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Rising prevalence of autism
The recent Center for Disease Control or CDC report was not just alarming for the continued rapid rise in autism but also the widening difference in prevalence between males and females. While previous data indicated a ratio of 2:1 to 4:1, the current report demonstrates a rise to 5:1.
Rising tide of autism with widening gender gap is not just in the West
According to Lai and colleagues from the Department of Physical Medicine and Rehabilitation, Chia-Yi Christian Hospital, Taiwan, an analysis of registry data from 2004 to 2010 revealed that between 2004 to 2010, the registered cases between 3 and 17 years old increased from 3995 to 8072 annually. Even more importantly, the prevalence gender rate ratio ranged from 5.64:1 to 6.06:1. Autism was seen more in urban than rural areas.
No Easy Explanation for Gender Differences in autism
Gender based differences are not just limited for autism but also are seen in other neurodevelopmental dysfunctional states such as reading and learning disabilities, oppositional defiant disorder and ADHD. Females on the other hand tend to suffer more from disorders arising after puberty, e.g. psychiatric disorders like major depression and anxiety disorder, irritable bowel syndrome etc.
Why is it important to know the causes of gender based differences in autism?
Clues to potential protective factors may help identify newer therapeutic interventions and as such affect outcome.
Sex based differences in autism
- The gender differences are less marked become less significant in kids with severe cognitive dysfunction.
- Many (but not all) studies suggest that gender differences are even more remarkable in "high functioning" kids with autism.
Autism in Females
- More learning disabilities
- More problems at school
- Girls are more likely to be bullied less and blend in easier with girls without autism because of less social disabilities.
What factor/s protect girls from autism spectrum disorders?
1. Just a characteristic of certain parents each parent individually or the couple combined i.e. some parents just have boys or girls.
2. One frequently implicated factor with some evidentiary support is influence of hormones.
3. Associated factors affecting the phenotypic expression of autism related genes
4. According to the Schwarz and Bilbo and published in the journal Hormones & Behavior. 2012, sex differences in the colonization and function of glia within the normal developing brain may contribute to distinct windows of vulnerability between males and females.
Factors enhancing the possibility of missed diagnosis in females with autism
- Girls with autism tend to have similar interests as girls with autism like dolls etc. unlike boys with autism with tend to be more different than the boys with autism.
- Girls with autism have lesser repetitive behaviors and lesser irritability than their male counterparts. Hence the greater chances of missing diagnosis in girls than boys.
- Females may have superior social skills at adaptation. Higher-functioning girls with autism frequently escape diagnosis. These girls appear to have better social skills as compared to male counterparts.
- Perhaps some females with mild manifestations overcome those traits and fall below index of suspicion for diagnosis
- Girls with autism may be more shy or anxious and as such may contribute to missing the diagnosis.
Main factors determining sex ratio of a disorder like autism
- Sex ratio at conception
- Adjusted sex ratio after accounting for sex-selective loss during pregnancy
Potential factors affecting sex ratio in autism
- Differences in hormonal balance and/or maternal stress and/or maternal inflammatory state. This is consistent with high levels of intrauterine testosterone.
- High maternal intrauterine levels of testosterone are associated with autism, ADHD, and oppositional defiant disorder. Male preponderance suggests role for high maternal intrauterine androgen levels in autism.
- Whitehouse and colleagues from the Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Western Australia, AustraliaTelethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Western Australia, Australia documented that free androgen index is an independent predictor of language difficulties in girls suggesting that early life testosterone exposure is linked to pragmatic language difficulties in women.
- Recently, autism has been linked to obesity and diabetes and women with these characteristics have elevated androgen levels. Dr. James from The Galton Laboratory, Department of Genetics, Evolution and Environment, University College London, London, UK. argues that if the intrauterine androgen levels are maternal in origin and not fetus, it would explain the association of autism with various maternal disorders.
- Intestinal bacterial flora and intestinal permeability has been linked to pregnancy related problems including intrahepatic cholestasis of pregnancy and fetal loss.
- Maternal obesity appears to be a risk for autism. Gastrointestinal bacterial flora is involved in pathogenesis of infecto-obesity directly via type of gut flora and indirectly via causing a low grade inflammatory state as evident by high anti-LPS.
- Maternal diabetes has been linked to autism. Again, intestinal bacteria and intestinal permeability play a role in pathogenesis of diabetes
Autism, hormones, immune regulation and gender differences
According to Dr. Becker of National Institute on Aging, National Institutes of Health, Baltimore, MD, “Male bias in both autism and pediatric autoimmune disease is thought to involve hormonal perturbations…..These early molecular events, at a time of rapid development, are intimately linked to concurrent development in the brain and immune system. It is suggested here that these early regulatory events may overlap between autism and autoimmunity in determining male sex bias and may provide evidence of an etiological link among autism, immune dysregulation, and autoimmune disease”.
Autism as a gender defiant disorder
Bejerot and colleagues from Karolinska Institutet, Stockholm studied hormone levels in autism as compared to controls. Publishing the findings of their controlled study in the journal British Journal of Psychiatry, they described autism as a “gender defiant disorder” This was based on the fact that female subjects with autism in their study exhibited high testosterone and masculine features while males with autism demonstrated female characteristics.
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