The 2017 International Meeting for Autism Research (IMFAR)

May 10, 2017

Scientists from Around the World Discuss the Latest Findings on the Diagnosis, Causes and Treatments of Autism Spectrum Disorder

SAN FRANCISCO, CA (May 10, 2017) – The International Society for Autism Research (INSAR), a scientific and professional organization devoted to advancing knowledge about autism spectrum disorders, convened more than 2,000 researchers, autism specialists, students, advocates, self-advocates and other stakeholders from 40 countries for the 16th Annual International Meeting for Autism Research (IMFAR), the world’s largest scientific gathering on autism research, from May 10 through May 13 at the Marriott Marquis Hotel in San Francisco, CA.

Researchers and clinicians exchanged and disseminated the latest scientific findings and stimulated progress in autism research into the nature, causes and treatments for ASD during a series of scientific and educational panels, oral sessions and poster presentations. The meeting also featured demonstrations of innovative technologies and events designed for stakeholders and special interest groups.

HIGHLIGHTED ABSTRACTS

The following studies were featured at the press conference on May 10:

Wearable Sensor-Based Physiological and Physical Activity Biomarkers for Use In Laboratory And Naturalistic Environments To Assess Arousal And Repetitive Motor Movements In Individuals With Autism Spectrum Disorder

  1. S. Goodwin, Northeastern University, Boston, MA

SUMMARY:

Despite autism being widely recognized as the fastest growing and most costly neurodevelopmental disorder worldwide, there is no specific biomarker, laboratory test, or behavioral assessment procedure to identify, characterize, or monitor its progression. Autism is defined exclusively by past and present behavior determined from developmental history interviews, parent reporting on current behavior, and structured and semi-structured tasks that involve social interaction between an examiner and a child. However, recent advances in wearable computing is making it possible to capture data in laboratory, clinical, school, and home settings on an unprecedented scale. This presentation will share results from two lines of research that employ wearable biosensors in individuals with autism. The first involves data collection in 43 severely affected children with autism and demonstrates significantly higher and less variable heart rate responses to various psychological, social, and sensory demands as compared to a group of typically developing children. Moreover, six distinguishable subgroups within the autism group were identified based on their heart rate patterns, even after accounting for age, medication status, and functioning ability. In the second line of research, wearable movement sensors and pattern recognition algorithms are employed as automated measures of stereotypical motor movements in six severely affected individuals with autism. On average, automated hand flapping and body rocking recognition rates with 90% accuracy compared to frame-by-frame coded videos were achieved, and shown to maintain their accuracy over a three-year period. Identifying more objective and automated physiological and physical activity measures has the potential to transform our ability to better understand the pathophysiology of autism, enhance gold-standard assessments, aid in subtype identification, individualize treatment protocols, monitor treatment efficacy, and track developmental outcomes.

ABSTRACT:

Background: Despite autism spectrum disorder (ASD) being widely recognized as the fastest growing and most costly neurodevelopmental disorder worldwide, there is no specific biomarker, laboratory test, or behavioral assessment procedure to identify, characterize, or monitor its progression. ASD is defined exclusively by past and present behavior determined from developmental history interviews, parent reporting on current behavior, and structured and semi-structured tasks that involve social interaction between an examiner and a child.

Objectives: Describe wearable sensor-based physiological and physical activity technologies enabling multimodal assessments of autonomic arousal and repetitive motor movements in ASD in both laboratory and naturalistic environments, and review their utility for biobehavioral phenotyping and response to intervention in ASD.

Methods: Ubiquitous and wearable computing is making it possible to capture data in laboratory, clinical, school, and home settings on an unprecedented scale. Coupled with advances in pattern recognition algorithms and large-scale computing, semi-automated measures of physiology and behavior are emerging including wireless sensors for monitoring physiological arousal and wireless 3-axis accelerometers and pattern recognition algorithms that can automate the detection of stereotypical hand flapping and body rocking.

Results:  Results from two lines of research will be reported. The first employs wireless measures of autonomic nervous system (ANS) activity and demonstrates that severely affected children with ASD have different cardiovascular response patterns to various psychological, social, and sensory demands, including substantially higher and less variable heart rate (HR) than a typically developing group of age-sex matched peers. Moreover, in a follow-up replication study repeating the same assessment protocol in 43 severely affected children with ASD, 6 distinguishable subgroups within the ASD sample were identified who display normal, high, and extremely high HR, along with unreactive (‘stabile’) and reactive (‘labile’) response patterns using time series-based cluster analysis. In the second line of research, wireless 3-axis accelerometers and pattern recognition algorithms are employed as automated measures of stereotypical motor movements (SMM) in six severely affected individuals with ASD. Using five time and frequency domain kinematic features and a C4.5 decision tree classifier, average automated hand flapping and body rocking recognition rates of 89.5% in the laboratory and 88.6% in the classroom were achieved. Moreover, a direct replication wherein the same six individuals with ASD were observed three years later in their classrooms while wearing 3, 3-axis accelerometers to determine whether previously trained sensor-based classifiers maintain accuracy over time will be reported. Comparing automated recognition results for two different classifiers – Support Vector Machine and Decision Tree – using our previously established feature set yielded average accuracy across all participants over time ranging from 81.2% to 99.1% for all combinations of classifiers and features.

Conclusions: Identifying more objective and automated physiological and physical activity measures has the potential to transform our ability to better understand the pathophysiology of autism, enhance gold-standard assessments of ASD, aid in subtype identification, individualize treatment protocols, monitor treatment efficacy, and track developmental outcomes.

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Effects of a Parent-Training Intervention on Service Access and Employment for Youth with ASD

  1. L. Taylor1,2, R. M. Hodapp2, M. M. Burke3, S. N. Waitz-Kudla2 and C. Rabideau2, (1)Vanderbilt University Medical Center, Nashville, TN, (2)Vanderbilt Kennedy Center, Nashville, TN, (3)University of Illinois at Champaign-Urbana, Champaign, IL

SUMMARY:

When youth with autism spectrum disorder (ASD) leave high school, they move into an adult service system that is under-funded and difficult to navigate.  Difficulty accessing disability services has significant implications for those youth, as it leads to challenges obtaining and maintaining work and post-secondary educational positions. In this study, we tested a new intervention to improve service access and post-secondary outcomes for youth with ASD, by improving parents’ ability to advocate for adult disability services. The study included 41 families, who were randomly assigned to an intervention group or a wait-list control group. Compared to parents in the control group, those who took the intervention learned more about adult services, reported themselves more skilled and comfortable advocating on behalf of their son or daughter, and reported greater empowerment. In preliminary analyses, these improvements in parents’ ability to advocate were related to better outcomes for their sons and daughters. Specifically, greater improvement in parental empowerment was related to more services being received by the son or daughter with ASD 6 months after the intervention. There was some suggestion that, relative to the control group, sons and daughters with ASD from the intervention group were receiving more disability services, and had more positive employment and post-secondary educational outcomes. These promising findings indicate a need to test this new intervention in a larger group to see if participating in a parent advocacy intervention does, indeed, relate to better youth outcomes during the transition to adulthood.

ABSTRACT:

Background: When youth with autism spectrum disorder (ASD) leave high school, they encounter an adult service system that is underfunded and difficult to navigate; this serves as a significant barrier to accessing appropriate services and support. In response, our group developed the Volunteer Advocacy Program-Transition (VAP-T), which equips parents to more effectively navigate the adult service system on behalf of their son/daughter with ASD. In initial findings from a small randomized controlled trial (RCT), we found that relative to control group parents, those who participated in the VAP-T knew more about adult services, and felt more empowered and skilled in advocating. It is unclear, however, whether increased parental knowledge/empowerment leads to improved transition outcomes for youth.

Objectives: To test whether parent participation in the VAP-T led to increased service access and higher rates of community employment/post-secondary education (PSE) for transition-aged youth with ASD.

Methods: We examined the efficacy of the VAP-T using an RCT, waiting-list control design with families of youth with ASD who were within 2 years of high school exit. After completing pre-test measures, families were randomly assigned to the intervention group or a wait-list control. Parents in the intervention group met weekly for 12 weeks; each session lasted 2.5 hours. Sessions covered aspects of the adult service system (e.g., Vocational Rehabilitation, post-secondary education programs, SSI, SSDI) and advocacy skills. All youth had ASD diagnoses confirmed using the Autism Diagnostic Observation Schedule-2 administered by research-reliable clinicians.

38 families (19 treatment, 19 control) have completed the 6-month follow-up thus far. At this time, 55% of youth were in high school and 45% had exited. The sample of youth was 18% female, and 32% had an intellectual disability. Outcomes, measured six months after the intervention group completed the VAP-T, included the number of services youth were receiving and whether youth were currently working in the community or in a PSE program.

Results: Youth with ASD whose parents were in the treatment group were more than twice as likely as the control group to be working in the community or in PSE (47% vs. 21%), Fisher’s Exact Test p-value = .09. Group effects were more pronounced for those out of school; 86% of treatment group youth who had exited high school were working in the community or in PSE, compared to 30% of control group youth, Fisher’s Exact Test p-value = .04. Relative to the control group, treatment group participants may be receiving more services (3.60 vs. 3.00), although the difference was not statistically significant. Further analyses will examine whether intervention effects on service access depend on high school exit (in/out of high school) or whether the youth has an intellectual disability.

Conclusions: Training parents how to navigate the adult service system may lead to higher rates of employment/PSE participation for youth with ASD, and perhaps to better service access. Discussion will highlight the importance of intervening at the level of the family, when working to strengthen environmental supports for youth with ASD during the transition to adulthood.

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Impact of a Supported Screening Program to Increase Identification and Assessment of Latino Children at Risk for ASD

  1. J. Anthony1, K. Linas1, M. Biel2, R. Mendez1, S. C. Dos Santos-Arquinio1 and D. Jacobstein1, (1)Center for Child and Human Development, Georgetown University, Washington, DC, (2)Georgetown University, Washington, DC

SUMMARY:

There continues to be strong evidence of disparities in identification of ASD, age at the time of diagnosis, referral, and treatment for Latino children. The research presented here describes the development of a “Supported Screening” model that more effectively identifies Latino toddlers at risk for ASD, offering an opportunity for important early intervention. Supported Screening includes (1) activities for families around developmental milestones; (2) culturally-appropriate adaptation of the parent-completed modified checklist for autism in toddlers (M-CHAT) screening tool and its administration; (3) training for health center staff on ASD; and (4) screening and care coordination by bilingual/bicultural family navigators with relevant professional and personal experience. We studied the “Supported Screening” model at a large urban health center serving predominantly Central American Latino families. In the year before the study, very few toddlers were even screened for autism risk — less than 10 percent of Latino 18-30 month olds—and no children were identified to be at risk for ASD. At the end of the study using the “Supported Screening” model, more than 90 percent of the toddlers were screened during well-child visits. Four percent were identified to be at risk and referred for more specific ASD testing. This rate mirrors the rate of positive screens found in studies of U.S. English-language toddlers. Adoption of the “Supported Screening” model may help to reduce disparities in rates of diagnosis and treatment among Latino children, based on identification of community and provider needs which inform outreach, family engagement, training, and clinical procedures.

ABSTRACT:

Background: Screening in primary care is an important step in identifying young children with ASDs, expediting early behavioral and educational interventions. However, despite evidence that formal screening improves accuracy of identification over informal clinical assessment, there is far from universal use of ASD-specific screening tools with use is lower still with Spanish-speaking patient populations. Moreover, there continues to be strong evidence of disparities in identification, age at the time of initial diagnosis, referral, and treatment for Latino children compared to non-Latino white. Here, we present evidence for the effectiveness of an 18-month trial of Supported Screening (SS)—developed and implemented through a community participatory process to enhance the uptake of universal screening for ASDs in a large primary care center serving a primarily Latino population and increase identification and further assessment of children with ASD.

Objectives: The goals of SS are to enhance the identification of ASDs and other developmental delays in Latino children by increasing: (1) screenings conducted at 18- and 24-month well-child visits; (2) positive screens; and (3) successful referrals and timely evaluations.

Methods: SS was implemented at a large Federally Qualified Health Center serving a primarily urban Latino population in Washington, D.C and involved formative research with families, primary care providers (PCPs) and staff to inform: (1) family outreach activities and resources; (2) practice-wide training for PCPs and staff, and (3) services of Family Navigators (FN) with lived experience who provided support to families with a child identified at risk for ASD as well as ongoing care coordination with early intervention and medical providers. Screens and referrals were tracked for the approximately 7000 0-36 month old children per year, 70% of whom were identified as Latino.

Results: Formative research, including cognitive interviewing, resulted in adaptation of M-CHAT and its administration (verbal, combined screening and follow-up, implementation by FNs and PCPs) and comprehensive training emphasizing engaging families/addressing barriers, coupled with available consultation. Training resulted significant increases in staff knowledge of autism, screening and factors that increase caregiver disclosure of developmental concerns. The percentage of children screened rose from under 10% prior to the onset of SS to almost 90%. PCPs completed only a small number of screens at the onset of SS but almost 50% by the end. Records indicated that no children were identified at risk for ASD in the year prior to SS; however, by the end of the trail 4% of eligible children screened positively on the M-CHAT and were referred for services, a rate comparable to those found in other Spanish language populations.

Conclusions: Universal screening for ASDs in a center serving predominantly Latino families and successful follow-up of positive screens was facilitated by assessment of community/provider needs, increased staff skills in culturally appropriate family engagement, screening, and referral, and FNs integrated into the health provider system. Attention to these issues increase disclosure of developmental concerns by Latino families, produced improved attitudes of providers and families toward early screening and referral for ASDs, helping to reduce disparities in rates of diagnosis and treatment.

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Interaction Between Human Sexual Dimorphism and ASD Neurobiology

  1. J. Sanders1 and D. M. Werling2, (1)UCSF, San Francisco, CA, (2)Psychiatry, UCSF, San Francisco, CA

SUMMARY:

Autism spectrum disorders (ASDs) are diagnosed approximately 3-5 times more frequently in males than females, suggesting that females may be protected from the impact of ASD risk factors. We reasoned that this female protective effect is likely driven by biological processes that differ between males and females, and that are also altered in ASD. To identify such biological processes, we compared the expression of genes in unaffected males and females in the human brain from fetal development through adulthood. Excluding genes on the X and Y sex chromosomes, we see few differences in gene expression between males and females across development, however, genes that mark microglia, the immune cells of the brain, have higher expression in males during the mid- to late-fetal period. Previous research has shown that these microglial genes are also expressed at higher levels in the ASD brain. Therefore, microglial activity appears to sit at the intersection of sex-differential neurobiology and ASD neurobiology. We hypothesize that increased microglial activity and/or elevated expression of microglial genes in males during fetal development could act to sensitize males to ASD risk factors. In contrast, the comparatively reduced microglial activity at this developmental stage may protect females from the full impact of ASD risk factors, including disruptive genetic mutations.

ABSTRACT:

Background: The 4:1 male to female sex bias is one of the most consistent and striking observations in autism spectrum disorder (ASD). One explanation for this sex bias is the existence of a female protective effect (FPE), in which a greater burden of ASD risk factors are required for a diagnosis of ASD in females than in males. Direct observation of de novo ASD risk factors in genomic analysis supports this hypothesis, however indirect assessment of sibling ASD recurrence risk in epidemiological studies finds little supporting evidence for the FPE. Understanding the nature and mechanism of this protection may hold great potential for therapeutic strategies.

Objectives: To assess the role and potential mechanism of female protection in ASD

Methods: To explain the discordant genomic and epidemiological evidence for the FPE we developed a simulation of ASD risk in families to estimate the power to detect a difference in the burden of de novo mutations vs. sibling recurrence risk. Should the FPE exist, it must act through sexually dimorphic processes, including gene expression. We therefore also compared gene expression data from male and female brain samples in the BrainSpan dataset ranging from mid-fetal to adult developmental stages to identify such sex differences in neurobiology.

Results:  Under a quantitative model of ASD risk (Gaugler et al.2014), in which 50% of ASD risk in the population comes from unique environmental exposure, 47% comes from common inherited genetic variants and 3% comes from rare de novo mutations, we estimated the power to detect the FPE. Considering de novo mutations we achieve 80% power with a sample of about 500 ASD families, consistent with genomic literature. Furthermore, by combining exome and CNV data for over 5,500 ASD cases we consistently observe an increased burden of ASD risk factors in females, to a similar extent as predicted by the simulation. In contrast, the power to detect a significant difference in sibling recurrence rate in 10,000 ASD families remains below 30%. The FPE hypothesis is therefore also consistent with the epidemiologic literature. To explore the nature of the FPE, we assessed differential gene expression using RNA-Seq from over 1,200 region- and age-specific samples from males and females. We find similar developmental trajectories of gene expression in both sexes, with the exception of genes specific to microglia that are enriched in males during mid-late fetal development. These genes overlap with those observed in co-expression modules previously observed to be upregulated in ASD brains.

Conclusions: The FPE is the leading hypothesis of the underlying mechanism of ASD sex bias, with strong supporting evidence from genomic studies. The existing large-scale epidemiological analyses remain under-powered to corroborate this finding. Analysis of human transcriptome data identifies higher expression of microglial genes during male fetal development and finds that these genes overlap with those over-expressed in the post mortem ASD brain. This cellular and molecular pathway may sensitize males to ASD risk factors, and may account for the apparent female protective effect in ASD.

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Randomised Trial of a Prodromal Intervention for Infants at High Risk for Autism: Longitudinal Outcomes to Age Three Years

  1. Green1, E. Jones2, T. Gliga3, M. W. Wan4, A. Pickles5, V. Slonims6, G. Pasco7, M. Elsabbagh8, R. Bedford9, T. Charman10 and M. H. Johnson3, (1)University of Manchester, Manchester, England, United Kingdom, (2)Birkbeck, University of London, London, UNITED KINGDOM, (3)Centre for Brain and Cognitive Development, Birkbeck University of London, London, United Kingdom, (4)University of Manchester, Manchester, UNITED KINGDOM, (5)King’s College London, London, UNITED KINGDOM, (6)Evelina Children’s Hospital Guy’s and St Thomas’ NHS Foundation Trust, London, UNITED KINGDOM, (7)Institute of Psychiatry, London, UNITED KINGDOM, (8)McGill University, Montreal, CANADA, (9)Kings College, London, UNITED KINGDOM, (10)Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom

SUMMARY:

Previous research with infants at high familial risk of autism (infant siblings of children diagnosed with the condition) has found that the early markers for later autism diagnosis, such as reduced social interest or difficulties with attention and disengagement, can emerge towards the end of the first year. This study aimed to reduce these early ‘prodromal’ symptoms and thus lower the likelihood of the child developing difficulties associated with autism later on in childhood.  The intervention was an adapted version of an already established Video Interaction for Promoting Positive Parenting Programme (iBASIS-VIPP). Of the 54 families who took part in the study, 28 were randomly allocated to receive an average of 9 home-based visits from a therapist who used video-feedback to help the parents understand and respond to their baby’s individual communication style to improve infant attention, communication, early language development, and social engagement. These infants received the intervention for 5 months, from the age of 9 months to 14 months. Assessments were made from the end of treatment at age 15 months, at 27 months and then at 39 months of age.  Across the course of the study the families who received the video therapy showed improvement in early emerging behaviours associated with autism, compared to those who did not receive the therapy; and these improvements continued in development after the therapy-end. There was also a noticeable positive impact on parent-infant interactions. We thus demonstrate for the first time, evidence of a treatment effect on early emerging autism symptoms from infancy prodromal intervention. The study highlights the potential value of early intervention and of repeated assessments within extended follow-up.

ABSTRACT:

Background: There has been increasing interest in the potential for pre-emptive (pre-diagnostic) interventions in the infancy prodrome of autism, but little investigation as to their effect.

Objectives: To determine the longer term developmental outcomes to age 39 months of a parent-mediated video-aided intervention between 9-14 months for infants at familial risk for autism.

Methods: Two-site, two-arm assessor-blinded randomised controlled trial a 12-session therapist-delivered, parent-mediated social communication intervention delivered between 9 and 14 months of age (iBASIS-VIPP), against no intervention. iBASIS-VIPP is a modification for the autism prodrome of the Video Interaction for Promoting Positive Parenting (VIPP) programme. The home-based intervention uses video-feedback to help parents understand and adapt to their infant’s individual communication style so as to promote optimal social and communicative development. iBASIS-VIPP extended the original 6 session VIPP program by adding up to six planned booster sessions according to need in discussion with family, and added therapeutic procedures to address any emerging developmental atypicality. The sample was 54 infants (28 intervention, 26 non-intervention) at familial risk of autism but not otherwise selected by developmental difficulty. Assessments were at 9-month baseline, 15-month treatment endpoint, and 27 and 39-month follow-up. Primary outcome was the level of emergent autism-related behaviour (‘prodromal symptoms’), blind-rated on Autism Observation Schedule for Infants (AOSI) or Autism Diagnostic Observation Schedule (ADOS-2) across the four assessment points. Secondary outcomes were: blind-rated parent-child interaction (parent non-directiveness on the Manchester Assessment of Caregiver-Infant Interaction (MACI), parent synchrony on Dyadic Communication Measure for Autism (DCMA), child attentiveness on MACI and child initiations on DCMA). Other outcomes were child language (Mullen); non-blind parent-rated communication and socialisation (Vineland). Pre-specified intention to treat analysis combined estimates from repeated measures within correlated regressions to give an estimate of the overall effect of the infancy intervention. To summarize the treatment group differences in a principled fashion, the multiple point estimates were combined into an estimated area between the curves over time (sum of trapeziums, Figures 1 and 2). Trial registration: ISRCTN 87373263.

Results: Effect estimates for the autism prodromal symptoms, largest at 27 months, had confidence intervals at each separate time point including the null, but showed a significant consistent reduction when considered over time (ES=0.32; 95% CI 0.04, 0.60; p=0.026; Figure 1a). Significant overall effects through time were also seen on proximal intervention targets of parent non-directiveness/synchrony (ES=0.33; CI 0.04, 0.63; p=0.013; Figure 1c) and child attentiveness/communication initiation (ES=0.36; (95% CI 0.04, 0.68; p=0.015; Figure 1b). There was no effect on categorical diagnostic outcome, nor on other developmental or language measures (Figure 2a-d).

Conclusions: To our knowledge this is the first study of prodromal intervention for infants at risk, which has focused on emerging autism-related prodromal symptom trajectories and other dyadic treatment targets through 3 years. We demonstrate evidence of a treatment effect, extending after intervention, consisting of significant reduction in the overall level of emergent autism-related behaviours over time and enhanced parent-child dyadic social communication. The study highlights the value for early intervention trials of extended follow-up and repeated assessments within extended follow-up.

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Investigating Gender-Specific Trajectories of Autistic Traits Across Childhood and Adolescence in a Large Birth Cohort

  1. Mandy1, J. Heron2, E. Pellicano3, B. St. Pourcain4 and D. H. Skuse5, (1)University College London, London, United Kingdom, (2)School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom, (3)Centre for Research in Autism and Education (CRAE), UCL Institute of Education, University College London, London, United Kingdom, (4)University of Bristol, Bristol, UNITED KINGDOM, (5)UCL GOS Institute of Child Health, London, UNITED KINGDOM

    SUMMARY:

Based on data from a large (N=9744), longitudinal study, we discovered that a sub-group of girls show a substantial escalation of autistic characteristics during adolescence. This may partly explain why females tend to be diagnosed with autism later than males. We measured autistic social traits in the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort study, when children were aged 7,10,13 and 16 years.  For boys, these traits were stable over time, but girls showed a different pattern: between 10 and 16 years there was a marked increase in their levels of autistic social difficulties. This reflected the existence of a sub-group of girls who do not present with obvious social problems in childhood, but who subsequently showed substantial autistic difficulties once they entered their teenage years. Interestingly, this is in line with a proposal, never previously tested, made by Hans Asperger in his original 1943 paper describing ‘Autistic Pyshcopathology in Childhood’. In this work, Asperger wondered why he saw so few girls with autism, and wrote: ‘it could be that autistic traits in the female become evident only after puberty. We just do not know’. Our educational and clinical systems must be configured to be sensitive to late-onset social difficulties, especially in females. It remains to be discovered whether girls with social problems that only became overt in adolescence actually did experience subtle but meaningful autistic difficulties in childhood, which went unnoticed and unsupported.

ABSTRACT:

Background: Autism spectrum disorder (henceforth ‘autism’) is a dimensional condition, which sits at the extreme of the continuum of autistic traits (ATs) that extends throughout the general population. There is mounting evidence that autism presents differently in males and females (Lai et al., 2015). To date, almost all studies of autism sex/gender differences have been cross-sectional, with a lack of longitudinal research. Therefore, we investigated gender differences in AT trajectories across childhood and adolescence. We tested the opposing predictions of two hypotheses about the development of the female autistic phenotype:

  1. The female compensation hypothesis – females with autistic difficulties develop strategies to manage their social difficulties, such that their ATs diminish over time (e.g., Mandy et al., 2012).
  2. The adolescent emergence hypothesis – ATs in females become more overt later in development, such that their ATs escalate during adolescence (e.g., Asperger, 1943).

Current diagnostic criteria, which are largely based on male cases, are relatively insensitive to the female autism phenotype. Therefore, we included participants across the full range of AT severity, not just those with an autism diagnosis, to avoid a systematic bias against participants with female-typical autistic difficulties.

Objectives: To study gender differences in the trajectories of ATs in a large general population sample across childhood and adolescence.

Methods: Participants (N=9744) were girls (n=4784) and boys (n=4960) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort study. ATs were assessed aged 7, 10, 13 and 16 years using the Social Communication Disorders Checklist (SCDC), a widely used and psychometrically sound parent-report AT measure. These longitudinal data were modelled using latent growth curve and growth mixture models.

Results: We observed different AT trajectories for males and females (Figure 1). A latent growth curve model showed that, controlling for IQ, non-autistic psychopathology and socio-economic status: (a) aged 7, males had higher ATs than females (p<.001); (b) males and females both showed a decline in ATs between 7 and 10 years; (c) females, but not males (p<.001), showed a substantial escalation in ATs between 10 and 16 years.

This same pattern of findings occurred when we investigated gender ratios of those with very high ATs. For example, aged 7 years, males had much higher odds than females of scoring ≥ 99th AT centile (OR = 6.15, 95% CI [5.44, 6.85]), but by 16 years females and males had similar odds of having ATs ≥ 99th centile (OR=1.18, 95% CI [0.56, 1.80]).

Growth mixture modelling revealed three trajectory groups (Figure 2): Class 1 (26% female) who showed elevated ATs across childhood and adolescence; Class 2 (50% female) who showed persistently low ATs across childhood and adolescence; and Class 3 (52% female) who showed escalation of ATs during adolescence.

Conclusions: We present the first empirical evidence for the adolescent emergence hypothesis: a sub-group of girls showed substantial escalation of ATs between 10 and 16 years. This may partly explain why females tend to be diagnosed with autism later than males.

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ABOUT INSAR AND IMFAR

The International Society for Autism Research (INSAR) is a scientific and professional organization devoted to advancing knowledge about autism spectrum disorders. INSAR was formed in 2001 and is governed by an elected, volunteer Board of Directors that oversees all functions of the Society. The International Meeting for Autism Research (IMFAR) is an annual scientific meeting, convened each spring, to exchange and disseminate new scientific progress among ASD scientists and their trainees from around the world. The first and primary aim of the meeting is to promote exchange and dissemination of the latest scientific findings and to stimulate research progress in understanding the nature, causes, and treatments for ASD. Research on ASD involves sophisticated behavioral and biological approaches. ASD affects people’s functioning in virtually every domain, requiring interdisciplinary research collaboration to gain comprehensive knowledge of the disorder.

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CONTACT:
Adam Pockriss
Rubenstein
apockriss@rubenstein.com I 917.596.5951

Julia Tomkins
Rubenstein
jtomkins@rubenstein.com I 973.722.4736