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By John Gever, Senior Editor, MedPage Today

Published: May 24, 2012

Only about half of children with an autism spectrum disorder received the diagnosis before they reached age 5, and once diagnosed, most were given psychotropic drugs, federal survey data indicated.

Interviews with parents or guardians of 1,420 children identified as having autism spectrum disorders revealed that the median age at diagnosis was 5, according to Beverly Pringle, PhD, of the National Institute of Mental Health, and colleagues in a Data Brief issued early Thursday by the National Center for Health Statistics.

And fully 40% were diagnosed at age 6 and older.

Parents of only 18.7% were told of the diagnosis before the child reached age 2, the researchers found.

The findings came from the 2011 Survey of Pathways to Diagnosis and Services, conducted with 4,032 parents and guardians of children identified in an earlier survey as having neurobehavioral development disorders, including intellectual disability, developmental delay, or autism spectrum disorders.

The new Data Brief contained summary statistics for the children with autism spectrum disorders.

Other key findings include:

56% of children were taking at least one psychotropic medication including stimulants (32%), mood stabilizers (26%), antidepressants (20%), sleep enhancers (19%), and/or antipsychotic drugs (14%).

Among children younger than 12, 91% were using some type of healthcare service for their disability, such as speech therapy or social skills training, and 61% were using at least three.

Primary care providers and psychologists were the most common source of autism spectrum diagnoses before age 5, while older children were more often diagnosed by physician specialists.

Pringle and colleagues observed that the variety of psychotropic medications used in children with an autism spectrum disorder could have at least two explanations.

It may reflect the presence of "co-occurring symptoms," or perhaps the "absence of clear practice guidelines for psychotropic medications in children with autism spectrum disorders," they wrote.

They also expressed concern about the pattern of healthcare service use identified in the survey.

Although most children were receiving some type of therapy, 12% were not.

Moreover, only about 40% of parents reported behavioral intervention or modification services, "the most well-established and efficacious intervention for autism spectrum disorders."

John Gever

Senior Editor

John Gever, Senior Editor, has covered biomedicine and medical technology for 30 years. He holds a B.S. from the University of Michigan and an M.S. from Boston University.

Now based in Pittsburgh, he is the daily assignment editor for MedPage Today as well as general factotum on the reporting side. Go Pirates/Penguins/Steelers!

http://www.medpagetoday.com/Pediatrics/Autism/32882? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: July 02, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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Action Points

Note that in this study, the presence of schizophrenia in parents was associated with an increased risk for autism spectrum disorders and, similarly, schizophrenia in a sibling was associated with an increased risk for autism spectrum disorders.

Point out that the findings in this study suggest that autism spectrum disorders, schizophrenia, and possibly bipolar disorder share common etiologic factors.

Autism spectrum disorder appears more likely for children with schizophrenia or bipolar disorder in their immediate family, suggesting common factors among the three, researchers found.

The autism risk was 2.9-fold higher with schizophrenia in parents and 2.6- to 12.1-fold elevated with schizophrenia in a sibling across various cohorts studied by Patrick F. Sullivan, MD, of the University of North Carolina at Chapel Hill, and colleagues.

The links were similar but lesser in magnitude for bipolar disorder in a first-degree family member, the group reported online in the Archives of General Psychiatry.

The findings suggest that schizophrenia, bipolar disorder, and autism are different manifestations of the same root causes.

The common factors could be shared DNA sequence variation, a common environmental risk factor the whole family is exposed to, or a gene-environment interaction, Sullivan and colleagues suggested.

"Genetic effects may be more likely given substantial heritability estimates for autism spectrum disorder, schizophrenia, and bipolar disorder along with evidence for relatively lesser but significant environmental effects," they wrote.

But that doesn't necessarily mean that all three should be lumped together into a single psychiatric classification just yet, the group pointed out.

Rather, "it is tenable that these disorders are more similar phenotypically than currently appreciated, and it might prove interesting to reevaluate the degrees of demarcation between these three disorders," Sullivan's group wrote.

Bipolar disorder has a well known etiologic and clinical overlap with schizophrenia.

Autism used to be "regarded as childhood schizophrenia because the impaired social interactions and bizarre behavior found in autism spectrum disorder were reminiscent of symptoms of schizophrenia," the researchers noted.

While the two were separated diagnostically around 1980, they explained, "several lines of evidence suggest that this distinction is not absolute."

The group examined histories of schizophrenia or bipolar disorder in first-degree relatives of individuals with autism spectrum disorder in three cohorts:

The national inpatient and outpatient registries in Sweden dating back to 1973, which included 25,432 autism spectrum disorder cases, each matched to 10 controls for sex, birth year, and sex of relatives

A registry of primarily outpatient facilities for treating autism in the Stockholm area, with 4,982 cases and 49,844 controls from 1984 through 2007

A database of standardized psychiatric assessment of conscripts for compulsory military service in Israel, which included 386 cases born in the 1980s and 436,311 controls

The link between autism spectrum disorder and family history of the other psychiatric disorders was consistently significant across the cohorts and categories studied.

The likelihood of autism spectrum disorder was 2.9-fold elevated with a parental history of schizophrenia in both the Swedish national cohort (95% confidence interval 2.5 to 3.4) and the Stockholm County cohort (95% CI 2.0 to 4.1).

Schizophrenia in a sibling raised the risk 2.6-fold in the Swedish national cohort and 12.1-fold in the Israeli conscription cohort, though with a larger 95% confidence interval of 4.5 to 32.0 that overlapped with the confidence interval of 2.0 to 3.2 in the national cohort.

"We speculate that the higher sibling odds ratio from Israel resulted from subjects with earlier onset schizophrenia, which has a higher sibling recurrence risk," Sullivan's group wrote.

Bipolar disorder in a parent was associated with:

90% elevated odds of autism spectrum disorder in the Swedish national cohort (95% CI 1.7 to 2.1)

60% elevated odds of autism spectrum disorder in the Stockholm cohort (95% CI 1.1 to 2.1)

The associations appeared stronger in autism spectrum disorder without a clinical indication of mental retardation but didn't vary by sex of either the relative or the autism case.

The Stockholm cohort didn't have sibling data available, while the Israeli cohort didn't have data on family history of bipolar disorder.

Another potential limitation of the Swedish national cohort was that it started collecting outpatient data only in 2001 and couldn't be used for prevalence estimates because it was not yet complete.

But variations in reporting from different healthcare providers were deemed unlikely to be correlated with family history of psychotic symptoms by the researchers.

The study was funded by the Swedish Council for Working Life and Social Research, the Swedish Research Council, and the Beatrice and Samuel A. Seaver Foundation.

The researchers reported having no conflicts of interest to disclose.

Primary source: Archives of General Psychiatry

Source reference:

Sullivan PF, et al "Family history of schizophrenia and bipolar disorder as risk factors for autism" Arch Gen Psychiatry 2012; DOI: 10.1001/archgenpsychiatry.2012.730.

http://www.medpagetoday.com/Pediatrics/Autism/33589? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Michael Smith, North American Correspondent, MedPage Today

Published: September 04, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

Note that this study documents a victimization rate for adolescents with an autism spectrum disorder which was substantially higher than the national prevalence estimates for the general adolescent population.

Point out that adolescents with an autism spectrum disorder and attention-deficit/hyperactivity disorder were significantly more likely to experience victimization, perpetration, and victimization/perpetration compared with those with only an autism spectrum disorder.

Nearly half of adolescents with an autism spectrum disorder (ASD) have been the victims of bullying, researchers reported.

In nationally representative surveys, adolescents with ASD were about four times more likely to be victimized than other adolescents, but no more likely to be bullies or to be both bullied and bullying, according to Paul Sterzing, PhD, of the University of California Berkeley, and colleagues.

On the other hand, they were significantly less likely to be victims than adolescents with mental retardation and had roughly the same risk as those with learning disabilities or speech impairments, Sterzing and colleagues reported online in Archives of Pediatrics & Adolescent Medicine.

Adolescents with developmental disabilities have previously been shown to be at increased risk for all aspects of bullying, both as victims and perpetrators, the researchers noted.

But there has been relatively little study of bullying in the context of ASD, which is worrying, they argued, since ASD adolescents may be "uniquely vulnerable to this form of aggression given the social and relational problems that are hallmarks of their condition."

To help fill the gap, they turned to the National Longitudinal Transition Study 2, a 10-year, five-wave prospective study of adolescents receiving special education services.

The study was designed to produce nationally representative estimates that would apply to students receiving special education services in the seventh through 12th grades or those in ungraded programs who were 13 through 16 years old on Dec. 1, 2000.

Prevalence estimates of bullying behavior were derived from parent interviews of 1,100 students with ASD and surveys of staff members from their schools.

The researchers compared those estimates with estimates of the same behaviors among students with mental retardation, learning disabilities, and speech impairments – conditions that overlap with ASD.

Sterzing and colleagues found, based on parental reporting, that:

46.3% of adolescents with ASD were bullied, compared with 48.8% of those with learning disabilities, 47% of those with speech impairments, and 56.7% of those with mental retardation.

The latter was significantly different from the rate for ASD adolescents, at P<0.01.

14.8% of adolescents with ASD were bullies, compared with 14% of those with learning disabilities, 9.4% of those with speech impairments, and 17.8% of those with mental retardation.

Those with speech impairment were significantly less likely, at P<0.05, to be perpetrators that those with ASD.

8.9% of adolescents with ASD experienced both victimization and perpetration, compared with 11.4%, 7.5%, and 15.5%, respectively, of those with learning disabilities, speech impairments, or mental retardation.

Those with mental retardation were significantly more likely than ASD adolescents, at P<0.01, to experience both aspects of bullying.

It's estimated that 10.6% of the general teen population falls victim to bullying. That makes the 46.3% for teens with ASD far higher, but, the researchers reported, they are about as likely to be bullies or to be both bullies and victims as the general adolescent population.

In multivariate models, Sterzing and colleagues reported:

Victimization was associated with having non-Hispanic ethnicity, attention-deficit/hyperactivity disorder, lower social skills, some form of conversational ability, and more classes in general education.

Bullying was associated with being white, having attention-deficit hyperactivity disorder, and getting together with friends at least once a week.

Victimization/perpetration was associated with being white non-Hispanic, having attention-deficit/hyperactivity disorder, and getting together with friends at least once a week.

The researchers cautioned that bullying involvement was not defined for respondents, possibly leading to reporting bias, and it was measured in a way that precluded assessment of frequency and duration.

Also, they noted, the study did not have multiple informants to measure bullying involvement.

The study had support from the Organization for Autism Research, Autism Speaks, and the National Institute of Mental Health.

The journal said the researchers made no financial disclosures.

Primary source: Archives of Pediatrics & Adolescent Medicine

Source reference:

Sterzing PR, et al "Bullying involvement and autism spectrum disorders: Prevalence and correlates of bullying involvement among adolescents with an autism spectrum disorder" Arch Pediatr Adolesc Med 2012; 166(9): 1-7.

http://www.medpagetoday.com/Neurology/Autism/34547? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Charles Bankhead, Staff Writer, MedPage Today

Published: September 23, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

High-functioning adults with autism exhibited variable brain responses to visual and auditory stimuli, suggesting that the condition may involve specific alterations in neural processing.

Note that the group reported that a distinction between the cortical and thalamic results may indicate a dissociation such that weak signal-to-noise may be a specific characteristic of cortical processing in autism.

High-functioning adults with autism exhibited variable brain responses to visual and auditory stimuli, suggesting that the condition may involve specific alterations in neural processing, investigators reported.

Detected by serial MRI brain scans, the variability, or unreliability, pertained only to evoked responses, not ongoing fluctuations in activity, reported Ilan Dinstein, PhD, of Carnegie Mellon University in Pittsburgh, and colleagues, in Neuron.

Standard deviations in cortical responses to stimuli differed significantly between autistic and normal adults (P<0.05), as did signal-to-noise ratios (P<0.05).

The differences persisted across trials of evoked visual responses, auditory responses, and somatosensory responses, the authors said.

"These findings reveal that abnormally unreliable cortical responses, even to elementary nonsocial sensory stimuli, may represent a fundamental physiological alteration of neural process in autism," Dinstein's group wrote.

"These results motivate a critical expansion of autism research to determine whether (and how) basic neural processing properties such as reliability, plasticity, and adaptation/habituation are altered in autism."

Autism research has followed two distinct pathways, each based on the premise that autism results from disordered general neural processing.

One approach has focused on identifying areas of the brain that respond abnormally during performance of social or cognitive tasks.

The approach is based on the assumption that specific behavioral impairments in autism are associated with dysfunction in particular brain areas, the authors noted in their background summary.

The second approach has centered on brain architecture and integrity of anatomical connections and functional synchrony between neurons in different parts of the brain.

Both approaches have generally given little attention to specific neural processing functions or characteristics that might underlie autism. Dinstein and colleagues sought to address the lack of information by examining the reliability of evoked responses in adults with autism.

Investigators used MRI to study cortical responses in visual, auditory, and somatosensory systems of 14 high-functioning adults with autism and 14 IQ-matched adults without autism.

Each study participant completed three experiments involving evoked responses to different types of stimuli:

A visual stimulus involving moving white dots

An auditory stimulus consisting of a series of pure tone beeps in both ears

A somatosensory stimulus in the form of air puffs from a hose on the back of a participant's hand

Cortical responses were captured by functional MRI.

The primary objective was to determine the reliability of responses to identical stimuli in the autistic and control groups.

Prior to the experiments, each participant completed a resting-state assessment, which allowed investigators to identify areas of the brain that had the most robust responses to each type of stimulus and also to establish baseline responses.

After determining the areas of greatest sensory activation, the investigators identified regions of interest within the visual cortex, auditory cortex, and secondary somatosensory cortex.

Selected by an automated procedure, the regions of interest comprised 200 adjacent voxels that exhibited the greatest activation to the stimuli in each hemisphere.

The mean response amplitudes across the three sensory experiments did not differ between the participants with autism and the control group.

However, the authors found significant differences in the reliability of responses in the autistic group. Trial-by-trial standard deviations, were significantly greater among the autistic participants, and signal-to-noise ratios (response amplitude divided by variability) were significantly smaller in the autistic group (P<0.05).

Also, the group reported that a distinction between the cortical and thalamic results may indicate a dissociation such that weak signal-to-noise may be a specific characteristic of cortical processing in autism.

However, they recommended caution in interpreting these results, because fMRI response amplitudes in thalamic nuclei were weaker than those in cortical areas, which limited the statistical power for comparing cortical and subcortical responses.

The results showed a trend toward a positive correlation between signal-to-noise ratios and IQ in the autistic group and a trend toward a negative association between the ratios and severity of autism symptoms.

"Determining the relationship between greater neural response variability and behavioral symptoms of autism will clearly require additional research," the authors wrote. "We speculate that poor response reliability may be directly related to the development of both secondary and core symptoms of autism."

The study was supported by the Simons Foundation, ISF and Bikura grants, Clore and Kahn fellowships, the Pennsylvania Department of Health, and NIH.

The authors reported no conflicts of interest.

Primary source: Neuron

Source reference:

Dinstein I, et al "Unreliable evoked responses in autism" Neuron 2012; 75: 981-991.

http://www.medpagetoday.com/Neurology/Autism/34919? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 Everyday Health, Inc. All rights reserved.

By Charles Bankhead, Staff Writer, MedPage Today

Published: September 23, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

High-functioning adults with autism exhibited variable brain responses to visual and auditory stimuli, suggesting that the condition may involve specific alterations in neural processing.

Note that the group reported that a distinction between the cortical and thalamic results may indicate a dissociation such that weak signal-to-noise may be a specific characteristic of cortical processing in autism.

High-functioning adults with autism exhibited variable brain responses to visual and auditory stimuli, suggesting that the condition may involve specific alterations in neural processing, investigators reported.

Detected by serial MRI brain scans, the variability, or unreliability, pertained only to evoked responses, not ongoing fluctuations in activity, reported Ilan Dinstein, PhD, of Carnegie Mellon University in Pittsburgh, and colleagues, in Neuron.

Standard deviations in cortical responses to stimuli differed significantly between autistic and normal adults (P<0.05), as did signal-to-noise ratios (P<0.05).

The differences persisted across trials of evoked visual responses, auditory responses, and somatosensory responses, the authors said.

"These findings reveal that abnormally unreliable cortical responses, even to elementary nonsocial sensory stimuli, may represent a fundamental physiological alteration of neural process in autism," Dinstein's group wrote.

"These results motivate a critical expansion of autism research to determine whether (and how) basic neural processing properties such as reliability, plasticity, and adaptation/habituation are altered in autism."

Autism research has followed two distinct pathways, each based on the premise that autism results from disordered general neural processing.

One approach has focused on identifying areas of the brain that respond abnormally during performance of social or cognitive tasks.

The approach is based on the assumption that specific behavioral impairments in autism are associated with dysfunction in particular brain areas, the authors noted in their background summary.

The second approach has centered on brain architecture and integrity of anatomical connections and functional synchrony between neurons in different parts of the brain.

Both approaches have generally given little attention to specific neural processing functions or characteristics that might underlie autism.

Dinstein and colleagues sought to address the lack of information by examining the reliability of evoked responses in adults with autism.

Investigators used MRI to study cortical responses in visual, auditory, and somatosensory systems of 14 high-functioning adults with autism and 14 IQ-matched adults without autism.

Each study participant completed three experiments involving evoked responses to different types of stimuli:

A visual stimulus involving moving white dots

An auditory stimulus consisting of a series of pure tone beeps in both ears

A somatosensory stimulus in the form of air puffs from a hose on the back of a participant's hand

Cortical responses were captured by functional MRI.

The primary objective was to determine the reliability of responses to identical stimuli in the autistic and control groups.

Prior to the experiments, each participant completed a resting-state assessment, which allowed investigators to identify areas of the brain that had the most robust responses to each type of stimulus and also to establish baseline responses.

After determining the areas of greatest sensory activation, the investigators identified regions of interest within the visual cortex, auditory cortex, and secondary somatosensory cortex.

Selected by an automated procedure, the regions of interest comprised 200 adjacent voxels that exhibited the greatest activation to the stimuli in each hemisphere.

The mean response amplitudes across the three sensory experiments did not differ between the participants with autism and the control group.

However, the authors found significant differences in the reliability of responses in the autistic group.

Trial-by-trial standard deviations, were significantly greater among the autistic participants, and signal-to-noise ratios (response amplitude divided by variability) were significantly smaller in the autistic group (P<0.05).

Also, the group reported that a distinction between the cortical and thalamic results may indicate a dissociation such that weak signal-to-noise may be a specific characteristic of cortical processing in autism.

However, they recommended caution in interpreting these results, because fMRI response amplitudes in thalamic nuclei were weaker than those in cortical areas, which limited the statistical power for comparing cortical and subcortical responses.

The results showed a trend toward a positive correlation between signal-to-noise ratios and IQ in the autistic group and a trend toward a negative association between the ratios and severity of autism symptoms.

"Determining the relationship between greater neural response variability and behavioral symptoms of autism will clearly require additional research," the authors wrote.

"We speculate that poor response reliability may be directly related to the development of both secondary and core symptoms of autism."

The study was supported by the Simons Foundation, ISF and Bikura grants, Clore and Kahn fellowships, the Pennsylvania Department of Health, and NIH.

The authors reported no conflicts of interest.

Primary source: Neuron

Source reference:

Dinstein I, et al "Unreliable evoked responses in autism" Neuron 2012; 75: 981-991.

http://www.medpagetoday.com/Neurology/Autism/34919? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 MedPage Today, LLC. All rights reserved

By Crystal Phend, Senior Staff Writer, MedPage Today

Published: October 08, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

Action Points

Almost half of autistic children go missing from caregivers at some point, usually putting themselves in danger, an online survey found.

Note that the risk of elopement rose with greater autism spectrum disorder severity.

Almost half of autistic children go missing from caregivers at some point, usually putting themselves in danger, researchers found.

More than half of them were gone long enough to cause concern, 65% had close calls with getting hit in traffic, and 24% were at risk of drowning during their escapade, according to an online survey by Paul A. Law, MD, MPH, of the Kennedy Krieger Institute in Baltimore, and colleagues.

Risk of elopement rose with greater autism spectrum disorder severity -- 9% for every 10 points on the Social Responsiveness Scale T score, they reported in the November issue of Pediatrics.

The frequency of "elopement" seen in the study may account in part for the roughly doubled mortality with autism spectrum disorder compared with the general population, the group suggested.

"These results highlight the urgent need to develop interventions to reduce the risk of elopement, to support families coping with this issue, and to train child care professionals, educators, and first responders who are often involved when elopements occur," they wrote.

Their study surveyed families of 1,218 children with autism spectrum disorders, with 1,076 unaffected siblings, using a questionnaire administered through the Interactive Autism Network online research database and registry.

Half of the affected children had autism, while another 19% had Asperger disorder. The rest had other autism spectrum disorders.

The prevalence of having wandered off at least once after age 4 (a cutoff set because running from safe spaces and adult supervision is more typical of toddlers) was 49% overall.

That rate was much lower among unaffected siblings than the children with autism spectrum disorders at all ages. Respective rates, for example, were:

11% versus 46% at ages 4 to 7

1% versus 27% at ages 8 to 11

"Advocacy groups have reported that children with ASD are more difficult to keep safe because of their wandering behavior, and that parents fear being viewed as neglectful when these children succeed in escaping safe spaces," the researchers noted.

However, given the low rate of wandering off among siblings, "it is doubtful that, as a group, these parents are remiss in keeping children safe," they pointed out.

The situations were highly stressful for parents, with 43% of those whose child eloped saying it kept them from sleeping well at night and 62% saying it kept the family from enjoying activities away from home.

More than half of the parents with experience in this regard said wandering off was one of the most stressful behaviors they had to cope with as a caregiver for their child.

Children, on the other hand, appeared to largely enjoy running off. Parents described their autistic child as a "happy, playful, or exhilarated" during the event, although those with Asperger disorder often appeared more anxious.

"In either case, much of the behavior appears goal-directed," the investigators noted. Half of the escapees appeared focused on going somewhere or doing something, while only about 10% seemed confused, in a fog, or sad and lost.

Children with autism spectrum disorder were most likely to wander off from home (74%), although stores and schools were common locations as well (40% and 29%, respectively).

At their peak, 35% of the children were trying to run off at least once a week and 29% made attempts multiple times a day.

The researchers cautioned that the findings may not generalize to all children with autism spectrum disorders because the families chose to participate in the registry, and the survey appeared to have some self-selection bias, with well-educated parents and a greater proportion being white.

Also, the study included only families with a living autistic child, so fatalities could not be estimated.

The study was supported by the Autism Research Institute, the Autism Science Foundation, Autism Speaks, the Global Autism Collaboration, and the National Autism Association.

The researchers reported having no conflicts of interest to disclose except for one co-author who is now employed by Autism Speaks, a financial supporter of the IAN Project through which the elopement survey was implemented.

Primary source: Pediatrics

Source reference:

Anderson C, et al "Occurrence and Family Impact of Elopement in Children With Autism Spectrum Disorders" Pediatr 2012; DOI: 10.1542/peds.2012-0762.

http://www.medpagetoday.com/Pediatrics/Autism/35196? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 MedPage Today, LLC. All rights reserved

By Cole Petrochko, Staff Writer, MedPage Today

Published: November 02, 2012

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston

Action Points

A policy statement on nonmedical interventions for children with autism spectrum disorders suggests that early, comprehensive, intense, and longer-duration interventions are most likely to assist with core deficits.

Note that strength of evidence from review of systematic reviews and intervention studies was not considered high and thus the policy committee could not distinguish among techniques nor assess characteristics of children most likely to benefit; further research was recommended.

Intensive behavior programs for autism spectrum disorders were moderately effective at improving core deficits, particularly when started shortly after diagnosis, but additional and stronger research on these programs is needed, a systematic review found.

A policy statement from the Evidence-based Practice Center on behavioral interventions for autism found that programs offering comprehensive, intense, and long-duration interventions started shortly after diagnosis and for at least 25 hours a week may offer the best outcomes, according to Margaret Maglione, MPP, of the Southern California Evidence-based Practice Center in Santa Monica, and colleagues.

Interventions should address social communication, language, play skills, and maladaptive behavior, they wrote online in Pediatrics.

The authors also noted that much of the evidence supporting individual programs was moderate to insufficient in strength and, as a result, they could not support one behavioral technique over others.

"Given the scope of the problem, there is a pressing need to clarify effective practices and to highlight gaps for additional intervention development," they said.

The study and development of a policy statement were the result of the Combating Autism Act of 2006.

The Maternal and Child Health Bureau of the U.S. Health Resources and Services Administration funded investigations into treatment for physical and behavioral aspects of treating autism.

The behavioral treatment statement included guidelines on nonmedical interventions "that address cognitive function and core deficits in children with autism and recommend priorities for future research."

It was written by an 18-member multidisciplinary panel with backgrounds in psychology, developmental pediatrics, child psychiatry, and education, as well as parents of children with autism.

The panel reviewed 33 systematic reviews and 68 intervention studies that included data on children or adolescents, included specific outcome data on participants with autism, reported outcome data on cognitive function or core deficits (including communication, language, social skills, behavior, restricted interest, and adaptive skills), and had a sample size of at least 10.

Interventions in each study were evaluated for strength and rated high, moderate, low, or insufficient.

Guidelines were drafted based on input from the panel, the Evidence-based Practice Center, researchers at the University of California Los Angeles, and parents of children with autism.

None of the interventions were of high strength.

Interventions of moderate strength included comprehensive intervention programs that are effective at improving core deficits, had greater intensity of treatment (in hours per week), and longer duration (in months).

This also included autonomous social skills programs for high-functioning children and adolescents and Picture Exchange Communication System programs for children with little or no verbal language.

The authors suggested a number of characteristics needed to develop future comprehensive programs, such as addressing deficits in:

Social communication, including appropriate joint attention capability or inability to respond to one's name

Language, including lack of or delay in developing functional language, echolalia, or repetitive use of language

Play skills, including lack of spontaneous make-believe play, lack of social interest, and excessive interest in one type of play

Adaptive function and behavior, including excessive preoccupation with specific objects and rituals, difficulty adjusting to minor schedule changes, and aggression to others or property and self-injurious behavior

The program, they also suggested, should offer ongoing parent education in specific intervention techniques applied, which would "help transfer the newly acquired skills to home and community settings."

They added that "timely treatment can help maximize the impact of interventions on young children's development and prevent further developmental delays or deterioration of functioning in older individuals."

They concluded that "none of the evidence reaches the level of high strength according to established standards," and recommended that "additional large, well-designed, controlled trials" be carried out.

They also emphasized that "not all children who attend these programs will make significant gains regarding core deficits; the scientific literature is not clear as to which individual participant characteristics are associated with success of various approaches."

The authors had no conflicts of interest to declare.

Primary source: Pediatrics

Source reference:

Maglione MA, et al "Nonmedical interventions for children with ASD: recommended guidelines and further research needs" Pediatrics 2012; 130(S2): S169-S178; DOI: 10.1542/peds.2012-09000.

http://www.medpagetoday.com/Pediatrics/Autism/35710? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 MedPage Today, LLC. All rights reserved.

By Nancy Walsh, Staff Writer, MedPage Today

Published: November 12, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

It remains unclear whether mothers who develop common infections during pregnancy are more likely to have autistic children.

[U]Note that no significant associations were seen for either autism spectrum disorder or infantile autism according to the trimester in which a maternal infection occurred.[/Ub]

It remains unclear whether mothers who develop common infections during pregnancy are more likely to have autistic children, Danish researchers said.

Overall, no associations were seen for infections and autism spectrum disorder, although a twofold increased risk was seen for the more severe subtype of infantile autism (adjusted HR 2.3, 95% CI 1 to 5.3) following maternal influenza infection, according to Hjördis Ósk Atladóttir, MD, PhD, of the University of Aarhus in Denmark, and colleagues.

There also was a threefold increase in risk for infantile autism when mothers reported having had a febrile episode lasting for a week or more (aHR 3.2, 95% CI 1.8 to 5.6), the researchers reported online in Pediatrics.

But the analysis was exploratory and involved multiple testing, so the findings could have resulted from chance, they cautioned, noting that this was a "great limitation" of the study.

Animal studies have suggested that activation of the maternal immune system in pregnancy, such as from infection, can lead to abnormalities in fetal neural development.

But previous studies looking at risks in women and their offspring have turned in conflicting results and have not considered specific infections or timing of the infection.

Atladóttir and colleagues analyzed data from the Danish National Birth Cohort, which enrolled 101,033 pregnant women between 1996 and 2002.

The researchers interviewed participating women by telephone at 17 and 32 weeks' gestation and again when the child was 6 months old.

The specific infections women were asked about included

respiratory tract infections, pyelonephritis, cystitis, influenza, cough, vaginal yeast infection, venereal warts, genital herpes, and labial herpes.

When possible, diagnoses were verified through discharge diagnoses in the Danish National Hospital Register.

In the analysis, adjustments were made for maternal and paternal age, parity, and smoking, as well as for parental education and psychiatric disorders, but there were no adjustments for multiple comparisons.

Among their offspring, 976 were diagnosed with autism spectrum disorder and 342 with infantile autism.

Mean follow-up was about 10 years.

Adjusted hazard ratios for autism spectrum disorders and these infections were all nonsignificant and ranged from 0.7 (95% CI 0.4 to 1.4) for genital herpes to 1.8 (95% CI 0.9 to 3.9) for pyelonephritis.

Other than influenza, none of the infections were significantly associated with infantile autism, with aHRs ranging from 0.9 (95% CI 0.3 to 1.5) for genital herpes to 1.2 (95% CI 0.9 to 1.7) for cystitis.

The significant risk seen for infantile autism after a prolonged episode of fever in the mother also was seen for autism spectrum disorder (aHR 1.6, 95% CI 1 to 2.5), the researchers reported.

There also was a small elevation in risk of the two disorders with maternal use of antibiotics.

For instance, when sulfonamides were used at any time during pregnancy, or if penicillin was given in the second or third trimesters, the risk rose by about 50%.

Exposure to macrolides at any time during pregnancy also was associated with a greater risk for infantile autism (aHR 2.2, 95% CI 1.1 to 4.4).

But no significant associations were seen for either autism spectrum disorder or infantile autism according to the trimester in which a maternal infection occurred.

In discussing their findings, the researchers pointed to uncertainty as to the reason why a week-long febrile episode should influence autism risk.

"We do not know whether a febrile episode in our study is acting as a proxy for a specific infectious illness, specific severity of illness, a specific immune response, or if the direct action of hyperthermia on the fetus is potentially harmful," they observed.

It could also be "a coincidental finding," they noted.

Similarly, it's unclear whether the association of antibiotic use and increased risk resulted from the illness, the treatment, immune response in the mother, or chance.

Several other methodologic limitations included the possibility of bias in participation, the general nature of the questions asked of the mothers, and the likely inaccurate reporting of influenza.

"Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for [autism spectrum disorder] and infantile autism," Atladóttir and colleagues stated.

However, they were unable to rule out the possibility of an association, and called for "further research on this important topic."

The study was funded by the Aarhus University Research Foundation, the Aase and Ejnar Danielsen Foundation, and the Augustinus Foundation.

The authors reported no financial conflicts.

Primary source: Pediatrics

Source reference:

Atladóttir H, et al "Autism after infection, febrile episodes, and antibiotic use during pregnancy: An exploratory study" Pediatrics 2012; DOI: 10.1542/peds.2012-1107.

http://www.medpagetoday.com/Pediatrics/Autism/35879? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 MedPage Today, LLC. All rights reserved.

By Charles Bankhead, Staff Writer, MedPage Today

Published: November 27, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Action Points

Two studies used imaging techniques to evaluate patients with autism spectrum disorder.

One study using quantitative magnetic resonance imaging found that individuals with autism spectrum disorder have significant differences in cortical volume associated with separable variations in cortical thickness and surface area.

Another study using positron emission tomography (PET) indicates excessive microglial activation in multiple brain regions in young adult subjects with autism spectrum disorder.

Young adults with autism spectrum disorder (ASD) had significant variation in cortical volume, thickness, and surface area compared with an age-matched control group, MRI brain scans showed.

The differences in people with ASD consisted primarily of increased cortical thickness in frontal-lobe regions (P<0.003 versus control group) and reduced surface area in the orbitofrontal cortex and posterior cingulum (P<0.05), wrote Christine Ecker, PhD, of King's College London, and colleagues in Archives of General Psychiatry online.

Differences in surface area accounted for a majority of the variation in cortical volume, but in almost a third of cases, neither cortical thickness nor surface area could account for the variation in volume.

A comparison of imaging results and scores on a standardized autism test showed some correlation between cortical volume and symptom severity.

"Differences in cortical volume observed in individuals with ASD may be underpinned by cortical thickness and surface area, which exhibited statistically independent sources of variability," the authors said.

"These two factors are likely to be the result of distinct developmental pathways that are modulated by different neurobiological mechanisms.

Both cortical thickness and surface area would thus benefit from being explored in isolation to elucidate the etiology and neurobiology of ASD," they added.

Another study in the same issue of the journal showed that individuals with ASD have excessive microglial activation in multiple brain regions, as revealed by PET imaging.

Autopsy and neuroimaging studies have demonstrated multiple differences in brain anatomy of individuals with ASD compared with the general population.

Most prior studies employed volumetric analyses. Because of the specific anatomical characteristics of cortical volume, determining the driving factors underlying the differences might lead to better understanding of ASD's biologic basis.

Ecker and colleagues studied 84 young (mean age 26) right-handed men and an age-matched control group of 84 men.

Participants in the ASD were assessed by means of the Autism Diagnostic Interview-Revised (ADI-R) to confirm the diagnosis of childhood autism, and current symptoms were determined by the Autism Diagnostic Observation Schedule.

Their intellectual capacity was evaluated by a standard IQ test, which showed that all members of the ASD group were high functioning.

All participants underwent quantitative MRI studies, which included a standardized data-acquisition protocol.

The ASD and control groups did not differ with respect to full-scale or verbal IQ, but the ASD group demonstrated significantly poorer performance IQ (P=0.001). The groups also did not differ in total brain volume or mean cortical thickness.

After performing a correlational analysis of multiple comparisons across the brain, the authors found that the ASD group had significantly greater cortical thickness in the left lateral prefrontal cortex (P<0.003), including peaks in the ventrolateral and rostrolateral prefrontal cortex.

The individuals with ASD also had significantly decreased cortical thickness in the right anterior temporal lobe (P<0.04) and significantly decreased cortical volume in a region of the bilateral orbitofrontal cortex (P<0.005). The ASD and control groups did not differ significantly in terms of overall surface area.

Surface area did differ between the groups in certain regions of the brain.

ASD was associated with decreased surface area in the right dorsolateral prefrontal cortex and bilateral orbitofrontal cortex; left anterior temporal gyrus and anterior cingulate; and supplementary and presupplementary motor cortices.

Surface area was decreased in the temporoparietal junction.

The authors found that about two-thirds of the between-group differences in cortical volume could be attributed to overlap with cortical thickness (8%), surface area (56%), or both (5%).

In the ASD group, the authors found statistically significant correlations between the cortical thickness in the left dorsolateral front cluster and higher scores on the ADI-R communication and repetitive domains (P=0.02, P=0.009) and total ADI-R scores (P=0.01).

Significantly reduced cortical volume in the orbitofrontal cortex was associated with increased symptom severity on the ADI-R social domain (P=0.03 and P=0.04 for left and right hemispheres).

"Thus, individuals with more severe social autistic symptoms at ages 4 to 5 years displayed significantly smaller cortical volume of the orbitofrontal lobes," the authors wrote, adding that their results should be considered exploratory and require future replication.

In the second study, Japanese investigators reported significantly increased tracer uptake on PET imaging in multiple regions of the brain in young men with ASD. The study involved 20 patients with ASD (age 18 to 31; mean IQ 95.9) and 20 age- and IQ-matched healthy men without ASD.

The most prominent increase in tracer uptake was evident in the cerebellum. Other areas with increased uptake were the midbrain, pons, fusiform gyri, and anterior cingulate and orbitofrontal cortices (P<0.05 for all values).

The pattern of regional binding potential (tracer uptake) did not differ between the cases and control group, only the magnitude, which was greater in the ASD group than the control group in all regions assessed.

"Our results indicate excessive microglial activation in multiple brain regions in young adult subjects with ASD," wrote Norio Mori, MD, PhD, of Hamamatsu University in Hamamatsu City, and colleagues.

"The similar distribution pattern of regional microglial activity in the ASD and control groups may indicate augmented but not altered microglial activation in the brain in the subjects with ASD," they said.

The study had some limitations.

It was performed on a population basis and the participants were high-functioning ASD patients; the study did not include ASD subtypes in which immunologic abnormality may have been more prominent.

Also, the radiotracer used has a significant nonspecific binding.

The study by Ecker and colleagues was supported by the Medical Research Council.

Ecker reported no conflicts of interest.

Co-author Edward Bullmore, MD, PhD, is a shareholder and part-time employee of GlaxoSmithKline.

The study by Mori and colleagues was supported by the Japanese Ministry of Education, Culture, Sports, Science, and Technology, and by the Ministry of Health, Labor, and Welfare.

The authors had no conflicts of interest.

Primary source: Archives of General Psychiatry

Source reference:

Ecker C, et al "Brain surface anatomy in adults with autism. The relationship between surface area, rotical thickness, and autistic symptoms" Arch Gen Psychiatry 2012.

Additional source: Archives of General Psychiatry

Source reference:

Suzuki K, et al "Microglial activation in young adults with autism spectrum disorder" Arch Gen Psychiatry 2012.

http://www.medpagetoday.com/Neurology/Autism/36125? utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=

© 2012 MedPage Today, LLC. All rights reserved.