Conditions comorbid to autism

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Autism spectrum disorder (ASD) or simply autism is classified as a neurodevelopmental disorder that begins in early childhood, persists throughout adulthood, and is characterized by difficulties in social communication and restricted, repetitive patterns of behavior. [1] There are many conditions comorbid to autism, such as attention deficit hyperactivity disorder, anxiety disorders, and epilepsy.

Contents

In medicine, comorbidity is the presence of one or more additional conditions co-occurring with the primary one, or the effect of such additional conditions. Distinguishing between autism and other diagnoses can be challenging because the traits of autism often overlap with symptoms of other conditions, and the characteristics of autism make traditional diagnostic procedures difficult. [2] [3]

Autism is associated with several genetic disorders, [4] perhaps due to an overlap in genetic causes.[ medical citation needed ] About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome, [5] a category referred to as syndromic autism.

Approximately 8 in 10 people with autism suffer from a mental health problem in their lifetime, in comparison to 1 in 4 of the general population that suffers from a mental health problem in their lifetimes.[ medical citation needed ]

Euler diagram showing overlapping clinical phenotypes in genes associated with monogenic forms of autism, dystonia, epilepsy and schizophrenia: .mw-parser-output .legend{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .legend-color{display:inline-block;min-width:1.25em;height:1.25em;line-height:1.25;margin:1px 0;text-align:center;border:1px solid black;background-color:transparent;color:black}.mw-parser-output .legend-text{} Genes associated with epilepsy Genes associated with schizophrenia Genes associated with autism spectrum disorder Genes associated with dystonia Overlapping clinical phenotypes in genes associated with monogenic forms of autism spectrum disorder (ASD), dystonia, epilepsy and schizophrenia.svg
Euler diagram showing overlapping clinical phenotypes in genes associated with monogenic forms of autism, dystonia, epilepsy and schizophrenia:
  Genes associated with epilepsy
  Genes associated with schizophrenia
  Genes associated with autism spectrum disorder
  Genes associated with dystonia

Comorbid conditions

Anxiety

Anxiety disorders are common among children and adults with autism. Symptoms are likely affected by age, level of cognitive functioning, degree of social impairment, and autism-specific difficulties. Many anxiety disorders, such as social anxiety disorder and generalized anxiety disorder, are not commonly diagnosed in people with autism because such symptoms are better explained by autism itself, and it is often difficult to tell whether symptoms such as compulsive checking are part of autism or a co-occurring anxiety problem. The prevalence of anxiety disorders in children with autism has been reported to be anywhere between 11% and 84%; the wide range is likely due to differences in the ways the studies were conducted. [6]

A systematic review summarized available evidence on interventions to reduce anxiety in school children with autism. Of the 24 studies reviewed, 22 used a cognitive behavioral therapy (CBT) approach. The review found that CBT was moderately to highly effective at reducing anxiety in school children with autism, but that effects varied depending on whether they were reported by clinicians, parents or self-reported. Treatments involving parents and one-on-one compared to group treatments were more effective. [7]

Attention deficit hyperactivity disorder

The diagnosis manual DSM-IV did not allow the co-diagnosis of autism and attention deficit hyperactivity disorder (ADHD). However, following years of clinical research, the DSM-5 released in 2013 removed this prohibition of co-morbidity. Thus, individuals with autism may also have a diagnosis of ADHD, with the modifiers of a predominantly inattentive, hyperactive, combined, or not otherwise specified presentation. Clinically significant symptoms of these two conditions commonly co-occur, and children with both sets of symptoms may respond poorly to standard ADHD treatments. Individuals with autism may benefit from additional types of medications. [8] The term AuDHD is sometimes used for those with both autism and ADHD. [9] There are also studies suggesting noticeable differences in presenting symptoms by gender which can complicate diagnosis, especially in adulthood. [10]

Avoidant/restrictive food intake disorder

Avoidant/restrictive food intake disorder (ARFID) is a feeding or eating disorder in which individuals significantly limit the volume or variety of foods they consume, causing malnutrition, weight loss, and psychosocial problems. [11] A 2023 review concluded that "there is considerable overlap between ARFID and autism," finding that 8% to 55% of children diagnosed with ARFID were autistic. [12] Unlike eating disorders such as anorexia nervosa and bulimia, body image disturbance is not a root cause. Individuals with ARFID may have trouble eating due to the sensory characteristics of food (appearance, smell, texture, or taste); executive function disregulation; fears of choking or vomiting; low appetite; or a combination of these factors. [13]

Bipolar disorder

Bipolar disorder, or manic-depression, is itself often claimed to be comorbid with a number of conditions, including autism. [14]

Bowel disease

Gastrointestinal symptoms are a common comorbidity in autistic people, even though the underlying mechanisms are largely unknown. The most common gastrointestinal symptoms reported by proprietary tool developed and administered by Mayer, Padua, and Tillisch (2014) are abdominal pain, constipation, diarrhea and bloating, reported in at least 25 percent of participants. [15] Carbohydrate digestion and transport is impaired in individuals with autism, which is thought to be attributed to functional disturbances that cause increased intestinal permeability, deficient enzyme activity of disaccharides, increased secretin-induced pancreatico-biliary secretion, and abnormal fecal flora Clostridia taxa.[ medical citation needed ] Altered gastrointestinal function accompanied by pain may induce feeding issues and increase perceived negative behaviors, including self injury, in individuals with autism.[ medical citation needed ]

Depression

Major depressive disorder has been shown by several studies to be one of the most common comorbid conditions in those who are autistic, [16] [17] and is thought to develop and occur more in high-functioning individuals during adolescence, when the individual develops greater insight into their differences from others.[ medical citation needed ] In addition, the presentation of depression in autism can depend on the level of cognitive functioning in the individual, with lower functioning children displaying more behavioral issues and higher functioning children displaying more traditional depressive symptoms. [2]

A 2019 meta-analysis identified autistic people as being four times more likely to have depression than non-autistic people, [18] with approximately 40% of autistic adults having depression. [19]

Developmental coordination disorder (dyspraxia)

The initial accounts of Asperger syndrome [20] and other diagnostic schemes include descriptions of developmental coordination disorder. Children with autism may be delayed in acquiring motor skills that require motor dexterity, such as bicycle riding or opening a jar, and may appear awkward or "uncomfortable in their own skin". They may be poorly coordinated, or have an odd or bouncy gait or posture, poor handwriting, other hand/dexterity impairments, or problems with visual-motor integration, visual-perceptual skills, and conceptual learning. [20] [21] They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder, balance, tandem gait, and finger-thumb apposition. [20]

Epilepsy

Autism is also associated with epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder. [22] One in four autistic children develops seizures, often starting either in early childhood or adolescence. [23] Seizures, caused by abnormal electrical activity in the brain, can produce a temporary loss of consciousness (a "blackout"), a body convulsion, unusual movements, or staring spells. Sometimes a contributing factor is a lack of sleep or a high fever. An EEG can help confirm the seizure's presence. Typically, onset of epilepsy occurs before age five or during puberty, [24] and is more common in females and individuals who also have a comorbid intellectual disability.

Fetal alcohol spectrum disorder

Fetal alcohol spectrum disorders (FASD) are a group of conditions that can occur in a person who is exposed to alcohol during gestation. [25] Evidence on the link between FASD and autism is limited. [26] Although results from studies are mixed, it is estimated that 2.6% of children with an FASD have an autism as well, a rate almost two times higher than that reported in the general US population. [26] However, there is no information on the prevalence of FASD amongst those with autism.

Fragile X syndrome

Fragile X syndrome is the most common inherited form of intellectual disability. It was so named because one part of the X chromosome has a defective piece that appears pinched and fragile when under a microscope. Fragile X syndrome represents an estimated 1% to 6% of all autism cases.[ medical citation needed ]

Gender dysphoria

Gender dysphoria is a diagnosis given to transgender people who experience discomfort related to their gender identity. [27] Autistic people are more likely to experience gender dysphoria. [28] Around 20% of gender identity clinic-assessed individuals reported characteristics of autism. [29]

Hypermobility spectrum disorder and Ehlers–Danlos syndromes

Studies have confirmed a link between hereditary connective tissue disorders such as Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorder (HSD) with autism, as a comorbidity and a co-occurrence within the same families. [30]

Intellectual disability

The fraction of autistic individuals who also meet criteria for intellectual disability has been reported as anywhere from 25% to 70%. This wide variation illustrates the difficulty of assessing intelligence in autistic individuals. [31] Learning disabilities are also highly comorbid in individuals with autism. Approximately 25–75% of individuals with autism also have some degree of learning disability, [32] although the types of learning disability vary depending on the specific strengths and weaknesses of the individual.

A 2006 review questioned the common assumption that most children with autism have an intellectual disability. [33]

The CDC states that based on information from 11 reporting states 46% of people with autism have above 85 IQ. [34]

Mitochondrial diseases

The central player in bioenergetics is the mitochondrion. Mitochondria produce about 90% of cellular energy, regulate cellular redox status, produce ROS, maintain Ca2+
 homeostasis, synthesize and degrade high-energy biochemical intermediates, and regulate cell death through activation of the mitochondrial permeability transition pore (mtPTP). When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole organ systems begin to fail.

Mitochondrial diseases are a heterogeneous group of disorders that can affect multiple organs with varying severity. Symptoms may be acute or chronic with intermittent decompensation. Neurological manifestations include encephalopathy, stroke, cognitive regression, seizures, cardiopathies [35] (cardiac conduction defects, hypertensive heart disease, cardiomyopathy, [36] etc...), diabetes, visual and hearing loss, organ failure, neuropathic pain and peripheral neuropathy.

Mitochondrial disease is estimated to affect less than 0.1% of the general population. [37] Approximately 5% of autistic children meet the criteria for classical mitochondrial dysfunction. [38] It is unclear why this mitochondrial disease occurs, considering that only 23% of children with both autism and mitochondrial disease present with mitochondrial DNA abnormalities. [38]

Neurofibromatosis type I

Autism is also associated with neurofibromatosis type I (NF-1). [39] NF-1 is a complex multi-system human disorder caused by the mutation of a gene on chromosome 17 that is responsible for production of a protein, called neurofibromin 1, which is needed for normal function in many human cell types. NF-1 causes tumors along the nervous system which can grow anywhere on the body. NF-1 is one of the most common genetic disorders and is not limited to any person's race or sex. NF-1 is an autosomal dominant disorder, which means that mutation or deletion of one copy (or allele) of the NF-1 gene is sufficient for the development of NF-1, although presentation varies widely and is often different even between relatives affected by NF-1.

Neuroinflammation and immune disorders

The role of the immune system and neuroinflammation in the development of autism is controversial. Until recently, there was scant evidence supporting immune hypotheses, but research into the role of immune response and neuroinflammation may have important clinical and therapeutic implications. The exact role of heightened immune response in the central nervous system (CNS) of patients with autism is uncertain, but may be a primary factor in triggering and sustaining many of the comorbid conditions associated with autism. Recent studies indicate the presence of heightened neuroimmune activity in both the brain tissue and the cerebrospinal fluid of patients with autism, supporting the view that heightened immune response may be an essential factor in the onset of autistic symptoms.[ medical citation needed ] A 2013 review also found evidence of microglial activation and increased cytokine production in postmortem brain samples from people with autism. [40]

Neuropathies

The prevalence of peripheral neuropathies would be significantly increased in autism. [41] Peripheral neuropathies may be asymptomatic. Peripheral neuropathy is a common manifestation of mitochondrial diseases[ medical citation needed ] and polyneuropathies would be relatively common.[ medical citation needed ]

Obsessive–compulsive disorder

Obsessive–compulsive disorder is characterized by recurrent obsessive thoughts or compulsive acts. About 30% of individuals with autism also have OCD.[ medical citation needed ]

Obsessive–compulsive personality disorder

Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder characterized by a general pattern of excessive concern with orderliness, perfectionism, attention to details, mental and interpersonal control and a need for control over one's environment which interferes with personal flexibility, openness to experience and efficiency as well as interfering with relationships.

There are considerable similarities and overlap between autism and OCPD, [42] such as list-making, inflexible adherence to rules and obsessive aspects of routines, though the latter may be distinguished from OCPD especially regarding affective behaviors, bad social skills, difficulties with theory of mind and intense intellectual interests e.g. an ability to recall every aspect of a hobby. [43]

Psychosis and schizophrenia

Childhood-onset schizophrenia is preceded by childhood autism in almost half of cases, and an increasing number of similarities are being discovered between the two conditions. [44] Studies have also found that the presence of psychosis in adulthood is significantly higher in those with autism, especially those with PDD-NOS, than in the general population.[ medical citation needed ] This psychosis generally occurs in an unusual way, with most individuals with autism experiencing a highly atypical collection of symptoms.[ medical citation needed ]

Schizoid personality disorder

Schizoid personality disorder (SPD) is a personality disorder characterized by a lack of interest in social relationships, a tendency towards a solitary or sheltered lifestyle, secretiveness, emotional coldness, detachment and apathy. Other associated features include stilted speech, a lack of deriving enjoyment from most, if not all, activities, feeling as though one is an "observer" rather than a participant in life, an inability to tolerate emotional expectations of others, apparent indifference when praised or criticised, a degree of asexuality and idiosyncratic moral or political beliefs.[ medical citation needed ] Symptoms typically start in late childhood or adolescence.[ medical citation needed ]

Several studies have reported an overlap, confusion or comorbidity with Asperger syndrome (which has been combined with autism and no longer appears as a diagnostic label in the DSM-5). [45] Asperger syndrome was at one time called "schizoid disorder of childhood". Eugen Bleuler coined the term "autism" to describe withdrawal to an internal fantasy, against which any influence from outside becomes an intolerable disturbance. [46]

Although the cause for this comorbidity is not yet certain, genetic evidence for a spectrum between cluster A personality disorders/schizophrenia and autism has been found. [47] [note 1]

Self-injury and suicide

Self-injurious behaviors are relatively common in autistic people, and can include head-banging, self-cutting, self-biting, and hair-pulling. [48] Some of these can result in serious injury or death. [48] Autistic people are about three times as likely as non-autistic people to engage in self-injury. [49]

Theories about the cause of self-injurious behavior in children with developmental delay, including autistic children, include: [50]

Risk factors for self-harm and suicidality include circumstances that could affect anyone, such as mental health problems (e.g., anxiety disorder) and social problems (e.g., unemployment and social isolation), plus factors that affect only autistic people, such as actively trying to behave like a neurotypical person, which is called masking. [51] Approximately 8 in 10 people with autism suffer from a mental health problem in their lifetime, in comparison to 1 in 4 of the general population that suffers from a mental health problem in their lifetimes.[ medical citation needed ]

Rates of suicidality vary significantly depending upon what is being measured. [51] This is partly because questionnaires developed for neurotypical subjects are not always valid for autistic people. [51] As of 2023, the Suicidal Behaviours Questionnaire–Autism Spectrum Conditions (SBQ-ASC) is the only test validated for autistic people. [51] According to some estimates, about a quarter of autistic youth [52] and a third of all autistic people [51] [53] have experienced suicidal ideation at some point. Rates of suicidal ideation are the same for people formally diagnosed with autism and people who have typical intelligence and are believed to have autism but have not been diagnosed. [51]

Although most people who attempt suicide are not autistic, [51] autistic people are about three times as likely as non-autistic people to make a suicide attempt. [49] [54] Less than 10% of autistic youth have attempted suicide, [52] but 15% to 25% autistic adults have. [51] [53] The rates of suicide attempts are the same among people formally diagnosed with autism and those who have typical intelligence and are believed to have autism but have not been diagnosed. [51] The suicide risk is lower among cisgender autistic males and autistic people with intellectual disabilities. [51] [54] The rate of suicide results in a global excess mortality among autistic people equal to approximately 2% of all suicide deaths each year. [54]

Sensory problems

Unusual responses to sensory stimuli are more common and prominent in individuals with autism, and sensory abnormalities are commonly recognized as diagnostic criteria in autism, as reported in the DSM-5; although there is no good evidence that sensory symptoms differentiate autism from other developmental conditions. [55] Sensory processing disorder is comorbid with autism, with comorbidity rates of 42–88%. [56] With or without meeting the standards of SPD, about 90% of autistic individuals have some type of atypical sensory experiences, described as both hyper- and hypo-reactivity. [57] The prevalence of reported "unusual sensory behaviors" that affect functioning in everyday life is also higher, ranging from 45 to 95% depending on factors such as age, IQ and the control group used.[ medical citation needed ]

Several studies have reported associated motor problems that include poor muscle tone, poor motor planning, and toe walking; autism is not associated with severe motor disturbances.[ medical citation needed ]

Sleep disorders

Sleep disorders are commonly reported by parents of individuals with autism, including late sleep onset, early morning awakening, and poor sleep maintenance; [24] sleep disturbances are present in 53–78% of individuals with autism. [58] Unlike general pediatric insomnia, which has its roots in behavior, sleep disorders in individuals with autism are comorbid with other neurobiological, medical, and psychiatric issues. [58]

If not addressed, severe sleep disorders can exacerbate autistic behaviors such as self-injury;[ medical citation needed ] however, there are no Food and Drug Administration-approved pharmacological treatments for pediatric insomnia at this time. [59]

Studies have found abnormalities in the physiology of melatonin and circadian rhythm in people with autism. [60]

Strabismus

According to several studies, there is a high prevalence of strabismus in autistic individuals, with rates 3–10 times that of the general population. [61]

Tourette syndrome

The prevalence of Tourette syndrome among individuals who are autistic is estimated to be 6.5%, higher than the 2% to 3% prevalence for the general population. Several hypotheses for this association have been advanced, including common genetic factors and dopamine, glutamate or serotonin abnormalities. [4]

Tuberous sclerosis

Tuberous sclerosis is a rare genetic disorder that causes benign tumors to grow in the brain as well as in other vital organs. It has a consistently strong association with the autism spectrum. One to four percent of autistic people also have tuberous sclerosis. [62] Studies have reported that between 25% and 61% of individuals with tuberous sclerosis meet the diagnostic criteria for autism with an even higher proportion showing features of a broader pervasive developmental disorder. [63]

Other mental disorders

Phobias and other psychopathological disorders have often been described along with autism but this has not been assessed systematically. [64]

Notes

References

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