Conditions comorbid to autism spectrum disorders

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Autism spectrum disorders (ASD) are developmental disorders that begin in early childhood, persist throughout adulthood, and affect three crucial areas of development: communication, social interaction and restricted patterns of behavior.[1] There are many conditions comorbid to autism spectrum disorders such as fragile X syndrome and epilepsy.

In medicine and in psychiatry, comorbidity is the presence of one or more additional conditions co-occurring with the primary one, or the effect of such additional disorders. About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome,[2] and ASD is associated with several genetic disorders,[3] perhaps due to an overlap in genetic causes.[4]

Distinguishing between ASDs and other diagnoses can be challenging because the traits of ASDs often overlap with symptoms of other disorders and the characteristics of ASDs make traditional diagnostic procedures difficult.[5][6]

Comorbid conditions[edit]

Mitochondrial Diseases[edit]

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). 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, cardiac conduction defects, cardiomyopathy, diabetes, visual and hearing loss, organ failure, neuropathic pain and peripheral neuropathy, ect... The prevalence estimates of mitochondrial disease and dysfunction across studies ranging from about 5 to 80%. This may be, in part, due to the unclear distinction between mitochondrial disease and dysfunction. Mitochondrial diseases are difficult to diagnose and have become better known and diagnosed. Studies indicating the highest rates of mitochondrial diagnosis are usually the most recent. [7]


Anxiety disorders are common among children and adults with ASD. Symptoms are likely affected by age, level of cognitive functioning, degree of social impairment, and ASD-specific difficulties. Many anxiety disorders, such as social anxiety disorder and generalized anxiety disorder, are not commonly diagnosed in people with ASD because such symptoms are better explained by ASD itself, and it is often difficult to tell whether symptoms such as compulsive checking are part of ASD or a co-occurring anxiety problem. The prevalence of anxiety disorders in children with ASD 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.[8]

Attention-deficit hyperactivity disorder[edit]

Previously, the diagnosis manual DSM-IV did not allow the co-diagnosis of ASD and attention-deficit hyperactivity disorder (ADHD). However, following years of clinical research, the most recent publication (DSM-5) in 2013 removed this prohibition of co-morbidity. Thus, individuals with autism spectrum disorder may also have a diagnosis of ADHD, with the modifiers of inattentive, hyperactive, combined-type, or not otherwise specified. 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 spectrum disorder may benefit from additional types of medications.[9][10]

Bipolar disorder[edit]

Bipolar disorder, or manic-depression, is itself often claimed to be comorbid with a number of conditions, including autism.[11] Autism includes some symptoms commonly found in mood and anxiety disorders.[12]

Bowel disease[edit]

Some individuals with autism also have gastrointestinal (GI) symptoms, but there is a lack of published rigorous data to support the theory that children with autism have more or different GI symptoms than usual.[13] It has been claimed that up to fifty percent of children with autism experience persistent gastrointestinal tract problems, ranging from mild to moderate degrees of inflammation in both the upper and lower intestinal tract. This has been described as a syndrome, autistic enterocolitis, by Dr. Andrew Wakefield; this diagnostic terminology has been rejected by medical experts as pseudoscience. His study, which included a total of 12 children, implied that the MMR vaccine causes autism and autistic enterocolitis. The Lancet eventually retracted Wakefield's study. Furthermore, the General Medical Council of the UK subsequently revoked Wakefield's license to practice medicine as a result of the study, citing Wakefield's numerous violations of ethical principles, including failure to disclose financing from lawyers who were preparing a suit against vaccine manufacturers.[14] Constipation, often with overflow, or encopresis, is often associated with developmental disorders in children, and is often difficult to resolve, especially among those with behavioral and communication problems.[15]

Developmental coordination disorder[edit]

The initial accounts of Asperger syndrome[16] and other diagnostic schemes[17] include descriptions of developmental coordination disorder. Children with ASD 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, or problems with visual-motor integration, visual-perceptual skills, and conceptual learning.[16][18] They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder, balance, tandem gait, and finger-thumb apposition.[16]


ASD is also associated with epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder.[19] One in four autistic children develops seizures, often starting either in early childhood or adolescence.[20] 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,[21] and is more common in females and individuals who also have a comorbid intellectual disability.

Fragile X syndrome[edit]

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 affects about two to five percent of people with ASD.[22] If one child has Fragile X, there is a 50% chance that boys born to the same parents will have Fragile X (see Mendelian genetics). Other members of the family who may be contemplating having a child may also wish to be checked for the syndrome.

Gender dysphoria[edit]

Gender dysphoria is a diagnosis given to people (eg transgender) who experience discomfort related to their gender identity.[23] Autistic people are more likely to experience gender dysphoria.[24][25]

Intellectual disability[edit]

The fraction of autistic individuals who also meet criteria for intellectual disability has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing autistic intelligence.[26] For example, a 2001 British study of 26 autistic children found about 30% with intelligence in the normal range (IQ above 70), 50% with a mild to moderate intellectual disability, and about 20% with a severe to profound intellectual disability (IQ below 35). For ASD other than autism the association is much weaker: the same study reported normal intelligence in about 94% of 53 children with PDD-NOS.[27] Estimates are that 40–69% of individuals with ASD have some degree of an intellectual disability,[28] with females more likely to be in severe range of an intellectual disability. Learning disabilities are also highly comorbid in individuals with an ASD. Approximately 25–75% of individuals with an ASD also have some degree of learning disability,[29] 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.[30] It is possible that the association between an intellectual disability and autism is not because they usually have common causes, but because the presence of both makes it more likely that both will be diagnosed.[31]

The CDC states that based on information from 11 reporting states 46% of people with autism have above 85 IQ.[32]

Neuroinflammation and immune disorders[edit]

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.[33] A 2013 review also found evidence of microglial activation and increased cytokine production in postmortem brain samples from people with autism.[34]

Vitamin deficiencies[edit]

Vitamin deficiencies are more common in autism spectrum disorders than in the general population. Vitamin B12 deficiency is one of the most serious. It has been found that special diets that are inadequate for children with ASD usually result in excessive amounts of certain nutrients, but also persistent vitamin deficiencies. [35] [36]

Abnormalities of melatonin and circadian rhythm[edit]

Studies have found abnormalities in the physiology of melatonin and circadian rhythm in people with autism spectrum disorders (ASD). These physiological abnormalities include lower concentrations of melatonin or melatonin metabolites in ASDs compared to controls. [37]

Nonverbal learning disorder[edit]

Obsessive-compulsive disorder[edit]

Obsessive-compulsive disorder is characterized by recurrent obsessive thoughts or compulsive acts. About 30% of individuals with autism spectrum disorders also have OCD.[38]

Tourette syndrome[edit]

The prevalence of Tourette syndrome among individuals with autism 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.[3]

Sensory problems[edit]

Unusual responses to sensory stimuli are more common and prominent in individuals with autism, although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.[39] Sensory processing disorder is comorbid with ASD, with comorbidity rates of 42–88%.[40]

Several studies have reported associated motor problems that include poor muscle tone, poor motor planning, and toe walking; ASD is not associated with severe motor disturbances.[41]

Many with ASD often find it uncomfortable to sit or stand in a way which neurotypical people will find ordinary, and will instead they may appear to be in an awkward position, such as standing with both feet together, supinating, sitting cross-legged or with one foot on top of the other or simply having an awkward gait. However, despite evidently occurring more often in people with ASD, all evidence is anecdotal and unresearched at this point. It has been observed by some psychologists that there is commonality to the way in which these 'awkward' positions may manifest.[42]

Tuberous sclerosis[edit]

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.[43] 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.[44]

Sleep disorders[edit]

Sleep disorders are commonly reported by parents of individuals with ASDs, including late sleep onset, early morning awakening, and poor sleep maintenance;[21] sleep disturbances are present in 53–78% of individuals with ASD.[45] Unlike general pediatric insomnia, which has its roots in behavior, sleep disorders in individuals with ASD are comorbid with other neurobiological, medical, and psychiatric issues.[45]

If not addressed, severe sleep disorders can exacerbate ASD behaviors such as self-injury;[46] however, there are no Food and Drug Administration-approved pharmacological treatments for pediatric insomnia at this time.[47] Some evidence suggests that melatonin supplements improve sleep patterns in children with autism but robust, high-quality studies are overall lacking.[48][49]

Other mental disorders[edit]

Phobias, depression and other psychopathological disorders have often been described along with ASD but this has not been assessed systematically.[50]

The presentation of depression in ASDs can depend on level of cognitive functioning, with lower functioning children displaying more behavior issues and higher functioning children displaying more traditional depressive symptoms.[5] Depression is thought to develop and occur more in high-functioning individuals during adolescence, when they develop greater insight into their differences from others.[28]

See also[edit]


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