Heidi C. Collins, MD

The Centers for Disease Control and Prevention estimates that autism affects 1 in every 59 children in the US.

 While the core features of autism impair functioning, a significant source of further impairment is comorbid psychiatric disorders. People with autism spectrum disorder (ASD) are more likely than the general population to have comorbid psychiatric disorders. Although prevalence rates vary widely, converging evidence suggests that anxiety disorders and ADHD are most prevalent.

Numerous factors contribute to the increased risk for comorbid psychiatric disorders. People with autism are at higher risk of being bullied and are more likely to experience adverse life events, which can increase stress and risk for depression and anxiety. Cognitive rigidity, problems with emotion regulation, and intolerance of uncertainty associated with ASD can predispose this population to higher levels of anxiety and depression.

 Emotional regulation deficits may be a transdiagnostic phenomenon that underlies features of ASD as well as anxiety and other psychiatric comorbidities.

The Autism Comorbidity Interview (ACI) is a semi-structured interview that utilizes the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) with adaptation to increase validity in the ASD population. Additional screening questions and coding options were added to the ACI to help distinguish core features of ASD from features of other psychiatric disorders.

The ACI was used to assess psychiatric comorbidity in 109 children with ASD aged 5 to 17 years.

 Findings indicate that 72% of the children had at least one additional DSM-IV psychiatric diagnosis. Anxiety disorders were most common, followed by ADHD (

Assessment of comorbid psychiatric disorders

Screening instruments designed for psychiatric conditions in the general population may not adequately differentiate features of ASD and can result in overdiagnosis. However, there are several validated disorder-specific tools that have been specifically developed to assess for comorbid disorders in children and adults with ASD (

). Features of ASD can appear to overlap with symptoms of other conditions making it difficult to distinguish symptoms that relate to the core features of ASD versus symptoms of other psychiatric disorders (

General considerations for assessing psychiatric comorbidity in ASD

 It is important to establish an individual’s baseline for when he or she has functioned best. For psychiatric conditions that are episodic (eg, mood disorders) or those that appear later in development (eg, OCD, psychosis), it is important to distinguish baseline behaviors and functioning from distinct changes in symptoms that are expected with the onset of a co-occurring psychiatric condition.

 Assess for medical problems that can exacerbate emotional and behavioral symptoms, particularly in less verbal people.

 Some genetic syndromes are known to be associated with psychiatric conditions and behavioral phenotypes. This can help with more targeted screening (eg, fragile X syndrome has a higher prevalence of anxiety and ADHD, Williams syndrome has a higher prevalence of anxiety, and 22q11 deletion syndrome is associated with higher prevalence of psychosis).

4) Consider symptoms in the context of developmental level.

 Comorbid conditions should be considered if there are symptoms that are beyond what would be expected for an individual’s mental age and developmental level.

Using findings from their meta-analysis, vanSteensel and colleagues

 estimated that 40% of youth with ASD have a comorbid anxiety disorder. Risk factors for developing anxiety that are prevalent in ASD include social skill deficits, sensory sensitivity, cognitive rigidity, heightened physiological arousal, and difficulties regulating stress.

 Specific phobia tends to have an onset in childhood. In most cases the phenomenology of specific phobia in ASD tends to be similar to typically developing youth. However, people with developmental disabilities may also develop fears to unusual objects or situations, such as elevators, vacuum cleaners, etc.

Common phobias found in youth with ASD include loud noises, needles, and crowds. Sensory sensitivities can contribute to specific fears in autism, some of which may not rise to the level of meeting criteria for specific phobia but can contribute to impairment. For example, anxiety about eating food due to food textures, avoidance of clothing due to tactile sensitivity, or fear of loud objects such as vacuums and hairdryers due to noise sensitivity.

 Worry related to intense preoccupations, schedules, and environmental changes may be atypical features of anxiety that are important to recognize and ask patients about. Some of these features are captured by Kerns’s

 summation that they represent an “intolerance of uncertainty,” which can mark atypical anxiety in ASD.

Anxiety can present as perseverative questioning and reassurance seeking about an anticipated event or other worry. Repetitive questions used to obtain more information about a restricted interest should be distinguished from questions that are triggered by anxiety. People with ASD can have difficulty verbalizing internal states of anxiety or triggers for anxiety. For those who are non-communicative, an anxiety disorder may have to be considered by inference based on observation, such as persistent resistance to entering crowded rooms.

 Repetitive behaviors and restricted interests in ASD can be difficult to distinguish from the compulsions and obsessions of OCD. In OCD, obsessions are recurrent, intrusive thoughts that are distressing, and compulsive behaviors in OCD are bothersome, unwanted, and serve the function of attempting to alleviate the obsessional content.

Repetitive behaviors in ASD (eg, lining up objects, following the same routine, watching the same video) are generally a preferred or comforting activity, although they can lead to problematic behaviors or irritability when the person is interrupted or needs to stop. In addition, the most common forms of compulsions in OCD: hand washing, cleaning, making things “just right” are distinct from the typical repetitive behaviors of ASD, such as hand flapping, body rocking, and finger flicking.

People with ASD can have difficulty articulating obsessive thoughts and describing whether a behavior is aimed at reducing anxiety. The ACI adapted the criteria for OCD to allow caregivers to infer the mental experiences of people who exhibit compulsive behaviors. For example, caregivers could be asked if a compulsive behavior appeared to be aimed at reducing anxiety or linked to recurrent thoughts. Using this criteria Leyfer and colleagues

 found that 37% of their sample met criteria of OCD. In a different study by Simonoff and colleagues,

 the assessment tool did not allow for caregivers to make this inference and the prevalence of OCD was estimated at 8.2%.

 Diagnosis of social anxiety in ASD requires that a person with ASD is avoiding social interaction due to a fear of potential negative outcome rather than just a lack of interest in social interaction, which is a common core feature of ASD. In older higher-functioning youth social anxiety can develop as awareness of differences from peers increases.

ADHD is a common co-occurring condition with ASD and as such DSM-5 no longer prohibits ADHD to be diagnosed with ASD. Diagnosis of co-occurring ADHD can be challenging because symptoms of inattention, executive functioning problems, and social cognitive deficits are common in both conditions. It is important to distinguish features of inattention and impulsivity that may be inherent in ASD, such as distractibility related to a special interest, sensory seeking behaviors, or processing problems, from those that warrant an additional diagnosis of ADHD in children with ASD. The hyperactive-impulsive subtype of ADHD can also manifest in people with ASD and is best assessed in the context of the youth’s developmental age, expected activity level, and environmental demands.

Diagnosis of depression in neurotypical youth typically relies on self-report of mood symptoms such as feelings of sadness, hopelessness, or decreased self-esteem. Describing these internal states can be difficult for many people with ASD, particularly those with limited verbal skills.

 developed a framework for assessment of depression in ASD. For people with limited verbal skills or difficulties verbalizing feelings, increased self-injurious behavior, decreased self-care, labile moods, decreased interest in special interests, and regression of skills were observable behaviors associated with depression. For verbal youth with ASD, insight into ASD symptoms and their impact on functioning, awareness of being teased or being different from peers, social rejection, and low self-efficacy were risk factors for depression.

While their co-occurrence is uncommon, autism and psychosis have some symptom overlap, which can raise diagnostic questions. Pragmatic language deficits in ASD can include abrupt changes in topic, failure to provide context, and tangential comments, which can contribute to what appears to be a disorganized quality of language and thought process. When people with ASD are under stress they can have more disorganized and tangential speech, which is typically attributable to anxiety, problems with cognitive control, and pragmatic language deficits rather than underlying psychosis.

Moreover, people with ASD may use idiosyncratic language or scripted phrases from favorite movies or songs that appear out of context to the listener and therefore may sound disorganized or delusional. Strong convictions and overvalued ideas about their special interests may seem delusional. Difficulties with theory of mind and understanding the intentions of others may lead to distrust and paranoia but are best understood as the downstream effects of ASD core deficits, rather than a co-occurring psychosis.

There are currently no validated measures for assessing psychosis in ASD. Taking a detailed developmental history is key to distinguishing features of these two conditions. When psychosis occurs in ASD, the onset of psychotic symptoms is typically in adolescence or early adulthood and is associated with a change in functioning from baseline. Symptoms such as restricted affect, repetitive behaviors, tendency to disorganized speech when under stress, self-talk, or magical thinking, which have been chronic and present from a young age are more likely to be consistent with ASD rather than psychosis.

When baseline restricted interests become more morbid, illogical, and held with greater conviction with loss of reality testing, this may be more consistent delusional thought content, which may warrant an additional psychosis diagnosis. Larson and colleagues9 found that when psychosis co-occurs with ASD, the signs and symptoms of psychosis tended to be more transient and of shorter duration. As a result, the researchers noted that there tends to be a higher prevalence of psychotic disorder NOS (from DSM IV) diagnoses compared with schizophrenia diagnoses in part because of not meeting the duration of symptoms requirement.

Catatonic symptoms can develop in people with ASD with age of onset typically in adolescence.

 The occurrence of catatonia in autism is
	rare, but it is important to recognize given the benefit of early treatment and risk for life-threatening complications in severe cases. Diagnosis of catatonia in ASD can be challenging because echolalia, mutism, and stereotypic movements are common in both conditions.

Onset of catatonic symptoms in ASD may be gradual and in its early stages can present with a regression in self-care skills, reduction in speech, and difficulties initiating tasks. New onset of movement problems such as getting stuck part way through an action, difficulty initiating movements, immobility, increase in repetitive behaviors, difficulty crossing thresholds, and holding postures should raise suspicion for catatonia. Repetitive behaviors such as stereotypic movements and echolalia should not be counted toward a separate diagnosis of catatonia if they are consistent with an individual’s baseline symptoms of ASD.

Treatment of comorbid psychiatric conditions in ASD warrants a multimodal approach with contributions from caretaker education (applied behavioral analysis); psychotherapy; pharmacology; sensory, speech, and language interventions; and other disciplines depending on the individual’s history and presentation. Although a review of all of these modalities is beyond the scope of this article, some of the evidence and resources for CBT and pharmacotherapy for psychiatric comorbidity in ASD follow.

 CBT has been shown to reduce anxiety in children with ASD and anxiety disorders. Effective modifications to traditional CBT for youth with ASD have included increased parent involvement to promote generalization, incorporation of visual aids, making sessions highly structured and predictable, increased practice of skills, and explicit teaching of social skills as part of the therapy.

 Use of the child’s restricted interests can make the therapy more salient, help explain therapeutic concepts, create concrete metaphors, and reinforce participation.

ASD-specific CBT programs for anxiety include Multimodal Anxiety and Social Skills Intervention (MASSI), Face Your Fears, and Behavioral Interventions for Anxiety in Children With Autism (BIACA). Programs targeting executive functioning, mindfulness, and emotion regulation have also been found to reduce anxiety.

Pharmacological interventions. There are currently no medications for the core symptoms of ASD. Pharmacologic interventions for comorbid psychiatric conditions may help to alleviate associated symptoms and allow better engagement for the individual in educational and psychosocial treatments.

Targets for medication may include but are not limited to anxiety, impulsivity, hyperactivity, sleep problems, mood instability, depression, aggression, and self-injurious behavior. The American Academy of Child and Adolescent Psychiatry (AACAP) Practice Parameter on ASD

 provides a summary of ran-
	domized controlled trials of medications to treat comorbid psychiatric conditions in ASD; the AACAP

 provides an overview of medication approaches by symptom area and guidelines for parent-provider discussion. Both are available for free download at

Dr Siegel is Vice President Medical Affairs, Developmental Disorders Service, Maine Behavioral Healthcare, Portland, ME; he is also Associate Professor of Psychiatry and Pediatrics, Tufts University School of Medicine, Boston, MA. Dr Collins is a Child and Adolescent Psychiatrist, Developmental Disorders Program, Sprint Harbor Hospital, Center for Autism and Developmental Disorders, Maine Behavioral Healthcare. The authors report no conflicts of interest concerning the subject matter of this article.

 Baio J, Wiggins L, Christensen DL, et al. Prevalence of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. 

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Autism Spectrum Disorder: Parents’ Medication Guide

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While the core features of autism impair functioning, a significant source of further impairment is comorbid psychiatric disorders.

Author | Heidi C. Collins, MD

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