AUTISM SPECTRUM DISORDER. DSM-V Criteria Criterion A: Persistent deficits in social communication and interaction Can include social-emotional reciprocity,

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 PDD-NOS. Did not find discrete categories.

• Categories were collapsed into Autism Spectrum – PDD-NOS, 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 SchematicGenetics

• Unknown

Biological Substrate

• Unknown

Core Symptoms• Social Deficits• Restricted, repetitive

behaviors

Secondary Symptoms• 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 6-13

• 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 behavior-communication (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

GeneticsSome combination of:• Neurexin and

neuroligin abnormality• Chromosome 16

abnormality• Chromosome 7

inversion

Biological Substrate

Some combination of:• Enlarged amygdala,

hippocampus• Abnormal fusiform gyrus• Macroencephaly• Decreased Purkinje cells• Increased 5-HT

GeneticsSome combination of:• Neurexin and

neuroligin abnormality

• Chromosome 16 abnormality

• Chromosome 7 inversion

GeneticsSome combination of:• Neurexin and

neuroligin abnormality

• Chromosome 16 abnormality

• Chromosome 7 inversion

Biological Substrate

Some combination of:• Enlarged amygdala,

hippocampus• Abnormal fusiform gyrus• Macroencephaly• Decreased Purkinje cells• Increased 5-HT

Core Features

• Social difficulties

• Restricted, repetitive behaviors

Secondary Features

• Intellectual disability

• Inattention• Motor

problems

Therapy• ABA

Medication• SSRI’s• Antipsychotics

Environment• Abuse• Social support

ReferencesAnderson, D.K., Oti, r.s>, Lord, C., & Welch, K. (2009). Patterns of growth in adaptive social abilities among children with autism spectrum disorders. Journal of Abnormal Child Psychology, 37(7), 1019-1034.Baron-Cohen, S. (2009). The short life of a diagnosis. The New York Times. Available from www.newyorktimes.com/2009/11/10/opinion10baron-cohen.htmlAnderson, L.W., Campbell, M., Grega, D.M., Perry, R., Small, A.M., & Green, W.H. (1984). Haloperidol in the treatment of infantile autism, American Journal of Psychiatry, 141(10), 1195-1202.Baron-Choen, S., Leslie, A.M., & Frith, U. (1985). Does the autistic child have a “Theory of mine”? Cognition, 21(1), 37-46.Bertrand, J., Mars, A., Boyle, C., Bove, F., Yeargin-Allsopp, M., & Decoufle, P. (2001). Prevalence of autism in a United States population: The Brick Township, New Jersey, investigation, Pediatrics, 108(5), 1155-1161.Bishop, D.V. (1989). Autism, Asperger’s syndrome, and semantic-pragmatic disorder: Where are the boundaries? British Journal of Disordered Communication, 24(2), 107-121.Bishop, D. (2011). How common is autism? Notes & Theories blog on guardian.co.uk (7 June 2011). Available from: http://www.guardian.co.uk/science/blog/2011/jun/07/how-common-auatism-diagnosis.Bishop, S.L., Richler, J., & Lord, C. (2006). Association between restricted and repetitive behaviors and nonverbal IQ in children with autism spectrum disorders. Child Neuropsychology, 12(4-5), 247-267.Bowler, D.M. (1992). “Theory of mind” in Asperger’s Syndrome. Journal of Child Psychology and Psychiatry, 33(5), 877-893.Brieber, S., Neufang, S., Bruning, N., Kamp-Becker, I., Remschmidt, H., Herpertz-Dahlmann, B., … & Konrad, D. (2007). Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder. Journal fo Child Psychology and Psychiatry, 48(12), 1251-1258.Carey, B. (2012). New definition of autism may exclude many, study suggests. The New York Times, A1.Charman, T., Baird, G., Simonoff, E., Loucas, T., Chandler, S., Meldrum, D., & Pickles, A. (2007). Efficacy of three screening instruments in the identification of autistic-spectrum disorders. British Journal of Psychiatry, 191 554-559.Charman, T., Jones, C.R., Pickles, A., Simonoff, E., Baird, G., & Happe, F. (2011). Defining the cognitive phenotype of autism. Brain 1380, 10-21.

ReferencesCicchetti, D.V., Koenig, K., Klin, A., Volkman, F.R., Paul, R., & Sparrow, S. (2011). From Bayes through marginal utility to effect sizes: A guide to understanding the clinical and statistical significant of the results of autism research findings. Journal of Autism Developmental Disorders, 41(2), 168-174. Constantino, J.N., & Gruber, C.P. (2005). Social Responsiveness Scale Manual. Los Angeles: Western Psychological ServicesCroen, L.A., Grether, J.K., Hoogstrate, J., & Selvin, S. (2002). The changing prevalence of autism in California. Journal of Autism Developmental Disorders, 32(3), 207-215.Dautenhahn, K., & Werry, I. (2004). Toward interactive robots in autism therapy, Pragmatics and Cognitions, 12(1), 1-35.Dawson, G., Webb, S.J., & McPartland, J. (2005). Understanding the nature of face processing impairment in autism: Insights from behavioral and electrophysiological studies. Developmental Neuropsychology, 27(3), 403-424.Dominick, K.C., Davis, N.O., Lainhart, J., Tager-Flusberg, H., & Folstein, S. (2007). Atypical behaviors in children with autism and children with a history of language impairment. Developmental Disabilities, 29(2), 145-162.Ecker, C., Marquand, A., Mourao-Miranda, J., Jonston, P, Daly, E.M., Brammer, M.J., … & Murphy, D.G. (2010). Describing the brain in autism in five dimensions-magnetic resonance imaging-assisted diagnosis of autism spectrum disorder using a multiparameter classification approach. Journal of Neuroscience, 30(32) 10612-106623.Elsabbagh, M., Mercure, E., Hudry, K., Chandler, S., Pasco, G., Charman, T., … & Johnson, M.H. (2012). Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Current Biology, 22, 1-5.Folstein, S., & Rutter, M. (1977). Infantile autism: A genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry, 18(4), 297-321.Fombone, E. (2002). Prevalence of childhood disintegrative disorder. Autism, 6(2), 149-157.Fombonne, E. (2003). Epidemiological surveys of autism and other pervasive developmental disorders: An update. Journal of Autism and Developmental Disorders, 33(4), 365-382.Geschwind, D.H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Science, 15(9), 409-416.

ReferencesGillespie-Lynch, K., Sepeta, L., Wang, Y., Marshall, S., Gomez, L., Sigman, M., & Hutman, T. (2012). Early childhood predictors of the social competence adults with autism. Journal of Autism Developmental Disorders, 42(2), 161-174.Gotham, K., Risi, S., Pickles, A., & Lord, C. (2007). The Autism Diagnostic Observation Schedule: Revised algorithms for improved diagnos validity. Journal of Autism Developmental Disorders, 37(4), 613-627.Harris, G.J., Chabris, C.F., Clark, J., Urban, T., Aharon, I., Steele, S. … & Tager-Flusberg, H. (2006). Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging. Brain Cognition, 61(1), 54-68.Hazlett, H.C., Poe, M.D., Gerig, G., Styner, M., Chappell, C., Smit, R.G., & Piven, J. (2011). Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years. Archives of General Psychiatry, 68(5), 467-476.Insel, T.R., & Cuthbert, B.N. (2009). Endophenotypes: Bridging genomic complexity and disorder heterogeneity, Biological Psychiatry, 66(11), 988-989.Jones, W., Carr, K., & Klin, A. (2008). Absence of preferential looking to the eyes of approaching adults predicts level of social desirability in 2-year-old toddlers with autism spectrum disorder. Archives of General Psychiatry, 65(8), 946-954.Juranek, J., Filipek, P.A., Berenji, G.R., Modahl, C., Osann, K., & Spench, M.aA. (2006). Association between amygdala volume and anxiety level: Magnetic resonance imaging (MRI) study in autistic children. Journal of Child Neurology, 21(12), 1051-1058.Kaiser, M.D>, Hudac, C.M., Shultz, S., Lee, S.M., Cheung, C., Berken, A.M., … & Pelphrey, K.A. (2010). Neural signatures of autism. National Academy of Science, 107(49), 21223-21228.Kim, S.H., & Lord, C. (2010). Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedules (ADOS). Autism, 3(4), 162-173.Kleinhans, N.M., Richards, T., Weaver, K., Johnson, L.C., Greenson, J., Dawson, G., & Aylward, E. (2010). Association between amygdala response to emotional faces and social anxiety in autism spectrum disroders. Neuropsychologia, 48(12), 3665-3670.Lee, H., Marvin, A.R., Watson, T., Piggot, J., Law, J.K., Law, P.A., … & Nelson, S.F. (2010). Accuracy of phenotyping of autistic children based on Internet implemented parent report. American Journal of Medicine, 153B(6), 1119-1126.Leekam, S. Tandos, j., McConachie, H., Meins, E., Parkinson, K., Wright, C., … & Le Couteur, A. (2007). Repetitive behaviours in typically developing 2-year-olds. Journal of Child Psychology and Psychiatry, 48(11), 1131-1138.Lord, C., & Bishop, S.L. (2010). Autism spectrum disorders: Diagnosis, prevalence, and services for children and families, Social Policy Report. Society for Research in Child Development, 24(2), 1-21.

References• Lord, C., Luyster, R., Ruthrie, W., & Pickles, A. (2012). Patterns of Developmental trajectories in toddlers with autism spectrum disorders. Journal of

Consulting and Clinical Psychology.• Lord, C., Petkova, E., Hus, V., Gan, W., Lu, F., Martin, D.M., … & Risi, S. (2012). A Multivariate Study of the Clinical Diagnosis of Different Autism

Spectrum Disorders. Archives of General Psychiatry, 69(3), 306-313.• Lord, C., Risi, S., DiLavore, P.S., Shulman, C., Thurm, A., & Pickles, A. (2006). Autism from 2 to 9 years of age. Archives of General Psychiatry, 63(6),

694-701.• Luyster, R., Gotham, K., Guthrie, W., Coffing, M., Petrak, R., Pierce, K., & Lord, C. (2009). The Autism Diagnostic Observation Schedule – toddler

module: A new module of a standardized diagnostic measure for autism spectrum disorders. Journal of Developmental Disorders39(9), 1305-1320.• Parsons, S., & Mitchell, S. (2002). The potential of virtual reality in social skills training for people with autistic spectrum disorders, Journal of

Intellectual Disability Research, 46(5), 430-443.• Pelphrey, K.A., Shultz, S., Hudac, C.M., & Vander, B.C. (2011). Research review: Constraining heterogeneity: The social brain and its development in

autism spectrum disorder. Journal of Child Psychologica Psychiatry, 52(6), 631-644.• Piven, J., Arndt., Bailey, J., & Andreasen, N. (1996). Regional brain enlargement in autism: A magnetic resonance imaging study. Journal of the

American Academy of Child and Adolescent Psychiatry, 35(4), 530-536.• Piven, J., Gayle, J., Landa, R., Wzorek, M., & Folstein, S. (1911). The prevalence of fragile X in a sample of autistic invididuals diagnosed using a

standardized interview. Journal of the American Academy of Child and Adolescent Psychiatry, 30(5), 825-830. • Regier, D.A.E., Narrow, W.E.E., Kuhl, E.A.E., & Kupfer, D.J.E. (2011). The conceptual evolution of DSM-5. Washington DC: American Psychiatric

Publishing Inc.Richler, J., Huerta, M., Bishop, S.L., & Lord, C. (2010). Developmental trajectories of restricted and repetitive behaviors and interests in children with autism spectrum disorders. Developmental Psychopathology, 22(1), 55-69.

• Sanders, S.J., Ercan-Sencicek, A.G>, Hus, V., Luo, R., Murtha, M.T., Moreno-De_Luca, D., … & State, M.W> (2011). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neurology, 70(5), 863-885.

• Sparks, B.F., Friedman, S.D>, Shaw, D.W., Aylward, E.H., Echelard, D., Artru, A.A. … & Dager, S.R. (2002). Brain structural abnormalities in young children with autism spectrum disorders. Neurology, 59(2), 184-192.

• Tanguay, P.E. (2000). Pervasive developmental disorders: A 10-year review, Journal of American Academy of Child Adolescent Psychiatry, 39(9), 1079-1095.

• Veenstra-Vanderweele, J., Christian, S.L., & Cook, E.H., JR. (2004). Autism as a paradigmatic complex genetic disorder. Annual Review of Genomics Human Genetics, 5, 379-405.

• Virtues-Ortega, J. (2010). Applied behavior analytic intervention for autism ine arly childhood: Meta-analysis, meta-regression, and dose-response meta-analysis of multiple outcomes, Clinical Psychology Review, 30, 387-399.

• Walker, D.R., Thompson, A., Zwaigenbaum, L., Goldberg, J., Bryson, S.E., Mahoney, W.J., … & Szatmari, P. (2004). Specifying PDD-NOS: A comparison of PDD-NOS, Asperger syndrome and autism. Journal of American Academy of Cild and Adolescent Psyciatry, 42(2), 172-180.

• Wood, J., Drahota, A., Sze, K., Har, K., Chiu, A., & Langer, D.A. (2009). Cognitive behavioral therapy for anxiety in children with autism spectrum disorders: a randomized, controlled trial, Journal of Psychology and Psychiatry, 50(3), 224-234.