Elevated fetal steroidogenic activity in autism

Baron‐Cohen, Simon; Auyeung, Bonnie; Nørgaard‐Pedersen, Bent; Hougaard, David M.; Abdallah, Morsi; Melgaard, Lars; Cohen, Arieh; Chakrabarti, Bhismadev; Ruta, Liliana; Lombardo, Michael

doi:10.1038/mp.2014.48

Cited by 403 publications

(395 citation statements)

References 48 publications

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“…This may impact adversely on the development of fetal organ systems, including the brain. It is notable that elevated levels of steroid hormones were recently found in the amniotic fluid of male babies who later developed autism, although whether the steroids were of maternal or fetal origin is unclear at present [83]. Sex-specific differences in placental 11-bHSD2 activity have been reported [84], and may potentially explain the increased risk of disorders, including autism, arising from developmental programming in males following adverse intrauterine experiences.…”

Section: The Placenta As a Selective Barriermentioning

confidence: 99%

The placenta: a multifaceted, transient organ

Burton

Fowden

2015

Phil. Trans. R. Soc. B

568

380

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The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain.

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Section: The Placenta As a Selective Barriermentioning

confidence: 99%

The placenta: a multifaceted, transient organ

Burton

Fowden

2015

Phil. Trans. R. Soc. B

568

380

View full text Add to dashboard Cite

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“…Some environmental factors may also contribute to the female protective effect [23]. Inuterine exposure to SSRIs [34] and steroids including progesterone and testosterone [35] are associated with greater autism likelihood amongst male children than female. Some evidence suggests higher maternal age at conception may increase likelihood of autism amongst males, but not females [36].…”

Section: Female Protective Effectmentioning

confidence: 99%

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Hull

Mandy

2017

Future Neurol.

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Autism Spectrum Disorder (ASD) has historically been diagnosed more frequently in males than females. One explanation for this is the 'female protective effect': that there is something inherent in being female that makes girls and women less susceptible to ASD.Another possibility is that ASD is under-diagnosed in girls and women, due to the existence of a 'female autism phenotype', which is not well captured by current, male-biased diagnostic criteria. To evaluate the 'female protective effect' and 'female autism phenotype' hypotheses, this narrative review describes recent developments exploring the genetic underpinning and behavioural expression of ASD in females. We then look at ways to better identify females with ASD who may be missed under the current diagnostic criteria. KeywordsAutism, Autism Spectrum Disorders, Gender Differences, Sex Differences, Genetics, Diagnosis, Person-Environment Fit IntroductionAutism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions characterised by deficits in social communication and reciprocity, and by restricted and repetitive interests and behaviours 1 . ASD is the current term used to integrate the previously separate diagnostic categories of autistic disorder, Asperger's disorder, childhood disintegrative disorder and pervasive developmental disorder -not otherwise specified (aka 'atypical autism' [2]). ASD is a lifelong condition that is present from birth. Although adult diagnosis is possible, symptoms must be reported as present from early developmental stages in order for the 1 In line with preferences from a majority of the autism community [1], we use identity-first language (e.g. 'autistic person') to refer to individuals with an ASD throughout this paper, while recognising that others might prefer person-first language (e.g. 'person with autism'). Gender differences in diagnosisASD affects approximately one to two per cent of the population [3,4], and is much more likely to be diagnosed in males than in females. Gender ratios in diagnosis vary depending on the country, cohort, and characteristics of those included, but average ratios are reported at around four males for every one female [3][4][5]. However, when looking at those individuals with intellectual disability, the male-to-female ratio narrows significantly to around two-toone [6]. In addition, population-based studies, which screen all participants in order to identify cases regardless of whether they have already been diagnosed by local services, suggest that the male-to-female ratio is closer to 3:1 [7,8]. This is in contrast to the average of around 4-5:1 generally reported in studies based on clinically-diagnosed cases [9]. The fact that a lower proportion of females are found in clinical samples than in community-based, epidemiological samples suggests that there is a bias against autistic girls and women coming to clinical attention. This bias may have existed from the very first conceptions of ASD; only 3 of 11 children in Kanner's original cases were female, and no gi...

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“…Estradiol effects on stress responses varies in pre-vs post-menopausal women (Dumas et al, 2012;Albert et al, 2015). (g) Females are at greater risk of dementia and adverse effects of many pharmacologic agents used in the treatment of adult disorders (Parekh et al, 2011;Franconi et al, 2012;Spoletini et al, 2012). brain (Chura et al, 2010;Baron-Cohen et al, 2015). Programming of important regulatory brain regions, including the neuroendocrine hypothalamus, via such steroid hormone effects on cell migration patterns during early development likely also contributes to sex differences in how the individual responds to environmental perturbations throughout life .…”

Section: Sex Differences Related To Sex Chromosomes and Hormones And mentioning

confidence: 99%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

124

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The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

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Elevated fetal steroidogenic activity in autism

Cited by 403 publications

References 48 publications

The placenta: a multifaceted, transient organ

The placenta: a multifaceted, transient organ

Protective Effect or Missed Diagnosis? Females with Autism Spectrum Disorder

Sex as a Biological Variable: Who, What, When, Why, and How

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