Comorbidities and autism

I recently wrote an editorial about comorbidities in autism which was published in Frontiers in Psychiatry on November 2020. One of the reasons for writing the editorial was to honor the memory of my grandson, Bertrand, who could have served as the poster child for comorbidities in autism. My best intentions were foiled as the Frontiers Journal does not allow for acknowledgements. I am providing below the first few paragraphs of the rather long editorial. Those interested in reading the whole article or examining its references can do so following the clickable link at Researchgate. The editorial goes as follows:

The presence of a chronic disorder that co-occurs, at the same time or in tandem, with a primary disease is a comorbidity. Defining the presence and natural history of comorbiditiesis important as it serves to better inform treatment and prognosis (1). For many individuals, comorbidities worsen the way they feel, behave, and think about themselves. Indeed, comorbidities add a multidimensional component to both diagnosis and treatment that colors the expectations of patients as well as their treating physicians.

By themselves, comorbidities are associated with worse outcomes and increased health needs.The presence of co-occurring medical conditions confers those affected with a higher level of morbidity, increased risk of depression, and reduced level of social well-being (2). These patients require more frequent and targeted clinical management (e.g., to avoid dangers of polypharmacy), services planning (e.g., coordination between various health care professionals), and financing. The more precise our understanding of a disease and its comorbidities the better the clinical care and health services that can be provided. It should come as no surprise that treatment of comorbidities generally improves the quality of life of affected patients.

The abundance of chronic conditions (e.g., diabetes, arthritis, obesity, depression) in modern medicine makes comorbidity the norm rather than the exception. In 2014, approximately 42% of adult Americans had multiple chronic conditions (3). Indeed, almost 77% of Medicare spending goes to people with multimorbid conditions; that is, the presence of 2 or more chronic disorders(4). A population-based survey in Sweden revealed that half of individuals with ASD (9-year-oldtwins born between 1992 and 2001) had four or more coexisting disorders while only 4% did not have a concomitant disorder (5). Considering that ASD is a lifelong condition, affecting 1 ofevery54 children, the subject of comorbidities is of great importance for patient-centered health research,especially so as the mean age of our population increases (6–8).

In ASD, comorbidities do not occur evenly but tend to cluster into different subgroups. A recent study reported that ASD individuals can be subtyped according to whether they exhibit seizures, multisystem disorders, psychiatric disorders, or whether they lack a defined comorbidity (9). External validation of the different clusters was derived from within group commonalities in medical trajectories and an inability to generalize results among the different subgroups. The study demonstrates the usefulness of thinking about ASD as being divided into “essential or uncomplicated” and “complex” subgroups each with a different outcome and recurrence risk [e.g., (10)].

Comorbidities in ASD manifest as impairments outside of its core diagnostic features; the latter being deficits in social communication/interaction, and restricted, repetitive patterns of behavior, interests, or activities, including sensory processing difficulties (11). Epilepsy, psychiatric/behavioral complaints, and gastrointestinal (GI) disorders are common comorbidities of ASD, especially in subjects with intellectual disability (ID) (12). Comorbidities frequently manifest in preschool years (Muratoriet al.) and their presence may be the best predictor of maladaptive behavior, respective of ASD symptom severity, presence of ID or limitations in adaptive functioning (Skwerer et al.).

The prevalence of comorbidities varies widely, from study to study, probably pointing to the fact that ASD is not a unitary disorder but a spectrum involving different pathophysiologies.Lumping patients into a single group tends to average out significant differences within a study population. Conclusions from these prevalence studies should be taken cautiously as research designs tend to exhibit multiple limitations. Indeed,when interpreting results, one must consider the variability ingrained in different ascertainment methods and the lack of available specialized consultative care in some study centers. In addition, many prevalence studies on comorbidities use small patient samples and/or fail to address the impact of demographic,socioeconomic, ethnic, and geographical factors on diagnosis.

In ASD, the expression of comorbidities stemming from any given organ system can take multiple forms. For GI comorbidities this may involve gastroesophageal reflux (GERD), constipation,diarrhea, food allergies, colitis, ulcers, and inflammatory bowel disease (13). These are all common disorders, readily observed in the general population and frequently associated with ID,sleep problems, behavioral disorders, and even connective tissue disorders like Ehlers-Danlos syndrome (EDS), which are also comorbid with ASD (Penzol et al.; Baeza-Velasco et al.). Associated behaviors may exhibit varying relationships to GI symptoms at different ages, a fact having important implications for medical care (Cawthrope; Ferguson et al.). In effect, treating GI disorders may help alleviate a broad array of disorders(e.g., mental, behavioral, sleep) in the multimorbid ASD patient (Neuhaus et al.).

8 responses to “Comorbidities and autism

  1. Thank you Dr. Casanova for sharing your article on ‘Comorbidities and Autism’. My 14 year old son is on high functioning ASD, with ADHD and treatment resistant OCD. In your book ‘Autism and Imaging Devices’, you shared a case of a 20 year old with ASD and OCD who was successfully treated with nuerofeedback. Would you recommend rTMS or nuerofeedback as a potential treatment option for my son?


    • We have studies proving the synergistic action of TMS and neurofeedback together. However, TMS remains an experimental therapy for ASD and the FDA has not approved the same. Finding a place that may be able to provide the same remains difficult. Otherwise neurofeedback is a common technique and has been approved for ADHD. Results are usually seen after many interventions (about 40) and there are no major side effects to the same. Thank you for sharing your thoughts and impressed that you read our book.


      • Thank you for your response! I would like to get in touch with Dr. Casanova to understand how my son can participate in the research studies related to Autism and TMS. Can you please share his email?


        Chaps Attota



      • I unfortunately retired and ever since the beginning of COVID stopped all clinical trials. We lacked support for our TMS/neurofeedback efforts. My best recommendation would be to go to and see what trials are available. Hopefully one will be near you. It is also a long shot but you may want to see what is happening at the Seattle Children research Institute. They are well known for a lot of their autism related efforts. Best regards, Manuel


      • Thank you for your response Dr. Casanova. I checked both UW Autism and Clinical Trials sites, there are no active TMS or Neurofeedback pediatric studies in the US at the moment, though there is one in pre-enrollment stage at Stanford University. If it wouldn’t be too much trouble for you, I was wondering if you are willing to speak to me briefly over the phone to point to me some well known researchers in this field, so I can pursue this further? I would greatly appreciate your help!


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