Conditions comorbid to autism spectrum disorders
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Autism spectrum disorder The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder, neurodevelopmental condition (or conditions) ...
(ASD) is a
developmental disorder Developmental disorders comprise a group of psychiatric conditions originating in childhood that involve serious impairment in different areas. There are several ways of using this term. The most narrow concept is used in the category "Specific Di ...
that begins in early childhood, persists throughout adulthood, and affects three crucial areas of development: communication, social interaction and restricted patterns of behavior. There are many conditions comorbid to autism spectrum disorder such as
fragile X syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may ...
and
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
. In medicine and in psychiatry,
comorbidity In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often wikt:co-occur#Verb, co-occurring (that is, wikt:concomitant#Adjecti ...
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 Mendelian inheritance (also known as Mendelism) is a type of biology, biological Heredity, inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, an ...
(single-gene) condition,
chromosome abnormality A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
, or other genetic syndrome, and ASD is associated with several
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s, perhaps due to an overlap in genetic causes. 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.


Comorbid conditions


Anxiety

Anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
s 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 Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impaired ability to function in at least some aspects ...
and
generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...
, 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. A
systematic review A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
summarized available evidence on interventions to reduce anxiety in school children with autism spectrum disorder. Of the 24 studies reviewed, 22 used a
cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
(CBT) approach. The review found that CBT was moderately to highly effective at reducing anxiety in school children with autism spectrum disorder, 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.


Brain fog

Brain fog is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long-term memory. Brain fog can be present in patients with autism spectrum disorder (ASD). Its prevalence, however, remains unknown.


Bipolar disorder

Bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
, or manic-depression, is itself often claimed to be comorbid with a number of conditions, including autism. Autism includes some symptoms commonly found in mood and anxiety disorders.


Bowel disease

Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. The most common gastrointestinal symptoms reported by proprietary tool developed and administered by Mayer, Padua, & Tillisch (2014) are abdominal pain, constipation, diarrhea and bloating, reported in at least 25 percent of participants. Carbohydrate digestion and transport is impaired in individuals with autism spectrum disorder, 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. Altered gastrointestinal function accompanied by pain may induce feeding issues and increase perceived negative behaviors, including self injury, in individuals with autism.


Depression

Major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
has been shown by several studies to be one of the most common comorbid conditions in those with ASD, 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. In addition, the presentation of depression in ASDs 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.


Developmental coordination disorder

The initial accounts of
Asperger syndrome Asperger syndrome (AS), also known as Asperger's, is a former neurodevelopmental disorder characterized by significant difficulties in Interpersonal relationship, social interaction and nonverbal communication, along with restricted and re ...
and other diagnostic schemes include descriptions of
developmental coordination disorder Developmental coordination disorder (DCD), also known as developmental motor coordination disorder, developmental dyspraxia or simply dyspraxia from the word 'praxis' meaning to do or act, is a neurodevelopmental disorder characterized by impair ...
. 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, other hand/dexterity impairments, or problems with visual-motor integration, visual-perceptual skills, and conceptual learning. They may show problems with
proprioception Proprioception ( ), also referred to as kinaesthesia (or kinesthesia), is the sense of self-movement, force, and body position. It is sometimes described as the "sixth sense". Proprioception is mediated by proprioceptors, mechanosensory neurons ...
(sensation of body position) on measures of
developmental coordination disorder Developmental coordination disorder (DCD), also known as developmental motor coordination disorder, developmental dyspraxia or simply dyspraxia from the word 'praxis' meaning to do or act, is a neurodevelopmental disorder characterized by impair ...
, balance,
tandem gait Tandem gait is a gait (method of walking or running) where the toes of the first foot touch the heel of the next one at each step. Neurologists sometimes ask patients to walk in a straight line using tandem gait as a test to help diagnose ataxia, es ...
, and finger-thumb apposition.


Epilepsy

ASD is also associated with
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder. One in four autistic children develops
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, often starting either in early childhood or adolescence. 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 Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
can help confirm the seizure's presence. Typically, onset of epilepsy occurs before age five or during puberty, and is more common in females and individuals who also have a comorbid
intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...
.


Fragile X syndrome

Fragile X syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may ...
is the most common inherited form of
intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...
. 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. 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 Mendelian inheritance (also known as Mendelism) is a type of biology, biological Heredity, inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, an ...
). Other members of the family who may be contemplating having a child may also wish to be checked for the syndrome.


Gender dysphoria

Gender dysphoria Gender dysphoria (GD) is the distress a person experiences due to a mismatch between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The diagnostic label gender identity disorder (GID) was used until ...
is a diagnosis given to
transgender A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through tr ...
people who experience discomfort related to their gender identity. Autistic people are more likely to experience gender dysphoria. Around 20% of gender identity clinic-assessed individuals reported characteristics of ASD.


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.


Abnormal folate metabolism

Several lines of evidence indicate abnormalities of folate metabolism in ASD. These abnormalities can lead to a decrease in 5-methyltetrahydrofolate production, alter the production of folate metabolites and reduce folate transport across the blood-brain barrier and in neurons. The most significant abnormalities of folate metabolism associated with ASDs may be autoantibodies to the alpha folate receptor (FRα). These autoantibodies have been associated with
cerebral folate deficiency Cerebral folate deficiency is a condition in which concentrations of 5-methyltetrahydrofolate are low in the brain as measured in the cerebral spinal fluid despite being normal in the blood. Symptoms typically appear at about 5 to 24 months of age ...
. Autoantibodies can bind to FRα and greatly impair its function. In 2013, one study reported that 60% and 44% of 93 children with ASD were positive for FRα-blocking and binding autoantibodies, respectively. This high rate of anti-FRα autoantibody positivity was confirmed by Ramaekers et al. who compared 75 children with ASD to 30 non-autistic "controls". These controls were children who had a developmental delay, but did not have ASD. FRα-blocking autoantibodies were positive in 47% of children with ASD, but only in 3% of children without ASD. Many children with ASD and
cerebral folate deficiency Cerebral folate deficiency is a condition in which concentrations of 5-methyltetrahydrofolate are low in the brain as measured in the cerebral spinal fluid despite being normal in the blood. Symptoms typically appear at about 5 to 24 months of age ...
have marked improvements in their clinical status when taking folinic acid. A series of five children with
cerebral folate deficiency Cerebral folate deficiency is a condition in which concentrations of 5-methyltetrahydrofolate are low in the brain as measured in the cerebral spinal fluid despite being normal in the blood. Symptoms typically appear at about 5 to 24 months of age ...
and low functioning autism with neurological deficits found a complete reduction of ASD symptoms with the use of folinic acid in a child and substantial improvements in communication in two other children.


Abnormal redox metabolism

An imbalance in glutathione-dependent redox metabolism has been shown to be associated with autism spectrum disorders (ASD). Glutathione synthesis and intracellular redox balance are related to folate metabolism and methylation, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct endophenotype of TSA closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Glutathione is involved in neuroprotection against oxidative stress and neuroinflammation by improving the antioxidant stress system. In autistic children, studies have shown that glutathione metabolism can be improved. - Subcutaneously by injection of methylcobalamin. - Oral folinic acid. - A vitamin and mineral supplement that includes antioxidants, coenzyme Q10 and vitamins B. - Tetrahydrobiopterin. Interestingly, recent DBPC studies have shown that N-acetyl-1-cysteine, a glutathione precursor supplement, is effective in improving the symptoms and behaviors associated with ASD. However, glutathione was not measured in these studies. Small, medium and large DPBC trials and open small and medium-sized clinical trials demonstrate that new treatments for children with ASD for oxidative stress are associated with improvements in baseline symptoms of ASD, sleep, gastrointestinal symptoms, hyperactivity, seizures and parental impression, sensory and motor symptoms. These new treatments include N-acetyl-l-cysteine, methylcobalamin with and without oral folinic acid, vitamin C, and a vitamin and mineral supplement that includes antioxidants, enzyme Q10, and B vitamins. Several other treatments that have antioxidant properties, including carnosine, have also been reported to significantly improve ASD behaviors, suggesting that treatment of oxidative stress could be beneficial for children with ASD. Many antioxidants can also help improve mitochondrial function, suggesting that clinical improvements with antioxidants could occur through a reduction in oxidative stress and / or an improvement in mitochondrial function. Some of these treatments can have frequent serious side effects (
bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...
, etc. ...).


Neurotransmitter anomalies


Mitochondrial diseases

The central player in bioenergetics is the
mitochondrion A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
. 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 disease Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of ...
s 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 Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
,
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, cognitive regression,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...
s, cardiopathies (cardiac conduction defects,
hypertensive heart disease Hypertensive heart disease includes a number of complications of high blood pressure that affect the heart. While there are several definitions of hypertensive heart disease in the medical literature, the term is most widely used in the context of ...
,
cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, etc...),
diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
visual The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (the ...
and
hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...
,
organ failure Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention. It is not a diagnosi ...
,
neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
and
peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
. 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 detected. Studies indicating the highest rates of mitochondrial diagnosis are usually the most recent. Some drugs are toxic to mitochondria. These can trigger or aggravate dysfunctions or mitochondrial diseases. * Antiepileptics : Valproic acid (also used in various other indications) and phenytoin are the most toxic. Phenobarbital, carbamazepine, oxcarbazepine, ethosuximide, zonisamide, topiramate, gabapentin and vigabatrin are also. * Other types of drugs : Corticosteroids (such as cortisone), isotretinoin (Accutane) and other vitamin A derivatives, barbiturates, certain antibiotics, propofol, volatile anesthetics, non-depolarizing muscle relaxants, some local anesthetics, statins, fibrates, glitazones, beta blockers, biguanides, amiodarone, some chemotherapies, some neuroleptics, nucleoside reverse transcriptase inhibitors and various other drugs.


Neurofibromatosis type I

ASD is also associated with Neurofibromatosis type I (NF-1). NF-1 is a complex multi-system human disorder caused by the mutation of a gene on
chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...
that is responsible for production of a protein, called
neurofibromin 1 Neurofibromin 1 (''NF1'') is a gene in humans that is located on chromosome 17. ''NF1'' codes for neurofibromin, a GTPase-activating protein that negatively regulates RAS/MAPK pathway activity by accelerating the hydrolysis of Ras-bound GTP. ''N ...
, 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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(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 Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
of patients with autism, supporting the view that heightened immune response may be an essential factor in the onset of autistic symptoms. A 2013 review also found evidence of microglial activation and increased
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production in postmortem brain samples from people with autism.


Neuropathies

The prevalence of
peripheral neuropathies Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
would be significantly increased in ASD. Peripheral neuropathies may be asymptomatic. Peripheral neuropathy is a common manifestation of mitochondrial diseases and
polyneuropathies Polyneuropathy (wikt:poly-, poly- + wikt:neuro-, neuro- + wikt:-pathy, -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning ...
would be relatively common.
Neuropathies Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
could also be caused by other features of ASD.


Nonverbal learning disorder


Obsessive–compulsive disorder

Obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and/or feels the need to perform certain routines repeatedly to the extent where it induces distress or impairs general ...
is characterized by recurrent obsessive thoughts or compulsive acts. About 30% of individuals with autism spectrum disorders also have OCD.


Obsessive–compulsive personality disorder

Obsessive–compulsive personality disorder Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder marked by an excessive need for orderliness and neatness. Symptoms are usually present by the time a person reaches adulthood, and are visible in a variety o ...
(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 Control may refer to: Basic meanings Economics and business * Control (management), an element of management * Control, an element of management accounting * Comptroller (or controller), a senior financial officer in an organization * Controllin ...
and a need for control over one's environment which interferes with personal
flexibility Stiffness is the extent to which an object resists deformation in response to an applied force. The complementary concept is flexibility or pliability: the more flexible an object is, the less stiff it is. Calculations The stiffness, k, of a bo ...
,
openness to experience Openness to experience is one of the domains which are used to describe human personality in the Five Factor Model. Openness involves six facets, or dimensions: active imagination (fantasy), aesthetic sensitivity, attentiveness to inner feelings, ...
and
efficiency Efficiency is the often measurable ability to avoid wasting materials, energy, efforts, money, and time in doing something or in producing a desired result. In a more general sense, it is the ability to do things well, successfully, and without ...
as well as interfering with relationships. There are considerable similarities and overlap between
Autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
and OCPD, such as list-making, inflexible adherence to rules and obsessive aspects of routines, though the latter may be distinguished from OCPD especially regarding
affective Affect, in psychology, refers to the underlying experience of feeling, emotion or mood. History The modern conception of affect developed in the 19th century with Wilhelm Wundt. The word comes from the German ''Gefühl'', meaning "feeling." ...
behaviors, bad social skills, difficulties with
theory of mind In psychology, theory of mind refers to the capacity to understand other people by ascribing mental states to them (that is, surmising what is happening in their mind). This includes the knowledge that others' mental states may be different fro ...
and intense intellectual interests e.g. an ability to recall every aspect of a hobby. A 2009 study involving adult
autistic The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
people found that 40% of those diagnosed with Autism met the diagnostic requirements for a
co-morbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary c ...
OCPD diagnosis.


Psychosis and schizophrenia

Childhood-onset schizophrenia is preceded by childhood autistic spectrum disorders in almost half of cases, and an increasing number of similarities are being discovered between the two disorders. Studies have also found that the presence of
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
in adulthood is significantly higher in those with autism spectrum disorders, especially those with
PDD-NOS A pervasive developmental disorder not otherwise specified (Including atypical autism) (PDD-NOS) is one of four disorders which were collapsed into the diagnosis of autism spectrum disorder in the DSM-5 and also was one of the five disorders clas ...
, than in the general population. This psychosis generally occurs in an unusual way, with most individuals with ASD experiencing a highly atypical collection of symptoms. Recent studies have also found that the core ASD symptoms also generally present in a slightly different way during the childhood of the individuals that will later become psychotic, long before the actual psychosis develops.


Schizoid personality disorder

Schizoid personality disorder Schizoid personality disorder (, often abbreviated as SzPD or ScPD) is a personality disorder characterized by a Asociality, lack of interest in social relationships, a tendency toward a solitary or sheltered lifestyle, secretiveness, emotion ...
(SPD) is a
personality disorder Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's culture ...
characterized by a lack of interest in social relationships, a tendency towards a solitary or sheltered lifestyle, secretiveness, emotional coldness, detachment and
apathy Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of intere ...
. Other associated features include
stilted speech In psychiatry, stilted speech or pedantic speech is communication characterized by situationally-inappropriate formality. This formality can be expressed both through abnormal prosody as well as speech content that is "inappropriately pompous, leg ...
, 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 Asexuality is the lack of sexual attraction to others, or low or absent interest in or desire for sexual activity. It may be considered a sexual orientation or the lack thereof. It may also be categorized more widely, to include a broad sp ...
and idiosyncratic moral or political beliefs. Symptoms typically start in late childhood or adolescence. Several studies have reported an overlap, confusion or comorbidity with the
autism spectrum disorder The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder, neurodevelopmental condition (or conditions) ...
Asperger syndrome Asperger syndrome (AS), also known as Asperger's, is a former neurodevelopmental disorder characterized by significant difficulties in Interpersonal relationship, social interaction and nonverbal communication, along with restricted and re ...
. Asperger syndrome had traditionally been called "
schizoid disorder of childhood Asperger syndrome (AS), also known as Asperger's, is a former neurodevelopmental disorder characterized by significant difficulties in social interaction and nonverbal communication, along with restricted and repetitive patterns of behav ...
", and
Eugen Bleuler Paul Eugen Bleuler (; ; 30 April 1857 – 15 July 1939) was a Swiss psychiatrist and humanist most notable for his contributions to the understanding of mental illness. He coined several psychiatric terms including "schizophrenia", "schizoid", " ...
coined both the terms "autism" and "schizoid" to describe withdrawal to an internal fantasy, against which any influence from outside becomes an intolerable disturbance. In a 2012 study of a sample of 54 young adults with Asperger syndrome, it was found that 26% of them also met criteria for SPD, the highest comorbidity out of any personality disorder in the sample (the other comorbidities were 19% for
obsessive–compulsive personality disorder Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder marked by an excessive need for orderliness and neatness. Symptoms are usually present by the time a person reaches adulthood, and are visible in a variety o ...
, 13% for
avoidant personality disorder Avoidant personality disorder (AvPD) is a Cluster C personality disorder characterized by excessive social anxiety and inhibition, fear of intimacy (despite an intense desire for it), severe feelings of inadequacy and inferiority, and an overrelia ...
and one female with
schizotypal personality disorder Schizotypal personality disorder (STPD or SPD), also known as schizotypal disorder, is a mental and behavioral disorder. DSM classification describes the disorder specifically as a personality disorder characterized by thought disorder, parano ...
). Additionally, twice as many men with Asperger syndrome met criteria for SPD than women. While 41% of the whole sample were unemployed with no occupation, this rose to 62% for the Asperger's and SPD comorbid group. Although the cause for this comorbidity is not yet certain, genetic evidence for a spectrum between
cluster A personality disorders Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's culture ...
/
schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
and autism spectrum disorders has been found.See
Imprinted brain hypothesis The imprinted brain hypothesis is an unsubstantiated hypothesis in evolutionary psychology regarding the causes of autism spectrum and schizophrenia spectrum disorders, first presented by Bernard Crespi and Christopher Badcock in 2008. It claims ...
,
Causes of schizophrenia Risk factors of schizophrenia include many genetic and environmental phenomena. The prevailing model of schizophrenia is that of a special neurodevelopmental disorder with no precise boundary or single cause (i.e. arises from multiple mechanisms). ...
,
DUF1220 The Olduvai domain, known until 2018 as DUF1220 (domain of unknown function 1220) and the NBPF repeat, is a protein domain that shows a striking human lineage-specific (HLS) increase in copy number and appears to be involved in human brain evolu ...
Tantam suggested that Asperger syndrome may confer an increased risk of developing SPD. In the same 2012 study, it was noted that the
DSM DSM or dsm may refer to: Science and technology * Deep space maneuver * Design structure matrix or dependency structure matrix, a representation of a system or project * Diagnostic and Statistical Manual of Mental Disorders ** DSM-5, the fifth ed ...
may complicate diagnosis of SPD by requiring the exclusion of a
pervasive developmental disorder The diagnostic category pervasive developmental disorders (PDD), as opposed to specific developmental disorders (SDD), is a group of disorders characterized by delays in the development of multiple basic functions including socialization and co ...
(PDD) before establishing a diagnosis of SPD. The study found that social interaction, stereotyped behaviours and specific interests were more severe in the individuals with Asperger syndrome also fulfilling SPD criteria, against the notion that social interaction skills are unimpaired in SPD. The authors believe that substantial subgroup of people with autism spectrum disorder or PDD have clear "schizoid traits" and correspond largely to the "loners" in Lorna Wing's classification ''The autism spectrum'' ( Lancet 1997), described by
Sula Wolff Sulammith (Sula) Wolff FRCP FRCPysch (1 March 1924 – 21 September 2009) was a prominent and pioneering British child psychiatrist. She was amongst the first in her field to identify and define the characteristics of children on the autisti ...
.


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 spectrum disorder (ASD), as reported in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V); although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.
Sensory processing disorder Sensory processing disorder (SPD, formerly known as sensory integration dysfunction) is a condition in which multisensory input is not adequately processed in order to provide appropriate responses to the demands of the environment. Sensory proces ...
is comorbid with ASD, with comorbidity rates of 42–88%. With or without meeting the standards of SPD; about 90% of ASD individuals have some type of atypical sensory experiences, described as both hyper- and hypo-reactivity. The prevalence of reported "unusual sensory ''behaviors"'' that effect functioning in everyday life is also higher; ranging from 45 to 95% depending on factors such as age, IQ and the control group used. Several studies have reported associated motor problems that include
poor muscle tone Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases ...
, poor motor planning, and
toe walking Toe walking refers to a condition where a person walks on their toes without putting much or any weight on the heel or any other part of the foot. This term also includes the inability to connect one's foot fully to the ground while in the stand ...
; ASD is not associated with severe motor disturbances. Many with ASD often find it uncomfortable to sit or stand in a way which neurotypical people will find ordinary, and may stand in an awkward position, such as 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.


Reduced NMDA‐receptor function

Reduced NMDA receptor function has been linked to reduced social interactions, locomotor hyperactivity, self-injury, pre-impulse inhibition (PPI) deficits, and sensory hypersensitivity, among others. Results suggest that NMDA dysregulation could contribute to core ASD symptoms.


Sleep disorders

Sleep disorders are commonly reported by parents of individuals with ASDs, including late sleep onset, early morning awakening, and poor sleep maintenance; sleep disturbances are present in 53–78% of individuals with ASD. Unlike general pediatric
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, which has its roots in behavior, sleep disorders in individuals with ASD are comorbid with other neurobiological, medical, and psychiatric issues. If not addressed, severe sleep disorders can exacerbate ASD behaviors such as
self-injury Self-harm is intentional behavior that is considered harmful to oneself. This is most commonly regarded as direct injury of one's own skin tissues usually without a suicidal intention. Other terms such as cutting, self-injury and self-mutilatio ...
; however, there are no
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
-approved pharmacological treatments for pediatric insomnia at this time. 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. Some evidence suggests that
melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
supplements improve sleep patterns in children with autism but robust, high-quality studies are overall lacking.


Tinnitus

According to one study, 35% of people who are autistic would be affected by
tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...
, which is much higher than in the general population.


Tourette syndrome

The prevalence of
Tourette syndrome Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
,
glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
or
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
abnormalities.


Tuberous sclerosis

Tuberous sclerosis Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...
is a rare genetic disorder that causes benign
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s 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. 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 The diagnostic category pervasive developmental disorders (PDD), as opposed to specific developmental disorders (SDD), is a group of disorders characterized by delays in the development of multiple basic functions including socialization and co ...
.


Vitamin deficiencies

Vitamin deficiencies are more common in autism spectrum disorders than in the general population. * ''Vitamin D'' : Vitamin D deficiency was concerned in a German study 78% of hospitalized autistic population. 52% of the entire ASD group in the study was severely deficient, which is much higher than in the general population. Other studies also show a higher rate of vitamin D deficiencies in ASDs. * ''Vitamine B12'' : The researchers found that, overall, B12 levels in the brain tissue of autistic children were three times lower than those of the brain tissue of children not affected by ASD. This lower-than-normal B12 profile persisted throughout life in the brain tissues of patients with autism. These deficiencies are not visible by conventional blood sampling. As for the classic deficiency of vitamin B12, it would affect up to 40% of the population, its prevalence has not yet been studied in autism spectrum disorders. Vitamin B12 deficiency is one of the most serious. * ''Vitamin B9'' (folic acid) : Studies have been conducted regarding folic acid supplementation in autism in children. "The results showed that folic acid supplementation significantly improved certain symptoms of autism such as sociability, verbal / preverbal cognitive language, receptive language, and emotional expression and communication. In addition, this treatment improved the concentrations of folic acid, homocysteine and redox metabolism of standardized glutathione. " * ''Vitamin A'' : Vitamin A can induce mitochondrial dysfunction. According to a non-specific study on ASD: "Vitamin A and its derivatives, retinoids, are micronutrients necessary for the human diet in order to maintain several cellular functions of human development in adulthood as well as during aging (...) Although it is either an essential micronutrient, used in clinical applications, vitamin A has several toxic effects on the redox environment and mitochondrial function. A decline in the quality of life and an increase in the mortality rate among users of vitamin A supplements have been reported. Although the exact mechanism by which vitamin A causes its deleterious effects is not yet clear (...) Vitamin A and its derivatives, retinoids , disrupt mitochondrial function by a mechanism that is not fully understood." * ''Zinc'' : Zinc deficiency incidence rates in children aged 0 to 3, 4 to 9 and 10 to 15 years were estimated at 43.5%, 28.1% and 3.3% for boys and at 52.5%, 28.7% and 3.5% among girls. * ''Magnesium'' : Incidence rates of magnesium deficiency in children aged 0 to 3, 4 to 9 and 10 to 15 years were estimated at 27%, 17.1% and 4.2% for boys and at 22.9%, 12.7% and 4.3% among girls. * ''Calcium'' : Incidence rates of calcium deficiency in children aged 0 to 3, 4 to 9 years and 10 to 15 years were estimated at 10.4%, 6.1% and 0.4% for boys and at 3.4%, 1.7% and 0.9% among girls. It has been found that special diets that are inappropriate for children with ASD usually result in excessive amounts of certain nutrients and persistent vitamin deficiencies.


Other mental disorders

Phobia A phobia is an anxiety disorder defined by a persistent and excessive fear of an object or situation. Phobias typically result in a rapid onset of fear and are usually present for more than six months. Those affected go to great lengths to avo ...
s and other
psychopathological Psychopathology is the study of Abnormal psychology, abnormal cognition, behaviour, and experiences which differs according to social norms and rests upon a number of constructs that are deemed to be the social norm at any particular era. Biol ...
disorders have often been described along with ASD but this has not been assessed systematically.


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 austistic indificiuals. 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 typical levels of intelligence in about 94% of 53 children with
PDD-NOS A pervasive developmental disorder not otherwise specified (Including atypical autism) (PDD-NOS) is one of four disorders which were collapsed into the diagnosis of autism spectrum disorder in the DSM-5 and also was one of the five disorders clas ...
. Estimates are that 40–69% of individuals with ASD have some degree of an intellectual disability, with females more likely to be in severe range of an intellectual disability.
Learning disabilities Learning disability, learning disorder, or learning difficulty (British English) is a condition in the brain that causes difficulties comprehending or processing information and can be caused by several different factors. Given the "difficult ...
are also highly comorbid in individuals with an ASD. Approximately 25–75% of individuals with an ASD also have some degree of learning disability, 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. 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. The CDC states that based on information from 11 reporting states 46% of people with autism have above 85 IQ.


Attention-deficit hyperactivity disorder

Previously, the diagnosis manual
DSM-IV The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM; latest edition: DSM-5-TR, published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a common langua ...
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 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the ''Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatric ...
) 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.DSM 5 ADHD Fact Sheet


See also

*
Autism and working memory Autism is a neurodevelopmental disorder diagnosed as impaired social interaction and communication, and by restricted and repetitive behavior. In this article, the word ''autism'' is used for referring to the whole range of conditions on the ...


Notes


References

{{Pervasive developmental disorders Autism