skills or what others perceive as odd behaviors. These factors with the addition of a high level of impulsivity can lead to more lethal and aggressive suicide attempts than those reported in youths without a developmental disability. Risk factors for suicide attempts in those with ASD include anxiety, uncomfortable sensory experiences, low frustration tolerance, impulsivity, difficulties with changes in routine or schedule. The largest risk factor for suicide attempts in this population is mental health co-morbidities.
Individuals with ASD have high rates of depressive disorders. Studies have reported depressive disorders in as many as half of individuals with ASD. Onset of depression in youths with ASD averages 10 years of age, which is earlier than in youth without a developmental disability. Contributing factors for depressive disorders include trauma, higher IQ and camouflaging.
Youths with ASD are at higher risk of trauma than youths without a developmental disability. They are at high risk of bullying due to limited social skills and understanding of social norms. These youths will frequently seek out friends on the internet. Unfortunately, they are cyberbullied at a higher rate than their peers. Youths with ASD and significant sensory issues can be at risk for trauma from blood draws or other seemingly benign events. Due to significant aggression, these individuals may be placed in seclusion or restraints due to aggressive behaviors which may be experienced as traumatic. In addition, individuals with ASD are at high risk of emotional, sexual and physical abuse.
Youths with ASD and normal IQs are at higher risk for depression than those with intellectual disabilities (ID). Individuals with ASD and normal IQs tend to understand and appreciate how they are different from their typical developing peers. They also struggle with peers making fun of them and not inviting them for activities. They often feel ostracized and alone.
Clinical Pearl: Camouflaging
Some individuals with ASD will attempt to engage in something called “camouflaging”. This term refers to adjusting behavior, speech, social interactions, likes and hobbies to “fit in” socially and attempt to hide their ASD traits. “Camouflaging” can be found in youths with ASD and without ID who present with new onset anxiety and/or depression. It is exhausting for individuals to engage in this behavior. It often leads to low self-esteem as they feel the need to “hide” their true selves. This is seen more commonly in females and those that have less impairing features of ASD. It is important to ask patients about camouflaging as it often causes them significant distress.
Self-reports of depressive mood can be difficult to assess in individuals with ASD because of language impairments and difficulty expressing and identifying emotions. Symptoms of depression in individuals with ASD can include reporting or appearing sad, changes in sleep (too much or to little), lack of interest or enjoyment in tasks that the individual has previously enjoyed, lower energy, feelings of guilt or worthlessness, difficulties with focus and suicidal ideation. Some other symptoms of depression that can be noted in youths with ASD include mood lability and/or increase in irritability/aggression. They can become more rigid in their thought process and schedules. Sometimes the theme of an individual’s special interest/preferred activity may change and become darker. For example, an individual who typically loves to read history books, may change to only reading history books about tragic events. There can be a regression in speech and adaptive function or increase in compulsive features. When assessing for depression, it is important to note symptoms occurring together and a definitive change from baseline. When evaluating a patient for depression, it is important to screen for suicidal ideation/behaviors as well.
Diagnostic overshadowing is common in this population and can lead to underdiagnosis or a misdiagnosis. Diagnostic overshadowing is the idea that symptoms are attributed to one diagnosis (ASD) and other disorders (depression, anxiety) are not explored or evaluated because it is assumed the symptoms are due to the original diagnosis (ASD). For example, an individual with ASD, the new onset of insomnia, irritability and change in theme of preferred activity to a morbid tone could all be attributed to ASD. In this case a depression diagnosis may not considered or evaluated due to diagnostic overshadowing.
Some youths with ASD present with anxiety symptoms in the same way that youths without a developmental disability do. However, self-reports of anxiety can be difficult to assess in this population due to language impairments and difficulty expressing and identifying emotions. Youths with ASD may also present anxiety differently. Sometimes youths with ASD present with anxiety symptoms that are termed “ambiguous anxiety”. Ambiguous anxiety symptoms are symptoms of anxiety that are embedded in ASD symptomatology. Youths with ASD may worry about their schedule changing or have anxiety related to preoccupation of their special interest, life transitions, or anxiety about social situations unrelated to a fear of negative evaluation by others. Some examples could include a youth that has always had difficulty with transitions or schedule changes, but now the child is constantly asking questions regarding when/if they are going to have to transition or if their schedule is changing. Schedule shifts may also cause an increase in irritability, agitation or aggression. A child may have a special interest in vacuum cleaners and now they are constantly asking questions about possible changes or lack of presence of the vacuum cleaner. Youths may start to worry about being around others or in public but the anxiety is unrelated to the worry of judgement from others. Some other symptoms of anxiety in this population can include increased rigidity, mood/behavioral dysregulation or increased irritability. It is important to assess if these symptoms represent a change from baseline status and contribute to impairment in functioning. Diagnostic overshadowing is very common when the cause of anxiety is ambiguous. It is easy to attribute ambiguous anxiety symptoms to ASD. If a youth is worried about their schedule being changed, it would be easy to think of this as a core symptom of ASD and not an anxiety symptom. Whenever there is a change in baseline behavior that is impairing it is important to consider mental health co-morbid diagnoses.
When assessing for anxiety symptoms, it is important to address any other mental health or medical conditions that could aggravate anxiety first. It also important to consider and address any psychosocial stressors that could be triggering anxiety. For example, in a youth that struggles with change, multiple changes at the same time in different environments could contribute to anxiety symptoms. It would be important to try and limit the amount of changes happening simultaneously.
Treatment of Anxiety and Depression
Modified cognitive behavioral therapy (CBT) is an effective treatment for youths with ASD and depression or anxiety without ID. CBT is used to identify and change thought and behavioral patterns that contribute to anxiety and depression. Modifications used for those with ASD include: focusing on concrete (versus abstract) material in sessions, using visual tools (feelings chart, fear thermometer) and social stories (to help with recognition of thoughts and feelings of others), and incorporating the talents and special interests of the youth into therapy sessions to keep them engaged. The involvement of parents as coaches is especially important for younger children.
In those with ID and ASD, mindfulness-based interventions as well as psychosocial and psychoeducational supports can be helpful. Mindfulness-based interventions focus on using attention to calm and not on changing thought processes like other forms of therapy. Psychosocial and psychoeducational supports include improving sleep and hygiene, increasing pleasurable activities and modifying the environment. An example of increasing pleasurable activities would be having an individual that loves animals be around them more often. Modifying an environment might be something like making a dim house brighter to help with sleep regulation.
Selective serotonin uptake inhibitors (SSRI) and selective serotonin/norepinephrine reuptake inhibitors (SNRI) can be used to treat significant anxiety and depression in youths with ASD.
Clinical Pearl: SSRIs
Youths with ASD exhibit activation as a dose dependent side effect of SSRIs at higher rates than typically developing youths. As such, using the mantra “start low and go slow” can be helpful in avoiding or limiting activation from SSRIs in youths with ASD.
Substance Use Disorders
There is some disagreement in the literature if individuals with ASD are more or less likely to have a substance use disorder than individuals without ASD. Experts have suggested that individuals with ASD tend to have a later onset of substance use disorders (SUD) but can rapidly escalate to moderate or severe disorders. Mental health co-morbidities increase the risk of SUD in individuals with ASD, specifically impulse control disorders, tic disorders and ADHD have all been reported to be risk factors for individuals with ASD developing SUD. The treatment of these co-morbid mental health conditions with psychotropic agents has been reported to decrease the risk for developing an SUD. Limited studies have been conducted on the treatment of individuals with ASD and SUD with data suggesting a role for modified CBT delivered in both individual and group therapy formats.
As the pediatrician knows of her diagnosis of ASD, she asks of any special interests or preferred topics. Mother reports that Sara loves video games. Mother has noted that over the last few months Sara is choosing video games with a more morbid theme. Mother has noted that no matter what they are doing, even if it is something historically Sara would enjoy, she seems frustrated and irritated. Sara denies changes in concentration, energy and appetite. Sara denies suicidal ideation, intent or plan. She also denies that she has been more anxious or worried. Mother denies noting that Sara has appeared anxious or worried. Due to increase in irritability, changes in theme of her special interest, change in sleep and increase in cognitive rigidity the pediatrician diagnosis her with unspecified depressive disorder. The pediatrician refers her to the local community mental health center for modified CBT.
Clinical Resources and Services
American Academy of Child and Adolescent Psychiatry Autism Spectrum Disorder Resource Center:
National Autism Association
ASD and Substance Use Disorder
Ohio Chapter of Pediatrics
Children’s Hospital of Philadelphia
Centers for Disease Control and Prevention
National Institutes of Health