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Author for correspondence: Carolyn E. Cesta, E-mail: [email protected]
Introduction
Prenatal androgen exposure has been hypothesized to be associated with the development of neuropsychiatric disorders including autism spectrum disorders (ASD) (Baron-Cohen et al., 2011), attention-deficit/hyperactivity disorder (ADHD) (de Bruin et al., 2006; Baron-Cohen et al., 2011), and Tourette's disorder and chronic tic disorders (TD/CTD) (Peterson et al., 1992; Alexander and Peterson, 2004; Martino et al., 2013). Additionally, some psychiatric disorders show a response to treatment with anti-androgens, such as TD/CTD (Peterson et al., 1994, 1998), potentially implicating altered androgenic pathways in their etiology.
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004). The most prominent feature of PCOS is hyperandrogenism, characterized by elevated testosterone levels in serum and an increased testosterone to sex hormone-binding globulin ratio, which persists throughout a woman's reproductive years (Goodarzi et al., 2011). Previous studies have reported significantly higher levels of androgens throughout the pregnancies of women with PCOS, compared with pregnancies of women without PCOS (Sir-Petermann et al., 2002; Anderson et al., 2010; Barry et al., 2010; Maliqueo et al., 2013).
Studies have therefore utilized maternal PCOS as a model of offspring exposure to elevated levels of prenatal androgens, reporting that the children of women with PCOS are at increased risk of both ASD and ADHD (Palomba et al., 2012; Kosidou et al., 2016, 2017; Cherskov et al., 2018).
However, women with PCOS themselves have an elevated prevalence of a range of psychiatric disorders compared with women without PCOS, including ASD and ADHD (Ingudomnukul et al., 2007; Herguner et al., 2015; Cesta et al., 2016; Cherskov et al., 2018). Because these disorders are moderate to highly heritable (Posthuma and Polderman, 2013; Mataix-Cols et al., 2015), it is possible that the association between maternal PCOS and offspring neuropsychiatric disorders is confounded by shared genetic influences. Furthermore, some familial environmental factors associated with having received a diagnosis of maternal PCOS (e.g. access to health care, healthcare seeking behavior) may also influence whether the child receives a neuropsychiatric diagnosis and therefore may confound the association. Hence, further investigation is needed to disaggregate...