Of Scaredy Cats and Cold Fish: The autonomic nervous system and behaviour in young children

markdownabstract__Abstract__ The autonomic nervous system regulates the body’s internal functions. The goal of this regulation is to maintain bodily homeostasis in a changing external environment. The autonomic nervous system acts largely independent of volition and controls heart rate, respiratory rate, digestion, and perspiration. It is divided into two partially antagonistic systems: the sympathetic nervous system and the parasympathetic or vagal nervous system. In general, the vagal system primarily regulates “rest and digest” functions. In contrast, the sympathetic nervous system can elicit the “fi ght or fl ight” response with increased arousal and energy generation in response to stress or threat. Together with the hypothalamic-pituitary adrenal (HPA) axis, the autonomic nervous system mediates the body’s response to stress. Because of this central role in stress response and the close relation of stress with the onset and recurrence of psychiatric disorders, both systems are potential biomarkers for psychiatric disorders. The current thesis investigates possible determinants of stress regulation, as well as the associations of stress regulation with emotional and behavioural symptoms very young age. The majority of the studies in this thesis were performed within the Generation R study. The Generation R Study is a large population-based prospective cohort study from fetal life onwards. It was designed to identify early environmental as well as genetic causes of abnormal growth, development and health from fetal life onwards. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. The studies presented here concern children who participated in the Focus Cohort. The Focus Cohort consists of a randomly selected subgroup of Dutch children of Caucasian origin and their parents. Studies conducted in the Focus Cohort were able to utilise more in-depth assessments. The research discussed in chapter 6 was performed within the “Beren van de Weg” study. This is a clinical, outpatient study, conducted by the departments of Child and Adolescent Psychiatry of either the Erasmus Medical Center in Rotterdam and Leiden University Medical Center— Curium. All consecutive referrals with a primary diagnosis of Generalized Anxiety Disorder, Separation Anxiety Disorder, Social Phobia or Specifi c Phobia were eligible for inclusion . In chapter 2 we examined the potential impact of maternal psychopathology on infant heart rate and heart rate variability. We showed that a maternal history of psychopathology before childbirth was associated with increased heart rate and lower vagal modulation in the infant. Similarly, postnatal maternal symptoms, especially anxiety and depression symptoms, were related to increased heart rate in the infant. Both genetic and environmental mechanisms, which are certainly not mutually exclusive, could underlie the association between maternal psychopathology and infant heart rate. In chapter 3 we assessed the putative benefi cial effect of breastfeeding on child autonomic functioning. To address the issue of residual confounding, we compared the effect of breastfeeding with that of a contrasting variable, infant fruitpuree consumption. It is related to similar environmental epiphenomena as breastfeeding. We found that infants, who were exclusively breastfed at two months of age, had lower sympathetic modulation than infants not breastfed. However, our data showed that, similar to breastfeeding, infants who ate more fruitpuree had lower sympathetic modulation as well. Association does not imply causation. In fact, in both instances the causal pathways linking the risk factors to autonomic functioning remain unclear. Moreover, in the case of breast feeding, a limited effect size with a similar order of magnitude as the effect of another, seemingly trivial dietary component, calls into question the clinical relevance of the association, 8 105 even if it contains a causal component. In chapter 4 we addressed the relation between infant autonomic functioning at 14 months and behaviour at age 18 months. We found that the association between autonomic functioning and infant externalising behaviour, was moderated by maternal psychiatric symptoms. We observed that low heart rate was associated with aggressive behaviour, only in a subgroup of children whose mothers had high psychiatric symptoms. This suggests that in the presence of maternal risk factors, low autonomic arousal renders children particularly susceptible to externalising behaviour. This lends support to the fearlessness theory, which posits that low autonomic arousal in children is an indicator of fearlessness. We hypothesize that in the presence of maternal psychopathology, with less adequate parenting and maternal guidance in coping with fearless behaviour, these children actually develop aggressive behaviour. In chapter 5 we examined the association between a child’s heart rate at 14 months and behavior at 3 years. Low heart rate was specifi cally and strongly associated with the odds of the child lying during the gift delay task as well as with low levels of anxiety. We suggest that low anxiety and a tendency to lie are indicative of low levels of emotional reactivity. Low heart rate may thus delineate a small group of children that are composed and calculating, rather than overly emotionally reactive and overtly aggressive. However, we could not demonstrate an association between heart rate and parent rated aggressive behaviour. This could be because the children in our study were considerably younger than those in earlier studies. In young children aggressive behaviour is common, but usually time limited. Proactive, planned aggression, which is commonly accompanied by low levels of emotional reactivity, develops later in life than reactive aggression. Chapter 6 details the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels in a clinical sample of 116 children and adolescents. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production and a trend towards a decreased cortisol morning rise. Persistence of an anxiety disorder may change HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders. Chapter 7 highlights the main results of the previous chapters and places them in a broader context. The main body of the chapter details the different methodological issues encountered during this research. Clinicial implications and recommendations for future research are discussed as well.