AUTISM SPECTRUM DISORDER DSM-V Criteria • Criterion A: Persistent deficits in social communication and interaction • Can include social-emotional reciprocity, nonverbal communicative behaviors, developing/maintaining relationships • Criterion B: Restricted, repetitive patterns of behavior • Repetitive motor movements (rocking), ecolalia, insistence on sameness and a routine, highly restricted, fixated interests, unusual interest in sensory aspects of the environment • Symptoms must be present in early developmental period and cannot be better explained by intellectual disability or global developmental disability • 3 levels of severity • Viewed as a dimensional disorder • Specifiers for each criterion Secondary Features • Intellectual disability • Often large discrepancies in abilities in high functioning kids • Motor disabilities • Odd gait, clumsiness, walking on tiptoes • Self-injury • Inattention • Disruptive behavior • Catatonia • Possible, not particularly common • Most likely during adolescent years Controversy • DSM-IV included categories for Autism, Pervasive Development Disorder NOS, High Functioning Autism, and Asperger’s Syndrome • Sevin et al (1995) studied 34 kids with autism and PDDNOS. Did not find discrete categories. • Categories were collapsed into Autism Spectrum – PDDNOS, HFA, and AS now “on the spectrum” • Concern about retaining diagnoses, receiving services, stigma Controversy • Intent was NOT to remove anyone’s diagnosis • Will actually help some higher functioning kids get services • Everyone should convert to Autism Spectrum with specifications if criteria used correctly • DSM-IV included category for communication difficulty • This is covered by DSM-V criteria A and B. Separate category was not needed DSM-V Schematic Genetics • Unknown Core Symptoms • Social Deficits • Restricted, repetitive behaviors Biological Substrate Secondary Symptoms • Unknown • • • • Intellectual, motor disabilities Self-injury Inattention/Disruptive Behavior Catatonia Assessment – ADI-R • Gold Standards are Autism Diagnostic Interview – Revised (ADI-R) and Autism Diagnostic Observation Scale (ADOS) • ADI-R is semi-structured interview for caregivers • 93 items, about 2 hours • Based on DSM-IV criteria (Communication difficulties, social reciprocity, restricted, repetitive behaviors) • Chakrabarti and Fombonne (2001) found that interrater reliability was excellent on those subscales Assessment - ADOS • Observational • Can be used in nonverbal 2-year-olds – verbal adults and all between • 4 Modules: • Pre-Verbal-Single Words • Phrase speech • Fluent Speech • Activities for daily living, plans, hopes Psychometric Issues in Diagnosis • Low test-retest reliability on many instruments • Little investigation of specificity or validity of screening • • • • measures Lack sensitivity and specificity Severity scores quantifying social deficits needed Sometimes alternative thresholds are suggested for research vs clinical diagnoses Children of color or of less-educated parents less likely to receive ASD diagnosis than Caucasian kids or kids with well-educated parents (Mandell et al 2009) Psychometric Issues in Diagnosis • In a study of children with language disorder, both the ADOS and ADI- R were administered to children • Studied 21 children ages 6-9 • Correlation between instruments low (Bishop 2011) • Χ^2 (4) = 1.86, p= .762 Social Problems • Most universal, specific characteristic of ASD • Consistent and replicated across studies • Lack joint attention, theory of mind • Cannot correctly assign motives, understand someone’s goals, difficulty participating in spontaneous symbolic play • Other groups show problems with theory of mind but may not show same deficits in joint attention • Down Syndrome, severe hearing impairment • Pay proportionately less attention to people than objects • Spend less time than TD kids doing something that shows intent • Children are attached to mothers as much as age- and IQ-matched TD kids (Rogers et al., 1991) • Tend not to point, show objects – attention-sharing behaviors (Sigman et al., 1986) • Do not seem to recognize emotions (facial expression, gesture, nonverbal vocalizations of emotion) Restricted, Repetitive Behaviors • Verbal and nonverbal repetitive, stereotyped behaviors • More heterogeneous and context-dependent than social deficits • Including them on diagnostic instruments increases specificity with little change in sensitivity • One study showed only 9 of 2700 children with ASD diagnosis did not show any RRB’s (Lord et al., 2012) Restricted, Repetitive Behaviors • Four subdomains: • Motor stereotypies – lining things up, flipping things, step counting, unusual responses to sensory input, rocking • Some of these may be common in young children – clinicians must look at the number and intensity of behaviors to discriminate TD from ASD • Tend to emerge early in life but are somewhat malleable • Most common subdomain • Rituals and sameness – like Rain Man’s pancake Tuesday • Prevalent in about 25% of ASD population • Develop later than motor type, stable throughout life • Circumscribed interests – highly fixated or unusual interests • A particular movie, cartoon character, topic, the phone book, shoe size • Self-injurious behavior – hand flapping, hitting • Present in other disorders • More common in ASD than general population • Subdomains show different trajectories Language Delay • Language delay is not specific to ASD • Delays in receptive language may be specific to ASD as opposed to other communication disorders (Philofsky, Hepburn, Hayes, Hageran, & Rogers 2004) • Not yet connected to specific neurobiological problem • Language (particularly receptive language) scores correlate with IQ (specifically verbal) (Luyster et al., 2008) Prevalence • In 1990’s it was 1 per 2,000, including Asperger’s Syndrome 1 per 1,000 (Tanguay 2000) • Current prevalence rates around 1/150 to 1/100 for ASDs (Croen et al., 2002, Rice, 2009) • True increase in milder cases • True increase of all case types • More awareness • Problems with diagnostic instruments • Incorrect diagnoses • Studies differ in screening methods, diagnostic instruments, diagnostic criteria • Diagnosed 4x as often in males than females Diagnostic Criteria • Projects using ICD-10 criteria show prevalence around 1/2,000 (Autism) and 1/600 (Autism plus other pervasive developmental disorders) • Studies using less strict criteria show much higher prevalence rates • Bryson et al., 1988, 1/1,000 Used ABC (checklist) • Sugiyama and Abe (1989) used DSM-III and noted 1/760 • Ehlers and Gillberg (1993) set of criteria specifically designed to diagnose ASD found 1/143 Onset and Course • Symptoms are usually noted first in months 12-24 of a child’s life • Delayed language, odd play patterns, lack of social interaction • Pay attention to type, frequency, intensity of symptoms • Can experience developmental plateaus or regression • Rarely a severe regression after 2 years of normal development • Onset must occur by age 3 • Individuals generally improve throughout lives • Robust diagnosis • Sensitivity of .82 and specificity of .87 (Volkmar et al 1994) Common Comorbidities • 70% of ASD individuals have one comorbid disorder, up to • • • • 40% may have 2 or more (DSM-V) Medical conditions such as epilepsy and sleep problems somewhat common Comorbid diagnoses of ADHD, anxiety and depressive disorders, and developmental coordination disorder seen First degree relatives have higher incidence of major depression and social phobia than the rest of the population (Bolton et al., 1998) Relatives have 20% frequency of social phobia (Smalley et al., 1995) • 10 times higher than controls • Over half (64%) had first episode before the birth of autistic child Common Comorbidities? • Posited that autism shared genetic cause and thus comorbidities with: • Fragile X (no more than 2-5% have FRA-X mutation, Bailey et al., 1993) • Tuberous sclerosis (mostly seen in autistic people with severe deficits, Guiterrez et al., 1998) • Celiac disease (Pavone et al., 1997 study of 120 people with celiac disease showed none with diagnosis of autism based on DSM-III, nor celiac disease in the 11 patients with autism) Biological Contributions ? Genetics • Concordance rates in monozygotic versus dizygotic twins range from 60-91% (MZ), 0-10% (DZ) (Folstein and Rutter, 1977, Steffenburg et al., 1989, Bailey et al., 1995.) • Variation in behavioral and cognitive deficits as great within MZ pairs as between pairs • These findings suggest that autism is highly heritable (broad cognitive and social impairment) • Different sets of genes do not act to produce different symptoms Genetics • Gender disparity led some researchers to wonder if ASD linked to X chromosome • Hallmayer et al (1996) found no major gene effect on X chromosome causing autism • International Molecular Genetic Study of Autism Consortium (1998) found possible connections for regions on chromosomes 7 and 16 • Significance is not yet known • Found most often in those with severe language delays Neuroligins and Neurexins • Neuroligins and neurexins are the “building blocks” of synapses • Small percentage of those with ASD have mutations which can cause neurexin deletions • This affects synaptic formation and function • May increase risk for developing ASD Neuropharmacological Studies • Cook and Leventhan (1996) noted that serotonin may be involved in many of the symptoms of autism • This is neither surprising nor particularly helpful • One study found people with ASD have autoantibodies to brain serotonin receptors (Todd and Ciaranello, 1985) • Two studies failed to confirm findings • People with ASD may have increased 5-HT on blood platelets Electroencephalography • ASD people unlikely to show more EEG abnormalities than the normal population • This is nonspecific and not particularly helpful Neuroimaging and Neuropathological Studies • General difficulty confirming neuroimaging findings • Different measures used to correlate with brain function, generally weak measures • Future studies will probably add comparisons of ADHD or language impairments to ASD • Increased volume in amygdala, hippocampus, and limbic system, decreased Purkinje cells • We don’t know how high functioning these individuals were • Harris et al. (2006) claimed to find abnormal patterns of activity in the brains of those with ASD and claimed near-perfect identification • This has not been replicated • Ongoing NIMH effort to form neurobiologically based dimensions to help diagnose ASD, but no published data yet Macroencephaly • 14-30% of ASD people have increase in head circumference (Fombonne et al., 1999) • Developed in early/middle childhood (Lainhart et al), but this finding relies on retrospective data • Increase is in temporal, parietal, and occipital lobes (not frontal) • Cause and effects of increase unknown • Not correlated with IQ, verbal ability, seizure, other mental illness Neuropsychological Patterns • Compared to normal controls, ASD people have intact or superior performance in attention, simple memory, simple language, and visual-spatial domains • Impaired in skilled motor tasks, complex memory, complex language, and reasoning • While interesting, not helpful in understanding much more about autism than is already known Neuropsychological patterns • Executive functioning deficits • Impairments in cognitive flexibility and set-shifting • Nonspecific to autism • May underlie theory of mind deficits • Price et al., (1990) study of 2 individuals with widespread frontal damage (early in developmental process) • Both showed severe impairment in role-taking, also seen in ASD and is part of theory of mind Neuropsychological Patterns • 20 ASD, 19 Down’s Syndrome kids, 20 TD kids • Two tasks: • Delayed Non-Matching to Sample • Rule-learning ability, visual recognition memory • Amygdala and hippocampus • Delayed Response • Working memory and response inhibition • Dorsolateral PFC • Social and nonsocial stimuli task Vaccines Vaccines • One study published in a medical journal concluded a link • • • • between vaccines (MMR) and autism Article was fully retracted in 2010 Lead author Andrew Wakefield had many undeclared conflicts of interest and manipulated some of his data Found guilty of serious medical misconduct and no longer allowed to practice medicine Study has been disproved many times since its original publication in 1998 Vaccines • DeStefano et al (2013) evaluated 256 ASD kids and 752 TD kids matched on birth year and sex, ages 613 • Confirmed diagnoses via ADI-R and ADOS • Study inclusion criteria required elevated scores on both assessments and onset before 36 months • Obtained vaccination histories, • Looked at total antigen exposure, amount per day • No significant differences Environmental Factors • Mouridsen et al. studied 328 children with autism, “autism-like conditions,” or “borderline child psychosis” • Children with autism had greater incidence of births in March or August • Children with autistic-like conditions most often born in May and November • Essentially, this means nothing. Environmental Factors • Rutter 1998 study looked at institutionalized children in Romania sent to the UK • Experienced horrible living conditions • 7/165 met criteria for autism based on a screening questionnaire • Severe social deprivation may lead to autistic-like social and emotional difficulties • Could less severe social deprivation interact with genes to cause autism in some kids or worsen symptoms? Treatment Medication • Tricyclics and SSRI’s seem to decrease hyperactivity, anger, and compulsive behaviors (Gordon et al., 1993, Brodkin et al., 1997) • Neuroleptics may be effective in reducing hyperactivity, impulsivity, aggressiveness (Potenza et al., 1999) • (Obviously) • Pharmacological interventions have a limited role Medication • Double-blind study of 40 kids, given placebo or haloperidol • Given semistructured interviews, rated by teachers on Connors Parent-Teach Questionnaire • While on haloperidol, kids showed significant decreases in withdrawl, hyperacitvity, abnormal object relationships, fidgetiness, negativeism, angry affect, and lability of affect as compared to baseline or placebo Therapy • The key is early intervention! • This means developing specific measures is crucially important • Two types • Traditional behavior learning (ABA) • Focus is on adult control and child compliance, uses positive reinforcement • Social-pragmatic teaching (child-centered therapy, incidental teaching) • Focuses mainly on social skills • Focus of therapy is on increasing independence and quality of life Applied Behavior Analysis • Gold standard • Based on behaviorism • Uses positive reinforcement to decrease maladaptive and unwanted behaviors, increase adaptive behaviors • Uses negative reinforcement/negative punishment when necessary (rarely) • Treatment can begin when children are as young as 3 • In severe cases, focus is on compliance • Intensive (20-40 hours/week), one-on-one format • Targets a wide range of skills • Includes parents (and important others when possible – siblings, teachers, etc.) ABA Effect Size Metrics • Meta-Analysis of 22 studies (Virués-Ortega 2010) • Different outcome reported: full-scale IQ (18 studies), nonverbal IQ (9), receptive language (10), expressive language (9), language composite (5), adaptive behaviorcommunication (10), adaptive behavior – daily living skills (10), adaptive behavior – socialization (10), adaptive behavior – motor skills (3), overall composite adaptive behavior (14) • Mean age ranged from 22.6-66.3 months • Some studies included PDD-NOS ABA • ABA positively impacted: • IQ – 1.19 no evidence of effect from intensity/duration • Nonverbal IQ – 0.67 • Receptive language – 1.48 • Expressive language – 1.47 • General language skills – 1.07 • Communication – 1.45 • Daily living skills – 0.62 • Socialization - 0.68 • Motor skills – 0.71 • Adaptive behavior (composite score) – 1.09 • ABA leads to long-term medium to high positive effect sizes for adaptive behaviors • Social support (siblings) moderate response (Hastings, 2003) CBT • CBT has been modified for ASD kids presenting with • • • • • anxiety Goal is to remediate social skills in the hopes that this will translate to decreased anxiety Random assignment to 16 sessions of CBT or 3-month waitlist CBT model emphasized adaptive behavior, parental training, school consultation 78% of CBT group had reductions in anxiety on Clinical Global Impressions-Improvement scale compared to 8.7% of waitlist CBT did not reduce self-reports of anxiety Virtual Interactive Environments • Used for teaching social skills, theory of mind • Practical situations, such as taking the bus, going to the grocery store • Some studies use robots (can play games with kids) • Interactions (eye gaze, tough, contact time) increase • Not yet known if this generalizes to real life Complimentary and Alternative Medicine Therapies (Mostly pseudoscience) • Auditory integration Training • Facilitated communication • Nonverbal/severely handicapped people are suddenly writing emotional, grammatically correct messages • This is due to the facilitator (Bomba et al 1996) • Viamin B6 and Magnesium • 30% of children showed improvement in Martineau (1998) study. • Other studies show no improvement • Changes in nutrition • All are ineffective Genetics Some combination of: • Neurexin and neuroligin abnormality • Chromosome 16 abnormality • Chromosome 7 inversion Genetics Some combination of: • Neurexin and neuroligin abnormality • Chromosome 16 abnormality • Chromosome 7 inversion Genetics Some combination of: • Neurexin and neuroligin abnormality • Chromosome 16 abnormality • Chromosome 7 inversion Therapy • Core Features ABA • Social difficulties • Restricted, repetitive behaviors Biological Substrate Some combination of: • Enlarged amygdala, hippocampus • Abnormal fusiform gyrus • Macroencephaly • Decreased Purkinje cells • Increased 5-HT Biological Substrate Some combination of: • Enlarged amygdala, hippocampus • Abnormal fusiform gyrus • Macroencephaly • Decreased Purkinje cells • Increased 5-HT Medication • SSRI’s • Antipsychotics Secondary Features Environment • Abuse • Social support • • • Intellectual disability Inattention Motor problems References Anderson, D.K., Oti, r.s>, Lord, C., & Welch, K. 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