Salivary alpha amylase diurnal pattern and stress response are associated with body mass index in low-income preschool-aged children
Introduction
The autonomic nervous system (ANS) consists of the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS). The functioning of these two complementary systems is measured primarily via indices of cardiovascular physiology (e.g., heart rate, blood pressure) or catecholamines (epinephrine and norepinephrine) (Granger et al., 2007). Salivary alpha amylase (sAA) has been described as a marker of SNS basal activity and stress reactivity (Rohleder et al., 2004, Granger et al., 2007, Nater and Rohleder, 2009), although it is debated as to whether sAA signals pure SNS activity or a combination of SNS and PNS activation (Bosch et al., 2011, Ditzen et al., 2014). It is known that SNS stimulation promotes the secretion of norepinephrine, which in turn increases sAA secretion (Kuebler et al., 2014). The result is a robust diurnal pattern for sAA, defined by a pronounced decline within the first 30 min after awakening, steadily rising in the afternoon, and peaking in the late afternoon or evening (Rohleder et al., 2004, Nater et al., 2007). sAA is sensitive to psychological stressors (Nater et al., 2006, Thoma et al., 2012), in general rising in response to stressors (Rohleder et al., 2004).sAA reactivity in response to stress correlates with stress induced serum catecholamine levels (Ditzen et al., 2014, Thoma et al., 2012) and cardiac physiological changes observed in response to stress (Nater et al., 2006, El-Sheikh et al., 2008). Associations between basal sAA output and resting SNS activity have been examined less frequently; one recent study of adult males found stronger sAA-SNS associations under challenging compared to resting conditions (Ditzen et al., 2014). Thus, although the specific nature of sAA-SNS associations has yet to be determined, particularly with regard to resting SNS-sAA associations, evidence suggests that sAA may be a reasonable marker of SNS stress reactivity or at least of SNS dominance (Nater and Rohleder, 2009). The methods used to measure SNS functioning directly are typically fairly invasive (e.g., venipuncture, heart rate, skin conductance). As sAA is measured in saliva, it is more easily used in stress research with young children (Hill-Soderlund et al., 2014).
As has been hypothesized with the hypothalamic–pituitary–adrenal axis (Gunnar and Vazquez, 2001), chronic activation of the SNS in the face of stress has been hypothesized to lead to down-regulation of the system (Lovallo, 2011, Pervanidou and Chrousos, 2012), such that chronic stress exposure is associated with low basal sAA activity and reduced sAA reactivity in response to challenge. Lower basal sAA patterns have been associated with chronic stress exposure in children (Hill-Soderlund et al., 2014, Wolf et al., 2008). Also in children, attenuated sAA reactivity in response to stress has been associated with more disruptive behavior (Granger et al., 2007, Susman et al., 2010, de Vries-Bouw et al., 2012), more anger and impulsivity (Spinrad et al., 2009), and weaker ability to delay gratification (Lisonbee et al., 2010). Both psychosocial stress exposure and these behavioral features have been associated with a higher risk of obesity in children (Lumeng et al., 2003, Seeyave et al., 2009, Lumeng et al., 2013, Leung et al., 2014). We therefore hypothesized that these blunted basal and stress–responsive sAA patterns linked with chronic stress exposure and poor emotional and behavioral regulation among children would also be associated with increased adiposity.
Studies of adults provide support for the proposed conceptual model. Of the few studies that have considered SNS responses to stress in relation to adiposity, lower SNS stress responses assessed using cardiac measures were associated with greater adiposity (Carroll et al., 2008, Jones et al., 2012). One study assessing SNS reactivity to stress via sAA also found a trend for an association between lower sAA stress response and greater adiposity (Thoma et al., 2012).
Resting SNS activity as measured by cardiac physiology is also related to obesity risk, although evidence for the direction of association is more mixed. For example, cross-sectional studies have reported associations between obesity risk indicators and greater resting SNS activity (Tentolouris et al., 2006). However, low resting SNS activity has also been implicated in weight gain (Tataranni et al., 1997) and slower weight loss over time (Astrup et al., 1995). Two studies that examined diurnal sAA and adiposity found lower diurnal sAA associated with higher body mass index (BMI; Nater et al., 2007) or no association (Veen et al., 2012).
Fewer studies have been done in children and their results are more conflicting. The only study to examine cardiac reactivity to stress in relation to adiposity was in preschool-aged children, and found a negative association (Alkon et al., 2014). In studies of older children (ages 8–14 years) assessing cardiac physiology, some have found decreased resting SNS activity in association with adiposity (Nagai et al., 2003, Vanderlei et al., 2010, Baum et al., 2013), whereas others have found increased resting SNS activity in association with adiposity (Rabbia et al., 2003, Latchman et al., 2011, Rodríguez-Colón et al., 2011, Tascilar et al., 2011, Soares-Miranda et al., 2011, Altuncu et al., 2012). Of note, none of these studies examined sAA as potential marker of resting SNS activity or stress response.
To our knowledge there are no studies of how both resting and stress–responsive SNS activity relates to adiposity during early childhood. Further, no study has considered sAA (either diurnal pattern or stress response) in relation to adiposity in young children. Low-income preschool-aged children are at high risk for obesity (Kimbro et al., 2007) and experience high levels of chronic stress (Evans and Kim, 2007). Links between physiological stress pathways and obesity may be a novel point for intervention. Yet, knowledge gaps regarding the nature of such associations must first be addressed. This study therefore sought to examine sAA diurnal pattern and sAA stress response in relation to adiposity among low-income preschool-aged children. Based on the literature showing that low SNS activity, particularly reduced reactivity to stress, is associated with greater obesity risk in adults, and considering the findings on sAA and child behavioral outcomes that have been associated with obesity risk, we hypothesized that lower sAA diurnal output and lower sAA response to stress would each be associated with greater adiposity in young children.
Section snippets
Study design and participants
Participants were children who had attended Head Start, a preschool program free to low-income families in the United States. Families were invited to participate in a study described as seeking to understand whether children with different levels of stress hormones eat differently and included a diurnal saliva sampling protocol. All children in this original study were contacted to participate in a follow-up study, which included a stress-elicitation and associated saliva sampling protocol;
Results
Mean diurnal sAA morning level (i.e., “intercept”) was 26.15 U/ml (SD = 1.90) and mean diurnal sAA slope was 0.06 (SD = 0.01), indicating that the general diurnal pattern was for children to show lower morning sAA levels that increased over the course of the day. Median reactivity sAA AUCI was 17.38 U/ml/min (range: −2407.20 to 1694.10), indicating a slight increase from baseline overall. Fig. 1 illustrates sAA responses across the protocol (stratified by weight status).
Unadjusted linear regression
Discussion
We found that lower sAA morning level (the diurnal intercept) and more rapid increase in sAA over the course of the day (the diurnal slope) were each associated with a higher BMI z-score. Being female was associated with higher BMIz in these models. Lower sAA reactivity to a stressor was associated with a higher BMI z-score. These results provide support for our conceptual model that stress physiology reflective of chronic stress exposure is associated with greater adiposity among low-income,
Role of the funding source
Funding for this research was provided by the National Institutes of Health, grant numbers NIH 1RC1DK086376, NIH 1R21DK090718 and the American Heart Association Midwest Affiliate Grant-in-Aid grant number 10GRNT4460043.
Conflict of interest
The authors have no conflicts of interest to disclose.
Acknowledgements
We thank the families who participated in the study, research assistants who collected the data, and our Head Start agency partners.
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