Developmental brain alterations in 17 year old boys are related to antenatal maternal anxiety
Introduction
Accumulating evidence indicates that the cognitive development of a child is related to the level of anxiety or stress experienced by its mother during pregnancy (e.g., Brouwers et al., 2001, Laplante et al., 2004, Bergman et al., 2007). However, most studies used the Bailey Scales of Infant Development or school results to assess cognitive abilities. As such research on the effects of antenatal maternal anxiety on specific cognitive functions is scarce. In a prospective longitudinal study our group showed that 15 and 17 year old adolescents born to mothers reporting high levels of state anxiety during weeks 12–22 of their pregnancy had long-term impairments in endogenous control of their performance on challenging cognitive tasks (Van den Bergh et al., 2005, Van den Bergh et al., 2006, Mennes et al., 2006). Endogenous cognitive control refers to the ability to generate triggers from within oneself or endogenously in order to control actions, strategies and thoughts interfering with optimal task performance (Miller, 2000, Miller and Cohen, 2001, Brass and von Cramon, 2004). It is opposed to exogenous cognitive control where cognitive control is triggered by external signals (e.g., a sound). Other cognitive functions associated with prefrontal functioning, such as working memory and attentional orienting, were not related to antenatal maternal anxiety (Van den Bergh et al., 2005, Mennes et al., 2006, Gutteling et al., 2006).
Based on these results orbitofrontal cortex was hypothesized as the area of the brain most influenced by antenatal maternal anxiety (Mennes et al., 2006). However, although inferences about the underlying brain functionality can be made based on the behavioral neurocognitive measures used in our previous studies, we did not measure actual brain functioning. Therefore, the purpose of the present study was to strengthen our previous finding of an impairment in endogenous control in adolescents of mothers reporting high levels of anxiety during the first weeks of pregnancy by monitoring the adolescents’ electrical brain activity with event-related potentials (ERP).
Physiological measures, such as ERPs, are more closely related to underlying biological processes compared to complex behavioral measures. The use of physiological measures can provide an important impetus for research into the mechanisms of the relationship between antenatal maternal anxiety and later development. In primates for instance, dopamine receptors, that are also linked to the development of ADHD (Durston and Konrad, 2007), were found to be influenced by the level of antenatal maternal anxiety (Schneider et al., 2008). Although some studies on antenatal maternal anxiety in humans have investigated physiology by looking at the relationship between antenatal anxiety and hormones such as cortisol (O’Connor et al., 2005, Van den Bergh et al., 2008), evidence on actual brain functioning is lacking.
Here, in light of our previous results, we contrasted ERPs measured during an exogenous control task to those measured in an endogenous control task. Exogenous control is commonly assessed with tasks such as the Stop-task or Go/Nogo (Rubia et al., 2001, Nieuwenhuis et al., 2003, Liotti et al., 2007, Nigg et al., 2008). In the Stop-task an external stimulus should trigger response inhibition, and in a Go/Nogo task, which we used here, the stimuli clearly indicate which response should be given. Endogenous cognitive control on the other hand, can be assessed using different paradigms. For instance task-switching and dual task paradigms are often used (Gehring et al., 2003, Wylie et al., 2003). Here we assessed endogenous control using a newly developed gambling paradigm (Mennes et al., 2008).
Section snippets
Subjects
Twenty-three boys were included in the current study. They were a subgroup of the adolescents of our longitudinal study that participated in the behavioral cognitive assessment at age 17 (n = 49; Mennes et al., 2006). Only boys were included since our previous results yielded more consistent results in boys. This might be due to the fact that the assessed cognitive functions are more likely to be associated with antenatal maternal anxiety in boys, compared to a higher chance for mood-related
Go/Nogo
There was no effect of the level of antenatal maternal anxiety on the mean reaction time, the standard deviation of the reaction time, or the number of correct responses measured in this task.
Gambling
The level of anxiety measured during pregnancy was associated with the distribution of gamble/inhibition responses across trials (Fig. 1). This distribution was quantified in a contrast measure defined as (M − S)/(S + M) where S is the proportion of gambles in trials with a gain ⩽ the reward for an inhibition
Discussion
The results presented here suggest that the brain activity of adolescents is related to the level of anxiety experienced by their mother during weeks 12–22 of pregnancy. These effects were present in a gambling paradigm, but not in a Go/Nogo paradigm indicating a specific vulnerability of the development of endogenous cognitive control. The dissociation in the effect of antenatal maternal anxiety on exogenous vs. endogenous cognitive control was evident both in performance and brain activity.
Acknowledgements
The authors thank all adolescents and parents for participating, and Heidi Wouters and Jan Vervisch for help with the ERP acquisition. Supported by the Research Foundation Flanders (FWO) (#G.0211.03) and by the K.U.Leuven (IMPH/06/GHW). L.L. is holder of the UCB Chair on Cognitive Dysfunctions in Childhood at the K.U.Leuven.
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Present address: Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, NYU Child Study Center, 215 Lexington Ave., 14th Floor, New York, NY 10016, USA.