Prenatal Risk Factors and the Etiology of ADHD—Review of Existing Evidence

Abstract

While it is well accepted that attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder, not all of the risk is genetic. It is estimated that between 10 and 40% of the variance associated with ADHD is likely to be accounted for by environmental factors. There is considerable interest in the role that the prenatal environment might play in the development of ADHD with previous reviews concluding that despite demonstration of associations between prenatal risk factors (e.g. prematurity, maternal smoking during pregnancy) and ADHD, there remains insufficient evidence to support a definite causal relationship. This article provides an update of research investigating the relationship between prenatal risk factors and ADHD published over the past 3 years. Recently, several epidemiological and data linkage studies have made substantial contributions to our understanding of this relationship. In particular, these studies have started to account for some of the genetic and familial confounds that, when taken into account, throw several established findings into doubt. None of the proposed prenatal risk factors can be confirmed as causal for ADHD, and the stronger the study design, the less likely it is to support an association. We need a new benchmark for studies investigating the etiology of ADHD whereby there is an expectation not only that data will be collected prospectively but also that the design allows the broad range of genetic and familial factors to be accounted for.

Smoking, psychiatric illness and the brain

“…1 Rates of smoking are markedly higher among people with psychiatric illness than in the general population, estimated at being 2-5 times higher in patients with several disorders, including schizophrenia, mood disorders, anxiety disorders, attentiondeficit/hyperactivity disorder (ADHD), binge eating disorder, bulimia and substance use disorders. [2][3][4][5] The aim of this editorial is to emphasize the importance of smoking as a factor that should regularly be considered as a potential confound in neurobiological studies of psychiatric illnesses. Smoking can be regarded as playing at least several roles in relation to psychiatric illness -as a causal factor contributing to psychiatric disorders, as an agent causing brain changes on its own that may interact with psychiatric pathophysiology, or as a modulator of effects of psychotropic medications.…”

“…In the case of ADHD, a large body of evidence supports an association between maternal smoking during pregnancy and increased risk for ADHD. 5 However, whether maternal smoking is actually a causal factor for ADHD remains open to question, with recent research suggesting that the association may be due to a shared familial/genetic susceptibility for both smoking and ADHD. 5 Nonetheless, children with ADHD born from mothers who smoked during pregnancy have been reported to have more severe behavioural problems than children with ADHD born from nonsmoking mothers, with a dose-response relationship between the amount smoked and several cognitive and clinical variables in the children.…”

“…5 However, whether maternal smoking is actually a causal factor for ADHD remains open to question, with recent research suggesting that the association may be due to a shared familial/genetic susceptibility for both smoking and ADHD. 5 Nonetheless, children with ADHD born from mothers who smoked during pregnancy have been reported to have more severe behavioural problems than children with ADHD born from nonsmoking mothers, with a dose-response relationship between the amount smoked and several cognitive and clinical variables in the children. 6 At a neurobiological level maternal smoking during pregnancy has been shown to be associated with grey matter loss and cortical thinning 7 as well as functional alteration in neural circuitry involved in inhibitory control and reward 8,9 in children.…”

Attention‐Deficit Hyperactivity Disorder: Clinical Considerations for Women

“…A number of studies have identified that prenatal exposure to substances, including alcohol and nicotine, may increase the risk for ADHD . Yet findings from these prenatal risk studies appear to be confounded by genetic, familial, and methodologic factors . Recently, Sujan and colleagues addressed many of the methodologic problems in previous prenatal studies and investigated maternal first‐trimester self‐reported antidepressant use among a very large sample of offspring (N = 1,580,629 offspring) born to 943,776 women exposed and unexposed to antidepressants.…”

“…47,48 Yet findings from these prenatal risk studies appear to be confounded by genetic, familial, and methodologic factors. 49 Recently, Sujan and colleagues 50 addressed many of the methodologic problems in previous prenatal studies and investigated maternal first-trimester selfreported antidepressant use among a very large sample of offspring (N = 1,580,629 offspring) born to 943,776 women exposed and unexposed to antidepressants. Results revealed that in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth but not with ADHD.…”