Autism Spectrum Disorders

Photo courtesy of Raising Children NetworkOpens in new window Autism spectrum disorders are a group of related neurodevelopmental disorders characterized by a collection of neurobehavioral and neurological dysfunctions, including deficits in social interaction and communication and by abnormalities in behaviors, interests, and activities. The disorders, often occurring before age 36 months, include autismOpens in new window, childhood disintegrative disorder (CDD)Opens in new window, Asperger syndromeOpens in new window, Rett syndromeOpens in new window, and pervasive developmental disorder-not-otherwise specified (PDD-NOS)Opens in new window

There are two major diagnostic classification systems in current use, the International Classification of Diseases, version 10 (ICD-10)Opens in new window and the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)Opens in new window.

ICD-10 was endorsed by the Forty-third World Health AssemblyOpens in new window in May 1990 and came into use in WHO Member StatesOpens in new window beginning in 1994. DSM-IV contains diagnostic criteria used in the United States and many other parts of the world. These diagnostic classification systems have similar symptom criteria for diagnosis of ASD based on three general impairments:

1. severe developmental deficits in socialization
2. delayed or abnormal language and communication both verbal and nonverbal,
3. repetitive or unusual behaviors.

Austistic individuals display behavioral symptoms that include ritualistic features, reliance on routines, and impairment of imaginative play. ASD include autismOpens in new window, Asperger syndromeOpens in new window, childhood disintegrative disorder (CDD)Opens in new window, Rett syndromeOpens in new window, and pervasive developmental disorder-not-otherwise specified (PDD-NOS)Opens in new window. The terms ASD and autism are often used interchangeably.

• Asperger syndromeOpens in new window is characterized by higher intellectual and adequate language abilities; however the deficits in socialization, empathy and human relationships remain.
• Childhood disintegrative disorder (CDD)Opens in new window, also known as Heller’s syndrome, shows normal development, generally up to an age of 2 years, comparable to other children of the same age. However, from around the age of 2 through the age of 10, language and play skills are lost almost completely.
• Rett syndromeOpens in new window also shows normal development up to an age of 2 years; then follows with autistic behavior and developmental delay, with abnormalities of muscle tone, coordination difficulties, loss of ability to walk, writhing limb movements, avoidance of eye contact, and hyperventilation.
  
  Rett syndrome is seen almost always in girls. Rett syndrome is an X-linked ASDOpens in new window caused by mutationsOpens in new window in MECP2 gene, encoding methyl CpG-binding protein 2. The MeCP2 protein likely plays a role in forming connections (synapses) between nerve cells and seems to be critical for normal brain development. Mutations in the CDKL5 gene cause an atypical form of Rett syndrome in females called the early-onset seizure variant.
• PDD-NOSOpens in new window includes individuals who meet some of the criteria for autism or Asperger syndrome, but not all. People with PDD-NOS usually have fewer and milder symptoms than those with autism.

There has been an alarming 556% increase in the prevalence of ASD reported between 1991 and 1997, a prevalence higher than that of spina bifidaOpens in new window, cancer, or Down syndromeOpens in new window.

The Centers for Disease Control and Prevention (CDC)Opens in new window reported that between 4.2 to 12.1 per 1,000 children with an average of 9.0 per 1,000 children were identified with an ASD in the USA. This translates to about 1 in 80 and 1 in 240 children with an average of about 1 in 110 identified with an ASD.

There were ten communities who participated in an earlier 2002 surveillance year and the newer 2006 surveillance year. These communities observed an increase in identified ASD prevalence, ranging from 27% to 95% with an average increase of 57%. Identified ASD prevalence increased across all sex, racial, ethnic and cognitive functioning subgroups. For all sites, the most consistent pattern was the increase among boys. ASD prevalence was four to five times higher for boys than for girls with 1 in 70 boys and 1 in 315 girls identified, on average, with one of the ASD syndromes.

The prevalence of parent-reported diagnosis of ASD among US children aged 3 to 17 years was estimated from the 2007 National Survey of Children’s Health (sample size: 78037); a study that was nation-wide and included all US regions. It was based on parental reports during a phone survey with no corroboration of the diagnoses. The weighted current ASD point-prevalence was 110 per 10,000. This group of authors estimated that 673,000 US children have ASD. Odds of having ASD were 4 times as large for boys than girls.

Non-Hispanic (NH) black and multiracial children had lower odds of ASD than NH white children. This observed point-prevalence, 1 in 91, is higher than previous US estimates. More inclusive survey questions, increased population awareness, and improved screening and identification by providers may partly explain this finding.

Diagnostic Process of ASD

The abnormal behavior can be seen in some children early, usually within a few months of life. However, the diagnostic process requires detailed and repeated clinical examination of anamnestic data, including exploration of the patient’s and family’s history.

A comprehensive evaluation requires a thorough review that may include looking at the child’s behavior and development and interviewing the parents. Psychotic disturbances, autism occurrence and mental retardation within the family, depressive and bipolar disorders, suicide and suicidal attempts are examined in familiar anamnesis.

In the personal history, we explore problems of social and communicative skills, receptive and expressive vocabulary, other language skills, and use of non-verbal communicative skills. We evaluate:

• social communication
• eye contact
• structure of interests
• imitative skills
• interactive strategies
• the pattern of behavior
• stereotypes
• resistance to change
• unusual interests
• idiosyncrasy to environment conditions
• play and its peculiarities
• material preferences
• structure of eating behavior
• symptoms of hyperactivity
• impulsivity
• aggressiveness
• symptoms of mood disturbances
• relationships with socially important relation, and
• adaptation to the social environment; namely to school.

Psychopathological symptoms include:

• altered activity
• psychokinetic attenuation
• hyperkinesis
• existence of psychomotor agitation
• movement stereotypia
• verbigeration
• echolalia
• echopraxis
• echomimic
• automatic expressions of styling behavior
• mannerisms, and
• flapping movements.

We attempt to notice all unusual and bizarre behavior; parakinetic expressions in mimics, regressive parakinesis, things that represent ontogenic and phylogenetically older patterns of behavior.

Pediatric examination, genetic testing, neurological testing with the use of selected imaging methods (CT and MRI) and EEG, hearing and vision screening, belongs in a detailed diagnosis. Psychological examination with complex intellect evaluation is important. Psychiatric and psychological examination can be completed with scale tests (CAR, ADIR). The final assessment and diagnosis thus requires the cooperation of psychiatrists, pediatricians, child neurologists, and child psychologists.

AutismOpens in new window is currently detected only at about three years of age. However, some deficits and disturbances connected with ASD are possible to observe at 12-18 months of age.

Healthy toddlers develop dyadic interaction with caregivers (mostly with parents) at 3-4 months, even earlier.

Baron-Cohen and co-workers screened 41 18-month-old toddlers who were at high genetic risk for developing autism, and 50 randomly selected 18-month-olds, using a new instrument, the CHAT (Checklist for Autism in Toddlers)Opens in new window.

More than 80% of the randomly selected 18-month-old toddlers passed on all items. Four children in the high-risk group failed on two or more of five key types of behavior:

1. pretend play
2. protodeclarative pointing
3. joint-attention
4. social interest, and
5. social play.

These four toddlers received a diagnosis of autism by 30 months.

Ostering and Dawson analyzed video records of play of one-year old infants. Eleven children, which were later diagnosed as autistics, were delayed in social behavior and shared attention.

These infants had a lack of interest for objects, face of other persons, and reaction to its own name. IQ of these infants was not different from control healthy infants. Recently, the Modified Checklist for Autism in Toddlers (M-CHAT)Opens in new window is widely used to screen toddlers with ASD risk.

Pharmacotherapy of ASD

Pharmacotherapy of autism is often targeted to some dominant symptoms and/or symptoms of comorbid disorders, such as psychomotor instability and aggressiveness, hyperactivity and behavioral disorders, repetitive rituals and motor mannerisms, and sleeping disorders.

HaloperidolOpens in new window and risperidoneOpens in new window were used in control studies of psychomotor instability and aggressiveness. Forty autistic children (2 – 7 years) were treated with haloperidol (1.7 mg/day) for eight weeks. Some 69% of the children were improved; adverse effects appeared as acute dystoniaOpens in new window and dyskinesiaOpens in new window, which subsided with drug withdrawal.

Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with ASD. Risperidone was used for treatment in two double-blind placebo control studies, altogether in 1180 children; doses were approximately 1.8 mg/day and therapy was successful in 70 – 87%.

McDougle and co-workers treated 101 autistic children at the age 5 – 17 years with risperidone in an 8-week double-blind, placebo-controlled trial and 63 autistic children in a 16-week open-lable continuation study.

Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication.

Research Units on the Pediatric Psychopharmacology Autism Network (RUPP) studied in 2005 75 children treated with methylfenidate (younger than 11 years of age) in double-blind control study (0. 125 – 0.54 mg/kg three times a day). Methylfenidate was better than placebo in 50% of the children and side effects were prominent in 18% of patients (especially irritability).

Hollander with co-workers examined the selective serotonin reuptake inhibitor fluoxetine in the treatment of repetitive behaviors in children and adolescents with ASD. In total, 45 child or adolescent patients with ASD were randomized into two acute, 8-week phases in a double-blind placebo-controlled crossover study of liquid fluoxetine (2.5 – 9.9 mg/day). Fluoxetine in low doses was more effective than placebo in the treatment ofrepetitive behaviors in childhood autism.

Buchsbaum et al. measured the effect of fluoxetine on regional cerebral metabolism in ASD. Autism scores showed three of the patients had much improved and three were unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulated gyrus and the orbitofrontal cortex.

Sleep disorders of autistic patients are treated by melatoninOpens in new window. In a retrospective study, 107 children (2 – 18 years of age) with a confirmed diagnosis of ASD received melatonin (0.5 – 3 mg/day).

Parents of 64 children (60%) reported improved sleep, although they continued to have concerns regarding sleep. Parents of 14 children (13%) continued to report sleep problems as a major concern, with only one child having worse sleep after starting melatonin (1%), and one child having undetermined response (1%).

Only three children had mild side effects after starting melatonin, which included morning sleepiness and increased enuresis. There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures. The majority of children were taking psychotropic medications.

Some other targeted pharmacotherapeutic approaches have been investigated, such as the application of α-adrenergic agonists, atypical neuroleptics, such as aripiprazol and olanzapin.

AripiprazoleOpens in new window was tested in double blind control-study in doses 5, 10, and 15mg/day for 8-week in patients with ASD. Aripiprazole was more effective than placebo and the diverse effects were sedation, tremor, and akathisia. Interesting are preliminary studies with intranasal oxytocin application, but this treatment requires further studies.

Promising treatments include melatonin, antioxidants, acetylcholinesterase inhibitors, and naltrexone. All of the reviewed treatments are currently considered off-label for ASD (i.e., not FDA-approved) and some have adverse effects.

Further studies exploring these treatments are needed. Research and practical experience has shown that the most effective treatment of ASD is a combination of specialized and supportive educational programming, communication training (such as speech/language therapy), social skills support and behavioral intervention. Children with autism benefit from intensive, early intervention that focuses on increasing the frequency, form, and function of communicative acts.