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Summary of Advances Cover 2016

Summary of Advances

In Autism Spectrum Disorder Research


Question 3: What Caused This to Happen and Can It Be Prevented?

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study
Eriksson JM, Lundström S, Lichtenstein P, Bejerot S, Eriksson E. Mol Autism. 2016 Jan 19;7:8. [PMID: 26793297]

There is a higher prevalence of ASD and attention-deficit/hyperactivity disorder (ADHD) in males than females. There is evidence of significant heritability in both ASD and ADHD, but there are also thought to be significant environmental factors involved in risk of diagnosis. For instance, past research suggests that exposure to high levels of testosterone in the womb may increase the risk for development of ASD and ADHD. Therefore, this study sought to better understand whether testosterone produced from a male twin fetus could lead to increased exposure to testosterone by the cotwin, theoretically increasing the other twin’s risk for ASD or ADHD.

To investigate the role of exposure to elevated prenatal testosterone levels in the risk for ASD or ADHD, the researchers assessed ASD and ADHD traits in fraternal female-female, female-male, and male-male twin-paired children to determine whether the presence of a male co-twin increased the likelihood of development of ASD and ADHD. The researchers used data from the Child and Adolescent Twin Study in Sweden (CATSS). The population consisted of 4,219 male-female, 1,808 female-female, and 2,129 male-male twin pairs at either 9 or 12 years old. They assessed ASD and ADHD traits using the Autism-Tics, AD/HD, and other Comorbidities inventory (A-TAC), which is a parent interview conducted by telephone. The A-TAC tests for many traits related to ASD and ADHD, such as language, social interaction, behavioral flexibility, impulsiveness/activity, and concentration/attention.

In contrast to the hypothesis that having a male co-twin would increase the likelihood of developing ASD and ADHD, twins with a female co-twin actually had higher scores on the A-TAC, reflecting a greater number of ASD and ADHD traits than twins with a male co-twin. When breaking down the scores by trait, the scores were higher in twins with a female co-twin in attention/concentration for ADHD, and in flexibility in thought, social interaction, and abnormal sensory reactivity for ASD.

One interpretation of these results is that there may be an in utero protective effect for girls with a male co-twin. However, it is important to also consider reporting biases when interpreting these results. Since the scores were based on parent interviews, there may be underreporting of ASD and ADHD traits in female twins due to commonly existing differences between male-female twin pairs. However, the finding that having a female co-twin slightly increases the risk of displaying ASD and ADHD traits challenges our current understanding of these disorders.

Risk of psychiatric and neurodevelopmental disorders among siblings of probands with autism spectrum disorders
Jokiranta-Olkoniemi E, Cheslack-Postava K, Sucksdorff D, Suominen A, Gyllenberg D, Chudal R, Leivonen S, Gissler M, Brown AS, Sourander A. JAMA Psychiatry. 2016 Jun 1;73(6):622-9. [PMID: 27145529]

Research has shown that there is a “clustering” effect of diagnoses within families that have a child with ASD. For instance, a child with ASD is at greater risk for a co-existing psychiatric diagnosis such as schizophrenia, bipolar disorder, anxiety, and affective disorders, as well as other diagnoses such as intellectual disability or pervasive developmental disorder. Research has also shown increased risk of ASD in children whose parents have a psychiatric diagnosis. However, there had been no previous study comprehensively investigating the relationship between a diagnosis of ASD in one child and a sibling’s diagnosis of a psychiatric or other neurodevelopmental disorder.

In this study, researchers used data from three Finnish nationwide registers (the Finnish Hospital Discharge Register, the Finnish Medical Birth Register, and the Finnish Population Register Centre) to determine the rates of psychiatric and neurodevelopmental disorders among individuals who have a sibling with ASD. They looked at data from two groups: 1) 3,578 children with ASD and their 6,022 siblings and 2) 11,775 typically developing children and their 22,127 siblings.

The researchers found that 36.9% of children with ASD had at least one sibling who had been diagnosed with at least one neurodevelopmental or psychiatric disorder, as compared to only 17.4% of typically developing children. This association was strongest for childhood-onset disorders, with 29.7% of children with ASD having a sibling with at least one childhood-onset disorder, as compared to 11.6% of typically developing children. The most common childhood-onset disorders in siblings of children with ASD were ASD (10.5% versus 1.1% of typically developing children), learning and coordination disorders (15.7% versus 5.9%), attention-deficit/hyperactivity disorder (5.3% versus 1.5%), and conduct and oppositional disorders (5.0% versus 1.9%). Of the children diagnosed with a disorder, siblings of children with ASD were in general more likely to be diagnosed with a neurodevelopmental or psychiatric disorder at a younger age than siblings of typically developing children. There was no difference in this increased risk between male and female siblings.

These results show that a sibling of a child with ASD is more likely to be diagnosed with a psychiatric or neurodevelopmental disorder than a sibling of a typically developing child. One interpretation is that parents of a child with ASD may be more aware of signs and symptoms of these disorders. They may also be more likely to seek help for their other children, and seek it earlier, than parents without experience with ASD.

These results also suggest there may be a significant hereditary component to ASD, psychiatric, and neurodevelopmental disorders. However, there may also be shared environmental risk factors such as psychological stress within the family due to the challenges associated with ASD. Professionals who work with families of children with ASD should be aware of this increased risk and educate towards earlier diagnosis and intervention.

Association between influenza infection and vaccination during pregnancy and risk of autism spectrum disorder
Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, Croen LA. JAMA Pediatr. 2017 Jan 2;171(1):e163609. [Available online November 28, 2016] [PMID: 27893896]

Maternal infection and fever during pregnancy activates an immune system response that may be associated with complications or abnormalities in offspring, such as preterm birth and low birth weight. Accordingly, pregnant women are encouraged to get vaccinated against influenza, a common infection, to decrease the risk of these complications. Despite numerous investigations of maternal infection and ASD, there has been no conclusive evidence of an association. However, no studies had been previously conducted on maternal influenza vaccination during pregnancy and risk for ASD.

The goal of this study was to better understand whether or not there is a relationship between maternal influenza vaccination and development of ASD. The population for the study was 196,929 children born at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, from a gestational age of at least 24 weeks to a follow-up time between 2 and 15 years of age. Data on maternal vaccination, maternal influenza infection, and pediatric ASD diagnoses were obtained from electronic medical records. The researchers accounted for confounding variables (variables that researchers are unable to control) such as gestational age, maternal age, maternal prepregnancy body mass index, maternal race/ethnicity, and other maternal health conditions. Four time periods were investigated: first trimester, second trimester, third trimester, and anytime in the pregnancy.

The researchers found no association between risk of ASD and maternal influenza vaccination or maternal influenza infection across the entire pregnancy. When considering each trimester separately, there was a weak association between maternal influenza vaccination during the first trimester and ASD risk—a finding likely due to chance, but potentially warranting future study. Since this study found no significant increased risk of ASD with influenza vaccination, the researchers suggest that no changes to influenza vaccination recommendations should be made at this time.

Question 3

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