Elsevier

Psychoneuroendocrinology

Volume 98, December 2018, Pages 153-160
Psychoneuroendocrinology

Stress and immune biomarkers interact with parenting behavior to shape anxiety symptoms in trauma-exposed youth

https://doi.org/10.1016/j.psyneuen.2018.08.016Get rights and content

Highlights

  • Adolescents exposed to chronic early trauma exhibit more anxiety symptoms compared to controls.

  • Exposed mothers and youth have higher cortisol (CT) and secretory Immunoglobulin-A (s-IgA).

  • CT and s-IgA are associated with adolescents' anxiety symptoms.

  • Trauma-exposed mothers are less supportive and youth show less collaboration during a joint task.

  • CT, s-IgA, and social behavior chart independent mediating paths from trauma to anxiety symptoms.

Abstract

The relations between stress, HPA-axis, and the immune system have been extensively studied; however, no study to date addressed the joint contribution of immune and HPA biomarkers to the development of anxiety in youth exposed to chronic trauma as mediated by mother-child interaction patterns. A unique cohort of war-exposed children and their mothers, compared to matched controls, were followed from infancy and the current study reports findings from early adolescence (mean age = 11.66, SD = 1.23; N = 111; exposed = 58 control = 53). Youth and mothers' salivary cortisol (CT) and secretory immunoglobulin (s-IgA) levels were measured three times during a 4-hour lab visit, mother-child interaction patterns were quantified from a joint task, and children's anxiety symptoms diagnosed. Trauma-exposed children had higher levels of CT and s-IgA, exhibited more anxiety symptoms, and showed lower social collaboration with mother during the joint task. Trauma-exposed mothers had higher CT and s-IgA levels and showed less supportive parenting during mother-child interaction. Structural equation modeling defined three bio-behavioral paths by which trauma increases anxiety in youth. While the first path charted a behavioral link from exposure to child anxiety via diminished maternal support, the other two paths described mediated biological paths, one through HPA-axis functioning, the other via the immune system. Paths via the child's HPA and immune system were mediated by the parallel maternal variable. Findings are the first to describe the complex bio-behavioral interplay of stress and immune biomarkers and parenting behavior in shaping to the development of risk and resilience trajectories in youth growing up amidst chronic trauma.

Introduction

The relations between stress and the immune system in general and their interdependence in the context of chronic trauma in particular have been extensively studied (Boscarino, 2004; Heim et al., 2008; Segerstrom and Miller, 2004a,b). Stress-induced hormonal alterations have been linked with changes in the immune system as well as with behavioral, emotional, and cognitive processes that lead to physical illness and psychiatric problems (De Bellis and Zisk, 2014; Lupien et al., 2009). Such negative effects of stress on physical and mental health is particularly noted during periods of brain maturation and studies have repeatedly shown that trauma carries greater effects on the developing child (Anda et al., 2006; Heim and Nemeroff, 2001). Neural and behavioral plasticity are higher during childhood and adolescence, rendering youth more susceptible to the long-term consequences of prolonged trauma. It is thus important to study the mutual influences of stress and immune responses as they interact in the developing child.

Exposure to war and terror are examples of "mass trauma" where large populations are exposed to the same natural disaster or stressful events at the same time (Masten and Narayan, 2012). Coping with such events requires different mechanisms from those involved in coping with other forms of trauma as the entire family is typically exposed to the same traumatic events and affected mothers may have limited resources to contain the child's fears. Following such trauma, child social abilities and biological systems interact to define trajectories of risk and resilience and shape well-being and health (Heim and Nemeroff, 2001). Since exposure to war and terror is associated with uncertainty (Shaw, 2003), the daily experience of fear, stress, and anxiety increase (Ulmer-Yaniv et al., 2018), markedly increasing the prevalence of anxiety disorders in war-exposed children (Halevi et al., 2016; Heim and Nemeroff, 2001). In addition, many children exposed to war-related stressors suffer from other psychiatric problems, including depression, disruptive behaviors, and somatic symptoms (Allwood et al., 2002; Halevi et al., 2016).

Following mass trauma, maternal sensitivity, empathy, and social attunement serve as improtant protective factors and buffer against the development of psychopathology in children (Feldman and Vengrober, 2011; Masten and Narayan, 2012; Scheering and Zeanah, 2001). Maternal relational behavior is shaped by the mother's psychiatric symptoms and both maternal parenting behavior and maternal psychopathology are influenced by the mother's stress response and hormonal levels. Maternal psychopathology and maladaptive parenting contribute to the sense of instability that is already present in the child's life and may excerbate the traumatic effects. In contrast, the mother's supportive presence and empathic behavior exert a general ‘social buffering’ effect that regulates the child's hormonal, immune, and behavioral systems (Ulmer-Yaniv et al., 2018). Consistent with our "biobehavioral synchrony" model (Feldman, 2012a, 2015, 2016), such biobehavioral maternal influences define the paths by which maternal physiology and behavior modulate the child’s stress respone in a system-specific manner.

Adrenocortical activation is the major hormonal response to stress that organizes physiological and psychological adaptation following exposure to stressors (Sapolsky et al., 2000). Traumatic experiences and chronic stress can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in both adults and children, resulting in altered cortisol (CT) secretion (Chrousos, 2009). In trauma-exposed adults, such dysregulation is often reflected in hypocorticolism, although some studies showed hypercortisolism or no differnce betweeen stress-exposed and control individuals (Klaassens et al., 2012; Miller et al., 2007). In children, most studies reproted that trauma exposure leads to elevated CT levels (Carrion et al., 2002; Cicchetti et al., 2010; De Bellis and Zisk, 2014; Pfeffer et al., 2007), however other studies report lower basal CT levels in trauma-exposed children (Goenjian et al., 1996; King et al., 2001). Consistent with most resaerch, we have previously shown that war-exposed children and mothers had higher CT levels compared to non-exposed controls (Feldman et al., 2013; Halevi et al., 2017).

Stress, trauma, and adrenocortical activation are associated with marked alterations in various components of the immune system (McEwen and Stellar, 1993). Among these, Immunoglobulin A (IgA), which functions as a first-line protector of the body from pathogens, has been extensively investigated. IgA is the most common antibody in the human mucous and levels of its secreted form (s-IgA) in saliva provide a well-validated biomarker of immune-system functioning (Bosch et al., 2002; MacPherson et al., 2008). S-IgA secretion is modulated by physical and psychological stressors (Engeland et al., 2016) as mediated by the degree of anxiety caused by these stressors (Graham et al., 1988; Ulmer-Yaniv et al., 2018; Vermeer et al., 2012). However, results regarding basal levels and responsiveness of s-IgA following acute and chronic stress are contradictory, and evidence shows both excessive and insufficient s-IgA production even after exposure to the same stressors (Bosch et al., 2002; Segerstrom and Miller, 2004a,b).

Notably, most studies on s-IgA have been conducted in adults and very few studies examined the effect of chronic trauma on s-IgA levels in children or adolescents. In one seminal study, adolescents who experienced adverse childhood experiences, including institutionalization or physical abuse, exhibited high levels of salivary s-IgA, particularly against herpes simplex virus (HSV), representing a failure of their cellular immune processes to limit viral (Shirtcliff et al., 2009). Similarly, nine-year old children exposed to chronic war-related stress displayed high levels of s-IgA compared to controls (Ulmer-Yaniv et al., 2018). The stress-induced changes in s-IgA levels may be related to the adrenocortical activation, evidenced by the reported association between CT and s-IgA following prolonged stress, specifically in children (Watamura et al., 2010). However, the results of other studies examining the association between these biomarkers are inconsistent, with studies reporting negative, positive, or no correlation between CT and s-IgA levels (Laurent et al., 2015; Sanchez-Martin et al., 2001; Watamura et al., 2010; Waynforth, 2007).

Although several studies addressed the relations between stress, hormones, immunity, anxiety, and parental behavior, no prior study to our knowledge integrated all components in a single study to test their joint impact on the development of anxiety disorders in stress-exposed youth. Furthermore, previous studies focused on either adults or children, not on both partners of the caregiving dyad, and nearly no research exists on these factors in early adolescence (Hostinar et al., 2014). In the current study, we investigated the multi-dimensional bio-behavioral interplay between the HPA axis, the immune system, and the development of anxiety disorders in youth growing up amidst chronic trauma. We followed a unique cohort of war-exposed adolescence and their mothers living in Sderot, a small Israeli town located less than a mile from the Gaza border and exposed to repeated missile and rockets attack since 2001, with significant exacerbation of the situation in 2005, 2008, and 2014. During the past 12 years, there have been six military operations when the city was under siege and suffered dozens of daily missiles attacks for weeks. Sirens warning of incoming missiles allow citizen 7–15 seconds to reach shelter before explosion. Even during relatively calm periods threats are looming and occasional missiles are launched every few days in addition to the constant fear from tunnel-digging from Gaza. Overall, Sderot and its surrounding area suffered dozens of casualties with hundreds of injured individuals and significant property and infrastructure damage, leading to severe psychological distress among its citizens.

We hypothesized that exposed mothers and children will show elevated levels of CT and s-IgA and that exposed children would display more anxiety symptoms and less social collaboration. We expected that biomarkers in mother and child would be inter-related, consistent with the bio-behavioral synchrony theory (Feldman, 2015). Finally, based on previous findings we build a theoretical model, and assumed that the mother's supportive and sensitive style, as well as her stress biomarkers will shape the child's parallel variables, and that together these factors would explain the association between trauma exposure and anxiety in youth.

Section snippets

Participants

Participants were children and their mothers recruited in two groups; the war-exposed group included families living in the same frontline neighborhoods in Sderot and exposed to repeated war-related trauma and the control group included families living in comparable towns in central Israel who were screened for other trauma. In the initial stage, 232 families of children aged 1.5–5 years (M = 2.76, SD = 0.91) were recruited, of whom 47.6% were males and 47.1% firstborns. The control group

Results

Visual examination of the distributions using density and q-q plots showed that all variables were normally-distributed. However, Jarque-Bera test revealed that child social collaboration and anxiety symptoms scores were not normally distributed (p < 0.05) and these variables were log-transformed.

Differences between groups in study variables appear in Fig. 1 and Table 2. T-tests revealed that exposed mothers and children had significantly higher CT and s-IgA levels compared to controls and

Discussion

Childhood trauma has been defined as “an environmentally induced complex developmental disorder" (De Bellis and Zisk, 2014). Adapting a broad developmental neuroscience perspective that considers how multiple systems and relational patterns evolve over time to shape risk and resilience (Feldman, 2016, 2015) we examined the unique and joint contributions of stress and immune biomarkers and mother-child interactive patterns to adolescents' anxiety disorders in the context of chronic early trauma.

Declaration of interest

Karen Yirmiya, Amir Djalovski, Shai Motsan, Orna Zagoory-Sharon and Ruth Feldman have no conflict of interest to declare.

Acknowledgements

Karen Yirmiya is grateful to the Azrieli Foundation for the award of an Azrieli Fellowship. This work was supported by the Brain and Behavior (NARSAD) award to Ruth Feldman and the Simms-Mann Foundation. We are indebted to the mothers and children who participated in this study.

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