Autism

• Durkin et al (2017) 


  There is an increasing prevalence of autism diagnoses being made in all socioeconomic groups. There are around 1.3 million children diagnosed by age 8.
• Autism diagnoses conditions: 


  Diagnosed using both social and non-social criteria (with a degree of difficulty). Need both social and non-social criteria and therefore level of support is varied.
• Lai et al (2014) 


  Autism is co-occuring with epilepsy (15%), learning difficulties (25%), self-harm (50%), dyspraxia (50%) depression and anxiety (50%), language delays (50%) among others.
• Sandin et al (2014) 


  (Scandinavian study)

  The more genetically similar you are to a person diagnosed with autism, the increasingly likelihood of autism.
• Fu et al (2022)

  Genes associated with autism are common in autistic individuals, and there are 72 of them. (_<0.001).
• Chen et al (2017):

  NRXNs: what do they do and how do they affect autism? 


  NRXNs are cell adhesion molecules which connect neurones and mediate signally across the neuronal junction. AKA they bund to NLGNS to make a bridge so that neuronal information can pass to postsynaptic neurone.

  10% of people with NRXN1 mutations have autism, 50% have epilepsy and 80% have speech delays.
• Satterstorm et al (2019): PTVs and autism: 


  PTVs (Protein-trunicating variants) are genetic variants which shorten coding sequences of genes.

  Found to be much higher in those with just one or both of ADHD and autism compared to controls.
• Grove (2018) 


  There are 5 common genetic variants associated with autism and are on 4 different chromosomes.

  Autism has a significant association between autism and increased cognition (e.g., higher IQ, educational attainment, likelihood of a college degree etc.
• Modabbernia et al (2017)


  Environmental risk factors for autism include:

  • Maternal BMI at 18 years old.
  • Parental age.
  • Hormonal factors
  • Gestational diabetes
  • Birth complications
  • Sex
• Lyall et al (2011) 


  Higher the mother's BMI at 18 years old, the increased likelihood they will have a child with autism.
• Cross-disorder group of the psychiatric genomics consortium (2019):


  Looked at 8 psychiatric conditions and found there are 109 common genetic variants associated with them. Found that Autism Spectrum disorder, ADHD and Tourettes all had substantial genetic correlation and clustering.
• Sandin et al (2015): 


  The higher the paternal age, the increased likelihood of autism in the child. This is because sperm cells undergoing meiosis and copying DNA have an increased likelihood of genetic mutation.

  Effect not seen in mothers.
• Taylor et al (2019): 


  Found that as paternal age increases, there is an increases risk of 5 conditions including ASD- but there's overlap between them.

  However when you look epidemiologically, you find that in only schizophrenia and ASHS do you see a sizeable difference between likelihood of autism in the child. Suggesting it's likely not that increased paternal age increases gene mutations, which increases autism likelihood but instead fathers with autism find a partner or have children at later ages- who pass on genes to their children.
• "The Masculinisation programming window"-> how does it relate to autism?


  Theory is that autism is more common in boys because they will have increased levels of testosterone in amniotic sac compared to girls. As testosterone plays a role in neurone division in the brain) this is what causes brain differences and structural differences in autistic people.
• "The Masculinisation programming window"


  A period at 12-19 weeks (2nd trimester) of pregnancy which there is increased testosterone in amniotic sac. Testosterone acts as a transcription factor and depending on which genes it 'turns on or off' can result in altered gene expression
• Rotem et al (2021)

  Across all 4 countries (Finland, Israel, Sweden and UK) there was an increased autism likelihood in the child if mother had PCOS (which is a hyper-androgen condition).
• Auyeung et al (2009)


  Higher levels of testosterone in amniotic sac (accessed by amniocentesis) had a significant association between testosterone and autistic traits regardless of sex.
• Hougaard et al (2015)


  Measured foetal sterioidogenic activity by pricking heels immediately after birth. Found that males had more testosterone than females, bit there was significant elevation in foetal testosterone in autistic group compared to males and females.

  Also found there was less prenatal estradiol in autistic group compared to controls.
• Mediator 


  Process through which variables are related.
• Moderator 


  Affects strength and direction of the relationship.
• Russel et al (2021)

  Autism diagnoses have increased exponentially from baseline. In 2000, ~180% above baseline but in 2020 this was ~790% above baseline. Female diagnoses are ~1400% above baseline, compared to males ~500%. Age group with the highest increase is above 19 whose increase is ~1400%.
• Havadhl et al (2021)


  Most of autism liability consists of common genetic variants, which are common in autistic people without intellectual diasabilities. In autistic people with intellectual disabilities, the rare genetic variants are more common.
• Taylor et al (2020)


  There is currently no evidence that environmental factors e.g., non shared environmental traits are contributing to the increase in autism and in people with broad ASD (have traits but not enough for a diagnosis). However genetic and environmental traits are increasing over cohorts.
• Roman-Urrestarazu et al (2022)


  Most likely age of diagnosis is 1-3 years old, and where the community is less ethnically diverse, the likelihood of diagnosis increases, deprivation also increases likelihood of diagnosis.
• Riglin et al (2021)


  SCDC (measure of developmental disorders) scores decrease over time, in both low-trajectory class and declining trajectory class, but the late emerging class scores increase over time- this group is common in girls.
• Schlaag et al (2022)

  ASD polygenic scores are associated with low prosociality in early childhood.
• Szatmari et al (2015)


  ADOS scores (measure of determining how much autism affects a person's life) were highest in the group that was moderately functioning and stable, the lowest were the functioning and improving group in the sample that was more severe and stable. However in the sample that was less severe and improving, the group that scored the lowest was lower functioning and worsening sample, and the highest scores were the moderate and stable functioning group.
• Warrier et al (2022)

  People with high-impact de novo variants exhibit higher autism polygenic scores and are more likely to have co-occurring developmental disabilities and delays, suggesting that these variants contribute to a higher genetic predisposition to both autism and other developmental issues.
• Warrier et al (2022): Walking and talking


  Autistic individuals (even when not DD gene carriers) walk and talk later than their non-autistic peers.
• Greenberg et al (2018)

  Sensory Autism Quotient scores are the only category which autistic women score higher than controls and autistic males.
• Martini et al (2022)

  Autistic women are MUCH more likely to have much higher rates of psychopathology compared to controls and autistic males. In particular anxiety, depression, self harm, and sleep disorders are the most common
• Warrier et al (2020): Gender queer people: 


  Trans people tend to have elevated autistic traits- even without diagnosis.
• Motron et al (2020) 


  Despite autism prevalence increasing over time, traits such as theory of mind, planning and cognitive flexibility are decreasing over time, between autistic and non-autistic individuals.

  Autistic children reach developmental milestone later than non-autistic children.
• Eisenberg and Lennon (1983) 


  Females are more empathetic than males in self-report but there are no evident differences when measured in other ways including physiologically.
• Joel et al (2015)

  There are some differences between the male and female brain, e.g., male brain is bigger, BUT there are more similarities than differences.
• Where are the main places gendered notions of autism come from?

  Asperger only studied males and believed autism didn't affect girls. Kanner (1943) did look at girls (had a sample of 8 boys and 3 girls) and did note differences e.g., noted they came to the clinic later but never followed them up. Kanner's initial descriptions also only focused on the boys he first observed which biased our understanding of autism.
• Loomes et al (2017)

  When relying on current diagnosis the sex ratio is 4.2:1 (m:f). But when looking at general population (and finding people not diagnosed) the ratio is 3.2:1.
• Rutherford et al (2016)


  The gender ratio of autism diagnosis depends on the instrument of assessment and between 0-9 years old the ratio is 5:1 but drops to 2:1 at 10-18 years old.
• Robinson et al (2014): Carter effect 


  Females are less susceptible to autism because they need more of autism's causes to be diagnosed.
• Iossifov et al (2014)

  The genetic composition required for an autistic child to be diagnosed is ~25% in all cases of autism, but in women it's ~45%, therefore women need a higher genetic burden to be diagnosed.