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The Implications of DSM V: Changes in Diagnostic Outcomes in An Adult Clinical Sample Re-Diagnosed According to the Proposed DSM V is a talk to be given at IMFAR on Saturday. Given the very high focus on the DSM V from the online autism community, I had hope that this study might shed some light on the topic. IMFAR is a forum for preliminary work, and the abstract in this case shows that:

Background: Major changes in diagnostic criteria are proposed for DSM-V, including the collapsing of autistic disorder, Asperger’s disorder and PDD-NOS into a single diagnosis; ‘autism spectrum disorder (ASD)’. The effects of these changes are as yet unclear; will individuals diagnosed by current criteria still meet diagnostic criteria with the proposed diagnostic scheme? While some work has been reported addressing this issue in children, no studies in adults have been published to date. Adults, including those first receiving a diagnosis in adulthood, are an important, and somewhat neglected, group in autism spectrum clinical services and research and are the focus for the present study.
Objectives: To review the effect of proposed DSM V diagnostic algorithms on the diagnostic outcome of a clinical sample of patients assessed for ASD in adulthood.

Methods: Diagnostic information was reviewed for 100 consecutive adult patients who attended the Behavioural Genetics Clinic, a specialist clinic providing assessment of ASD at the Maudsley Hospital, London. Original diagnosis was made in accordance with the ICD-10 criteria. Diagnostic assessment included a detailed neuropsychiatric interview, Autism Diagnostic Interview-Revised (ADI-R) and / or Autism Diagnostic Observation Schedule (ADOS) pending consent to contact parents/parental availability and physical examination. Information from the ICD 10 algorithm, ADI-R, ADOS and neuropsychiatric assessment reports was used to recode diagnostic outcomes in accordance with the proposed DSM 5 ASD algorithm as posted by the American Psychiatric Association.

Results: Data will be presented showing the degree of agreement between current ICD 10 diagnoses (Asperger’s Syndrome, Childhood Autism, Atypical Autism, Pervasive Developmental Disorder-not otherwise specified) and the proposed new DSM 5 diagnosis of ASD.

Conclusions: Implications for proposed changes to diagnostic criteria will be highlighted.

The abstract tells us little about results, just that they will be “presented showing the degree of agreement between current ICD 10 diagnoses (Asperger’s Syndrome, Childhood Autism, Atypical Autism, Pervasive Developmental Disorder-not otherwise specified) and the proposed new DSM 5 diagnosis of ASD”

The International Meeting for Autism Research (IMFAR) started on Wednesday with a press conference and a pre-conference program focused on stakeholders. I was fortunate to be able to attend last year, but not this year. I did call in to the press conference, though and it brought back some of the excitement for me.

Before going on, note that the press conference is covered at the Thinking Person’s Guide to Autism (by people who actually attended!) as IMFAR 2012 Press Conference

The press conference highlights a number of studies which are about to be presented at the conference. It was stressed that IMFAR is a conference where the abstracts are reviewed before being approved, but the studies are not peer-reviewed as in a journal. It is a conference for very new results.

One study highlighted was Beyond ASD: Developmental Outcomes of High Risk Siblings. This is a follow on study to the well publicized baby siblings study that found about 19% recurrence risk for baby siblings of autistic children. This is the study that looks at the other 81%, the kids who did not get an autism diagnosis. Short answer–even among the children who did not get an autism diagnosis, the baby siblings had more autistic traits than children who were not baby siblings of autistics.

Here’s the conclusion from the abstract:

Conclusions: At three years, HR [high Risk]children without an ASD had higher levels of ADOS symptom severity, and lower levels of developmental functioning than LR [Low Risk]children. They were more likely to occupy clusters characterized by lower levels of developmental functioning, and less likely to occupy a cluster characterized by higher levels of developmental functioning and low levels of symptom severity. Descriptively, two-thirds of HR children occupied Clusters 1 and 2, characterized by normative outcomes, whereas one third occupied Clusters 3, 4, and 5, characterized by elevated ADOS severity, lower developmental quotients, or both. These results suggest an early ‘broader autism phenotype’ in HR siblings characterized by ASD symptoms sub-threshold for diagnosis and/or developmental delays.

and the summary:

A new study presented at the International Meeting for Autism Research examined the development of the younger siblings of children with an Autism Spectrum Disorder (ASD). ASDs are developmental conditions characterized by problems with interaction, communication and repetitive behaviors. Previously, an international consortium of researchers found that almost one in five of the younger siblings of children with an ASD themselves developed an ASD. The researchers’ new findings suggest that of the younger siblings who did not develop an ASD, one in three faces challenges at three years of age.

The challenges faced by these younger siblings of children with ASD include slight delays in verbal and nonverbal functioning and somewhat elevated levels of autism-related characteristics. Examples of a child’s autism-related characteristics—which are not as severe as those of children with an ASD—include lower levels of back-and-forth play with others, and lower levels of pointing to express interest in what is going on around them. Overall, the researchers say, the majority of high-risk siblings are developing typically at three years of age, but a minority face challenges that appear to reflect subtler forms of ASD-related problems. Follow-up of these children through school age is necessary to understand their long-term outcomes.

The second study highlighted was Shared Decision Making (SDM) and the Treatment of Autism Spectrum Disorders (ASDs). My guess is that the themes presented in the summary below will not come as a great surprise to those who have read parent narratives on the internet. I.e. that parents look to pediatricians for treatment options for their autistic kids, but the doctors often don’t see autism treatment to be something they can do.

The goal of this qualitative study was to describe factors influencing shared decision making for treatment decisions by pediatricians and parents of children with autism spectrum disorders (ASD). We conducted in-depth interviews of 20 pediatricians and 20 parents of children with ASD 2-5 years of age. The analysis of the interview transcripts revealed that many pediatricians did not view treatment for autism spectrum disorders to be within their scope of practice or competence. Parents did not view their pediatrician as knowledgeable or invested in making treatment recommendations. We also found that parents often independently pursue treatments, not benefiting from professional guidance regarding safety and effectiveness. Results from this study indicate substantial barriers to shared decision making between pediatricians and families in the care of autism. Research is needed in order to understand how best to help 1) parents have realistic expectations of their pediatrician and 2) improve training of pediatricians to be effective partners in care of children with ASDs and their families

The third highlighted study was Oxytocin’s Impact on Social Cognitive Brain Function in Youth with ASD. The study member who presented this for the study called it “very exciting and very preliminary”. Two features of this study stand out immediately: (1) it is a double-blind, crossover, randomized control study and (2) it includes fMRI (functional magnetic resonance imaging).

Here is the summary:

We are presenting the preliminary data from the first ever double blind, placebo controlled study of changes in brain activity in children with an ASD (ages 7-18) after a single dose of oxytocin. The initial results indicate that oxytocin, administered via nasal spray prior to the scan, increased activity in brain regions known to process social information. Oxytocin is a naturally occurring substance that is produced in the brain and plays a role in regulating social abilities.

These results provide the first, critical steps towards devising more effective treatments for the core social deficits in autism which may involve a combination of validated clinical interventions with an administration of oxytocin. Such a treatment approach will fundamentally alter for the better our understanding of autism and its treatment.

There were two more studies highlighted at the press conference but, I’m sorry to say, I was not able to listen to those presentations.

Measuring Interactive Developmental Pathways in ASD: A Dual-Domain Latent Growth Curve Model Symptoms, Diagnosis & Phenotype – Cognition & Behavior: Early ASD

As children with autism spectrum disorders (ASD) grow up, they embark on quite different developmental pathways. Some individuals learn to live independently, maintain friendships, and find work, many require some support in their daily lives, and still others experience many challenges. Understanding how very young children with ASD develop important early skills can provide vital clues that might help predict these various pathways. For example, researchers have suggested that greater social interest and awareness in children with ASD may have a positive impact on language, which in turn may have a positive influence on other aspects of learning and development. This model of “cascading” effects is intuitively appealing but has not been validated in ASD. The Canadian “Pathways in ASD” Study (funded by CIHR and other provincial governments and foundations) is uniquely able to shed light on this issue as it is the largest prospective follow-up study of very young children with this disorder. As part of this study, we used information about 365 2-to-4-year-olds with ASD to examine whether such cascades occurred across early social competence and language abilities in the year after diagnosis. On average, the children made significant progress in social competence and remarkable gains in language abilities over that year. Within this one-year period, greater change in social competence in the first year was associated with more growth in language skills. However the reverse wasn’t true: early language ability had a much smaller effect on changes in children’s social competence. These findings therefore support the idea of early developmental cascade effects. Early advantages and gains in social competence may lead to advantages in other domains. However, children whose very early social skills lag farther behind at time of diagnosis are also less likely to show language progress. This study highlights the importance of early interventions that focus on emerging social competence (versus only language skills), as these are likely to “spill over” across other developmental pathways.

and

Head Lag in Infants At Risk for Autism

This new prospective study of six-month-old infants at high genetic risk for autism identified weak head and neck control as a red flag for autism spectrum disorder (ASD) and language and/or social developmental delays. Researchers at the Kennedy Krieger Institute concluded that a simple “pull-to-sit” task could be added to existing developmental screenings at pediatric well visits to improve early detection of developmental delays.

While previous studies have shown that head lag indicates developmental delays in children with cerebral palsy and preterm infants, postural control in infants at risk for ASD had not been examined. In this research, Dr. Landa and her team assessed infants in a “pull-to-sit” task, a simple measure of postural control in infants. The findings suggest that motor delays may have an important impact on child development.

Four of the editors from The Thinking Person’s Guide to Autism are at IMFAR this year. Their post on the press conference is already up: IMFAR 2012 Press Conference

If you watch for autism related news stories you likely have seen multiple stories on a paper out Friday in the American Journal of Psychiatry: Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism (full paper available online). The researchers studied brain structure in children and compared those who went on to be diagnosed with autism to those who did not. They found differences in white matter between the two groups. In particular fiber tracks were different.

Here’s figure 1 (click to enlarge) from the paper to give you an idea of what they mean by fiber tracks. Check the brain cartoons on the right. Then check the actual data in the graphs. These are “significantly different” trajectories for these measurements. They are not clear differences that could lead to a diagnostic tool.

Here is the abstract:

Objective:

Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.
Method:

The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity.
Results:

The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values.
Conclusions:

These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.

If the idea of differences in fiber tracks seems somewhat famiiliar, last year Eric Courchesne at UCSD reported at IMFAR about
Abnormally Accelerated Development of Higher-Order Long-Distance Cerebral Tracts In ASD Infants and Toddlers. The paper was highlighted at the IMFAR press conference (and discussedhere at Left Brain/Right Brain.

At the press conference David Amaral mentioned similar work at the IMFAR press conference last year.

At 51:20 in the video above, Prof. Amaral speaks on the work that precocious brain growth at 4-6 months of age in infants and is most prominently present in children with regression.

“..despite the fact that the regression, the behavioral regression, takes place at 18 months or 24 months, the brain changes actually started taking place at 4 to 6 months. So it actually casts a doubt on the idea that a vaccine, the MMR vaccine for example that’s taken at 12 to 18 months, would be actually the precipitating factor because things were starting much much earlier than that.”

The talk that Prof. Amaral was speaking about was Total Cerebral Volume Is Associated with Onset Status In Preschool Age Children with Autism.

C. W. Nordahl1, A. Lee1, M. D. Shen1, T. J. Simon1, S. J. Rogers1, S. Ozonoff2 and D. G. Amaral1, (1)Psychiatry and Behavioral Sciences, UC Davis M.I.N.D. Institute, Sacramento, CA, (2)Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UC Davis, Sacramento, CA
Background: Autism is a heterogeneous disorder, and multiple behavioral and biological phenotypes likely exist. One well-characterized behavioral phenotype is onset status. While some children with autism exhibit symptoms very early in life, others experience a regression or loss of previously acquired skills. There is currently very little known about the neural substrates associated with these two different behavioral trajectories in autism.

Objectives: We examined the relationship between total brain volume and onset status in a large sample of 2-4 year old children with autism spectrum disorder (ASD) (n = 48, early onset, n = 58, regression) and a comparison group of age-matched typically developing children (TD) (n = 55).

Methods: Diagnoses and autism severity were based on ADOS and ADI-R scores and clinical judgment by trained, experienced psychologists. Developmental quotients (DQ), verbal quotients (VQ) and nonverbal quotients (NVQ) were based on the Mullen Scales. Onset status was categorized based on parent reports from related ADI-R questions. Total cerebral volume was compared between autism onset groups as well as relative to age-matched typically developing controls. Autism severity and DQ were also evaluated in relation to brain volume and onset status.

Results: Children who exhibited regression had significantly larger total brain volumes than children with early onset autism (p = .004). Total brain volume in the early onset ASD group did not differ from the TD group, whereas total brain volume was significantly larger in the children with regression. Moreover, children with regression had significantly lower VQ (p = .03) and higher (i.e. more severe) ADOS social and communication scores (p = .02). Total brain enlargement remained significant even after controlling for these variables. There were no significant correlations between total brain volume and VQ or ADOS scores.

Conclusions: Total brain enlargement has been reported in children with autism under the age of five. However, behavioral associations with abnormal brain enlargement have not been fully explored. Our findings suggest that abnormal brain enlargement in autism is associated with a parent-reported regressive pattern of onset and more severe symptoms involving both developmental impairment and ASD severity.

The idea that autism, even regressive autism, has signs as early as 6 months is challenging to some groups on two levels. First the idea that autism involves physical differences in the brain. Second that these differences are present well before regression, or well before vaccines which are sometimes proposed as precipitating events.

The study itself has limitations, one being generalizability. It makes a lot of sense to monitor siblings of autistics since the recurrence risk is high and the chances of collecting data on autistics is higher than in the general populaiton. However, this leaves us with the question: are the types of autism found in siblings (familial autism) representative of all forms of autism?