Over 70% of children with ASD show at least one comorbid condition, and 41% of them show two or more.
Among the different comorbidities, we can list:
Here I will briefly describe some conditions commonly found as overlapping with ASD.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by symptoms that fall under two main categories:
People with ADHD may show symptoms that fall under one of these two categories only, or symptoms of both categories. These symptoms begin to be evident between 3 and 6 years of age, and are surely present by 12 years of age. A diagnosis of ADHD is usually made around 7 years of age, but it is not rare to recognize ADHD as adolescents or adults, especially if you have only inattentive symptoms (called ADD).
ADHD is a common condition. About 5% of children and adolescents, and 2.5% of adults worldwide have ADHD. It also often overlaps with autism. In fact, up to 50% of children with ADHD also meet diagnostic criteria for autism, and up to 80% of children with autism meet criteria for ADHD.
ADHD is highly heritable (around 80%), and similarly to autism, no single factor is necessary or sufficient to cause ADHD. Rather, ADHD is considered to arise in most cases from several genetic and environmental factors that each have a small individual effect and act together to increase the probability of developing symptoms characteristic of ADHD. This multifactorial is evident in combinations of comorbidities, brain alterations, as well as strengths and difficulties in cognition and everyday functioning that are uniquely different among people with ADHD. Single curative treatments for ADHD do not exist, and are not necessary, but rather different options are available for treatment of uncomfortable and unwanted symptoms. For example, medications are efficacious and normally well tolerated, but there are also different non-pharmacological approaches available (e.g. diet and physical exercise).
ADHD can have a significant impact on certain aspects of someone’s life, and it has been associated to a higher probability of having difficulties in school and at maintaining a job, of having serious accidents, of developing addictions, of committing crimes or having troubles with societal rules in general. Nevertheless, people with ADHD may also not experience any major accident or have any troublesome issue with society, but rather cope with their symptoms and have a very successful life. For instance, we can mention some very successful people with ADHD, like Jim Carrey, Will Smith, Michael Jordan or Michael Phelps.
Depression is a common mental-health condition, affecting more than 264 million people of all ages worldwide, women more than men.
It is characterised by symptoms like:
feelings of hopelessness, obsessive thoughts, social isolation, sleep problems, aggression, self-injury, irritability and suicidal thoughts.
physical symptoms, such as always feeling tired, restlessness and stomachaches.
Depression in also more common in people with autism, with more than 5 in 10 adults with autism reporting to have had depression, and unaffected siblings of people with autism have a 40% higher probability to experience depression. Adolescents with autism are 4 times more likely to experience depression than their peers are, and adults with autism are over 9 times more likely to consider suicide than the general population.
The cause is likely a mix of genetic and environmental factors, and we still don’t know how autism figures in that mix.
In terms of genetics, we have indicators of a contribution from studies on unaffected siblings of people with ASD (having a 40% higher probability to experience depression).
In terms of environment, social stress seems to be highly correlated with depressive symptoms, especially for people with high levels of social and communication skills. In particular, being bullied by their peers, non being fully understood and supported by their family, being isolated, and feeling lonely are all factors that contribute to depression. Many people with autism also intensely focused interests, and a propensity to focus on negative emotions, sad or undesirable experiences. This, accompanied by stigma from peers and family, makes them experience trauma more easily, and increases their chances of having depressive symptoms.
Depression in people with autism is more common during adolescence and young adulthood, and its symptoms are known to increase across adolescence. This is not surprising given the socially stressful environment experienced in adolescence. Given the effect of depression on their development of social skills, communication, coping abilities, independence and daily living skills, it is crucial that parents and paediatricians can also be coached to look out for signs of depression in children with autism.
I want to shift the focus from comorbid psychiatric conditions to a physical condition that often overlaps with autism.
The association between gastrointestinal (GI) problems and autism was already noted by Leo Kanner, one of the first psychiatrists to describe autism. 7 out of the 11 children that Kanner described in his landmark article had eating/feeding or dietary problems.
Most common GI symptoms include overproduction of intestinal gasses/flatulence (60%), bloating (38%), abdominal pain (378%), diarrhea (28%), burping/belching (25%), gastroesophageal reflux symptoms (16%), and constipation (10%).
Disorders of the GI tract affect up to 84% of children with autism, compared with 9% to 37% for children without autism. Severity of these GI symptoms is strongly associated to severity of autism symptoms, like difficulties in processing sensory stimuli, motor problems and altered social behaviours. At the same time, improved gut health has been associated to reduced symptoms of autism!
The causes of this association are still not fully clear. From the autism perspective, it is true that many children with autism are very selective with the foods they eat, with a preference for highly processed foods, while they eat fewer fruits, vegetables and whole grains. Thus, they may have nutritionally poor diets, leading to weight-related health issues like obesity, high blood pressure (hypertension) and diabetes, as frequently observed in adults with autism.
From the GI perspective, many studies are focussing now on the microbiome (the genetic material of micro-organisms that can be found in the human gut) and the microbiota-gut-brain axis (the bidirectional communication between the gut, and its composition of micro-organisms, and the brain that directly influences behaviour and cognition). The largest population of microbes on the human body resides in the GI tract and consists of more than 60 genera, containing more cells than the human body. The gut microbiome influences many aspects of our health, including the brain. Thus, it is not surprising that disruptions to the microbiota-gut-brain axis has recently become a key aspect of autism research.
These studies identified different types of fermenting microbes (like the Prevotella genus) that are lacking in the gut of children, and provided targets for treatment of both GI and autism symptoms through diet. For instance, pre- and probiotic treatment showed promising results in relation to symptoms of autism, but also gluten-free diets (as alterations in the digestion and absorption of carbohydrates could also explain some of the GI problems reported in people with autism) and multivitamin supplementation.
Cawthorpe, D. Comprehensive Description of Comorbidity for Autism Spectrum Disorder in a General Population. Perm J 21, doi:10.7812/TPP/16-088 (2017).
Matson, J. L. & Goldin, R. L. Comorbidity and autism: Trends, topics and future directions. Res Autism Spect Dis 7, 1228-1233, doi:10.1016/j.rasd.2013.07.003 (2013).
Matson, J. L. & Cervantes, P. E. Commonly studied comorbid psychopathologies among persons with autism spectrum disorder. Res Dev Disabil 35, 952-962, doi:10.1016/j.ridd.2014.02.012 (2014).
Simonoff, E. et al. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry 47, 921-929, doi:10.1097/CHI.0b013e318179964f (2008).
Gargaro, B. A., Rinehart, N. J., Bradshaw, J. L., Tonge, B. J. & Sheppard, D. M. Autism and ADHD: how far have we come in the comorbidity debate? Neurosci Biobehav Rev 35, 1081-1088, doi:10.1016/j.neubiorev.2010.11.002 (2011).
Mannion, A. & Leader, G. An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder: A two year follow-up. Res Autism Spect Dis 22, 20-33, doi:10.1016/j.rasd.2015.11.002 (2016).
Matson, J. L. & Williams, L. W. Differential diagnosis and comorbidity: distinguishing autism from other mental health issues. Neuropsychiatry-Lond 3, 233-243, doi:10.2217/Npy.13.1 (2013).
Leyfer, O. T. et al. Comorbid psychiatric disorders in children with autism: Interview development and rates of disorders. J Autism Dev Disord 36, 849-861, doi:10.1007/s10803-006-0123-0 (2006).
Horvath, K. & Perman, J. A. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr 14, 583-587 (2002).
Tuchman, R. & Rapin, I. Epilepsy in autism. Lancet Neurol 1, 352-358 (2002).
Sokolova, E. et al. A Causal and Mediation Analysis of the Comorbidity Between Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). J Autism Dev Disord 47, 1595-1604, doi:10.1007/s10803-017-3083-7 (2017).
Chiang, H. L. & Gau, S. S. Comorbid psychiatric conditions as mediators to predict later social adjustment in youths with autism spectrum disorder. J Child Psychol Psychiatry 57, 103-111, doi:10.1111/jcpp.12450 (2016).
Doshi-Velez, F., Ge, Y. & Kohane, I. Comorbidity clusters in autism spectrum disorders: an electronic health record time-series analysis. Pediatrics 133, e54-63, doi:10.1542/peds.2013-0819 (2014).
Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22. doi: 10.1186/1471-230X-11-22. PMID: 21410934; PMCID: PMC3072352.
Chidambaram SB, Tuladhar S, Bhat A, Mahalakshmi AM, Ray B, Essa MM, Bishir M, Bolla SR, Nanjaiah ND, Guillemin GJ, Qoronfleh MW. Autism and Gut-Brain Axis: Role of Probiotics. Adv Neurobiol. 2020;24:587-600. doi: 10.1007/978-3-030-30402-7_21. PMID: 32006375.
Hsiao EY. Gastrointestinal issues in autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):104-11. doi: 10.1097/HRP.0000000000000029. PMID: 24614765.
Wasilewska, J., & Klukowski, M. (2015). Gastrointestinal symptoms and autism spectrum disorder: links and risks - a possible new overlap syndrome. Pediatric health, medicine and therapeutics, 6, 153–166. https://doi.org/10.2147/PHMT.S85717
Among the different comorbidities, we can list:
- Developmental and mental-health conditions, as ADHD, intellectual disability, anxiety, Oppositional Defiant Disorder, bipolar disorder, language delay or depression.
- Medical conditions, as gastrointestinal symptoms, motor difficulties, sleep problems and epilepsy.
- Genetic conditions, as fragile X syndrome, down syndrome and tuberous sclerosis complex.
Here I will briefly describe some conditions commonly found as overlapping with ASD.
ADHD
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by symptoms that fall under two main categories:
- hyperactivity and impulsivity: like being constantly fidgeting, being unable to sit still, talking or moving too much, being unable to wait your turn, even in conversations, acting without thinking, or having little or no sense of danger.
- inattention: like being easily distracted, making careless mistakes, appearing forgetful, losing or misplacing things very often, being unable to stick to tasks or to listen and carry out instructions, or having difficulties organising tasks.
People with ADHD may show symptoms that fall under one of these two categories only, or symptoms of both categories. These symptoms begin to be evident between 3 and 6 years of age, and are surely present by 12 years of age. A diagnosis of ADHD is usually made around 7 years of age, but it is not rare to recognize ADHD as adolescents or adults, especially if you have only inattentive symptoms (called ADD).
ADHD is a common condition. About 5% of children and adolescents, and 2.5% of adults worldwide have ADHD. It also often overlaps with autism. In fact, up to 50% of children with ADHD also meet diagnostic criteria for autism, and up to 80% of children with autism meet criteria for ADHD.
ADHD is highly heritable (around 80%), and similarly to autism, no single factor is necessary or sufficient to cause ADHD. Rather, ADHD is considered to arise in most cases from several genetic and environmental factors that each have a small individual effect and act together to increase the probability of developing symptoms characteristic of ADHD. This multifactorial is evident in combinations of comorbidities, brain alterations, as well as strengths and difficulties in cognition and everyday functioning that are uniquely different among people with ADHD. Single curative treatments for ADHD do not exist, and are not necessary, but rather different options are available for treatment of uncomfortable and unwanted symptoms. For example, medications are efficacious and normally well tolerated, but there are also different non-pharmacological approaches available (e.g. diet and physical exercise).
ADHD can have a significant impact on certain aspects of someone’s life, and it has been associated to a higher probability of having difficulties in school and at maintaining a job, of having serious accidents, of developing addictions, of committing crimes or having troubles with societal rules in general. Nevertheless, people with ADHD may also not experience any major accident or have any troublesome issue with society, but rather cope with their symptoms and have a very successful life. For instance, we can mention some very successful people with ADHD, like Jim Carrey, Will Smith, Michael Jordan or Michael Phelps.
DEPRESSION
It is characterised by symptoms like:
feelings of hopelessness, obsessive thoughts, social isolation, sleep problems, aggression, self-injury, irritability and suicidal thoughts.
physical symptoms, such as always feeling tired, restlessness and stomachaches.
Depression in also more common in people with autism, with more than 5 in 10 adults with autism reporting to have had depression, and unaffected siblings of people with autism have a 40% higher probability to experience depression. Adolescents with autism are 4 times more likely to experience depression than their peers are, and adults with autism are over 9 times more likely to consider suicide than the general population.
The cause is likely a mix of genetic and environmental factors, and we still don’t know how autism figures in that mix.
In terms of genetics, we have indicators of a contribution from studies on unaffected siblings of people with ASD (having a 40% higher probability to experience depression).
In terms of environment, social stress seems to be highly correlated with depressive symptoms, especially for people with high levels of social and communication skills. In particular, being bullied by their peers, non being fully understood and supported by their family, being isolated, and feeling lonely are all factors that contribute to depression. Many people with autism also intensely focused interests, and a propensity to focus on negative emotions, sad or undesirable experiences. This, accompanied by stigma from peers and family, makes them experience trauma more easily, and increases their chances of having depressive symptoms.
Depression in people with autism is more common during adolescence and young adulthood, and its symptoms are known to increase across adolescence. This is not surprising given the socially stressful environment experienced in adolescence. Given the effect of depression on their development of social skills, communication, coping abilities, independence and daily living skills, it is crucial that parents and paediatricians can also be coached to look out for signs of depression in children with autism.
GASTROINTESTINAL PROBLEMS
The association between gastrointestinal (GI) problems and autism was already noted by Leo Kanner, one of the first psychiatrists to describe autism. 7 out of the 11 children that Kanner described in his landmark article had eating/feeding or dietary problems.
Most common GI symptoms include overproduction of intestinal gasses/flatulence (60%), bloating (38%), abdominal pain (378%), diarrhea (28%), burping/belching (25%), gastroesophageal reflux symptoms (16%), and constipation (10%).
Disorders of the GI tract affect up to 84% of children with autism, compared with 9% to 37% for children without autism. Severity of these GI symptoms is strongly associated to severity of autism symptoms, like difficulties in processing sensory stimuli, motor problems and altered social behaviours. At the same time, improved gut health has been associated to reduced symptoms of autism!
The causes of this association are still not fully clear. From the autism perspective, it is true that many children with autism are very selective with the foods they eat, with a preference for highly processed foods, while they eat fewer fruits, vegetables and whole grains. Thus, they may have nutritionally poor diets, leading to weight-related health issues like obesity, high blood pressure (hypertension) and diabetes, as frequently observed in adults with autism.
From the GI perspective, many studies are focussing now on the microbiome (the genetic material of micro-organisms that can be found in the human gut) and the microbiota-gut-brain axis (the bidirectional communication between the gut, and its composition of micro-organisms, and the brain that directly influences behaviour and cognition). The largest population of microbes on the human body resides in the GI tract and consists of more than 60 genera, containing more cells than the human body. The gut microbiome influences many aspects of our health, including the brain. Thus, it is not surprising that disruptions to the microbiota-gut-brain axis has recently become a key aspect of autism research.
These studies identified different types of fermenting microbes (like the Prevotella genus) that are lacking in the gut of children, and provided targets for treatment of both GI and autism symptoms through diet. For instance, pre- and probiotic treatment showed promising results in relation to symptoms of autism, but also gluten-free diets (as alterations in the digestion and absorption of carbohydrates could also explain some of the GI problems reported in people with autism) and multivitamin supplementation.
Future work on early detection and stratification of ASD should carefully take into consideration comorbidities by integrating clinical and biological measures assessing signs and symptoms for different conditions. This could significantly improve our understanding of the underlying biological mechanisms and precursors to the emergence of specific or overlapping symptoms of this broader range of conditions.
REFERENCES
Cawthorpe, D. Comprehensive Description of Comorbidity for Autism Spectrum Disorder in a General Population. Perm J 21, doi:10.7812/TPP/16-088 (2017).
Matson, J. L. & Goldin, R. L. Comorbidity and autism: Trends, topics and future directions. Res Autism Spect Dis 7, 1228-1233, doi:10.1016/j.rasd.2013.07.003 (2013).
Matson, J. L. & Cervantes, P. E. Commonly studied comorbid psychopathologies among persons with autism spectrum disorder. Res Dev Disabil 35, 952-962, doi:10.1016/j.ridd.2014.02.012 (2014).
Simonoff, E. et al. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry 47, 921-929, doi:10.1097/CHI.0b013e318179964f (2008).
Gargaro, B. A., Rinehart, N. J., Bradshaw, J. L., Tonge, B. J. & Sheppard, D. M. Autism and ADHD: how far have we come in the comorbidity debate? Neurosci Biobehav Rev 35, 1081-1088, doi:10.1016/j.neubiorev.2010.11.002 (2011).
Mannion, A. & Leader, G. An investigation of comorbid psychological disorders, sleep problems, gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder: A two year follow-up. Res Autism Spect Dis 22, 20-33, doi:10.1016/j.rasd.2015.11.002 (2016).
Matson, J. L. & Williams, L. W. Differential diagnosis and comorbidity: distinguishing autism from other mental health issues. Neuropsychiatry-Lond 3, 233-243, doi:10.2217/Npy.13.1 (2013).
Leyfer, O. T. et al. Comorbid psychiatric disorders in children with autism: Interview development and rates of disorders. J Autism Dev Disord 36, 849-861, doi:10.1007/s10803-006-0123-0 (2006).
Horvath, K. & Perman, J. A. Autistic disorder and gastrointestinal disease. Curr Opin Pediatr 14, 583-587 (2002).
Tuchman, R. & Rapin, I. Epilepsy in autism. Lancet Neurol 1, 352-358 (2002).
Sokolova, E. et al. A Causal and Mediation Analysis of the Comorbidity Between Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). J Autism Dev Disord 47, 1595-1604, doi:10.1007/s10803-017-3083-7 (2017).
Chiang, H. L. & Gau, S. S. Comorbid psychiatric conditions as mediators to predict later social adjustment in youths with autism spectrum disorder. J Child Psychol Psychiatry 57, 103-111, doi:10.1111/jcpp.12450 (2016).
Doshi-Velez, F., Ge, Y. & Kohane, I. Comorbidity clusters in autism spectrum disorders: an electronic health record time-series analysis. Pediatrics 133, e54-63, doi:10.1542/peds.2013-0819 (2014).
Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism--comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011 Mar 16;11:22. doi: 10.1186/1471-230X-11-22. PMID: 21410934; PMCID: PMC3072352.
Chidambaram SB, Tuladhar S, Bhat A, Mahalakshmi AM, Ray B, Essa MM, Bishir M, Bolla SR, Nanjaiah ND, Guillemin GJ, Qoronfleh MW. Autism and Gut-Brain Axis: Role of Probiotics. Adv Neurobiol. 2020;24:587-600. doi: 10.1007/978-3-030-30402-7_21. PMID: 32006375.
Hsiao EY. Gastrointestinal issues in autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):104-11. doi: 10.1097/HRP.0000000000000029. PMID: 24614765.
Wasilewska, J., & Klukowski, M. (2015). Gastrointestinal symptoms and autism spectrum disorder: links and risks - a possible new overlap syndrome. Pediatric health, medicine and therapeutics, 6, 153–166. https://doi.org/10.2147/PHMT.S85717
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