Article

Mill J, Petronis A. Pre- and peri-natal environmental risks for attention-deficit hyperactivity disorder (ADHD): the potential role of epigenetic processes in mediating susceptibility. J Child Psychol Psychiatry 49: 1020-1030

Institute of Psychiatry, SGDP Research Centre, London, UK.
Journal of Child Psychology and Psychiatry (Impact Factor: 6.46). 06/2008; 49(10):1020-30. DOI: 10.1111/j.1469-7610.2008.01909.x
Source: PubMed

ABSTRACT

Attention-deficit hyperactivity disorder (ADHD) is a common childhood neurobehavioural disorder defined by symptoms of developmentally inappropriate inattention, impulsivity and hyperactivity. As is the norm for most psychiatric phenotypes, traditional aetiological studies have focused primarily on the interplay between genetic and environmental factors. It is likely that epigenetic factors, i.e., heritable, but reversible changes to genomic function that are independent of DNA sequence, are also important. It is known that epigenetic processes can be induced following exposure to a range of external factors, and thus provide a mechanism by which the environment can lead to long-term alterations in phenotype. In this article we hypothesise that epigenetic dysregulation may mediate the association observed between early-development environmental insults and ADHD. We propose that understanding the epigenetic processes involved in linking specific environmental pathogens to an increased risk for ADHD may offer new possibilities for preventative and therapeutic intervention.

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    • "Prenatal ischemia-hypoxia is a common element to multiple early risk factors for ADHD including maternal smoking [Bush et al., 2000] and maternal alcohol use during pregnancy [Bosco and Diaz, 2012] as well as ischemia-hypoxia related obstetric complications [Pineda et al., 2007; Rennie et al., 2007; Getahun et al., 2013]. Consistent with the Developmental Origins of Health and Disease (DOHaD) framework [Gluckman et al., 2004; Mill et al., 2008; Swanson and Wadhwa, 2008; Swanson et al., 2009; Wadhwa et al., 2009], the association between lower birth weight and ADHD may arise from prenatal ischemia-hypoxia. Prenatal ischemia-hypoxia may directly disrupt or delay development or lead to structural or functional adaptations to the adverse intrauterine environment. "
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    • "We also found effects of neonatal complications on toddler withdrawal, emotional reactivity, and somatic complaints (as well as internalizing problems more broadly), above and beyond genetic risk. In the literature, neonatal complications are more often examined in relation to externalizing problems, ADHD in particular (Ben Amor et al., 2005; Mill & Petronis, 2008). Our findings suggest that neonatal complications may also be important for the development of internalizing problems. "
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    • "The cerebellum may be particularly vulnerable to effects of prenatal adversity, as its development begins early in intrauterine life and is markedly protracted (Limperopoulos et al., 2005; Ten Donkelaar et al., 2003; Tiemeier et al., 2010). One measure often used as a proxy for intrauterine conditions is birth weight (Mill and Petronis, 2008). The association of low and very low birth weight (defined as a birth weight b 2500 and b 1500 g respectively) with atypical cognitive and behavioral development is well established (Aarnoudse-Moens et al., 2009; Mick et al., 2002; Nigg and Breslau, 2007; Rice et al., 2007), with a number of neuroimaging studies showing changes in cerebellum in children born with (very) low birth weight (Limperopoulos et al., 2005; Lowe et al., 2011; Parker et al., 2008; Peterson et al., 2000; Shah et al., 2006; Srinivasan et al., 2006; Taylor et al., 2011). "
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