Relations between mucosal immunity and children's mental health: The role of child sex

This study examines relations between children's salivary interleukin-6 (IL-6) and secretory immunoglobulin A (SIgA) and mental health. Child sex was considered as a moderator of relations. Data were from 329 normally developing children (M age = 9.85 years; SD = .98 years); 67% of children were European American and 33% were African American. Saliva samples were obtained during the afternoon and assayed for SIgA and IL-6. Parents completed questionnaire measures of child internalizing and externalizing symptoms, and children completed self-report measures of anxiety and depression. Structural equation models were fit to the data, and indicated that greater levels of salivary IL-6 and SIgA were associated with adjustment problems more strongly for girls than for boys.     

The “Heart” of depression during early adolescence

This study examined the concurrent associations linking youths’ parasympathetic nervous system activity, specifically baseline respiratory sinus arrhythmia (RSA) and respiratory sinus arrhythmia reactivity (RSAR; vagal withdrawal), with youth depression risk in a community sample of young adolescents. Youth gender was examined as a moderator of associations. Participants included 100 youth (53% boys; M age = 11.05 years, SD = 0.33; 43% ethnic minorities), along with their mothers and teachers. Youth and mothers participated in a laboratory protocol involving a peer problem-solving conversation, during which youths’ physiological activity was measured. Youth reported on their depressive symptoms. Teachers reported on youth depression risk via internalizing symptoms and emotion regulation (e.g., emotion lability/negativity). Results from regression analyses revealed that youths’ vagal withdrawal during the mother-youth peer problem conversation was associated with lower youth-reported depressive symptoms. Further, gender moderated the associations linking youth baseline RSA and RSAR with youth depression risk. Specifically, among girls but not boys, higher baseline RSA was associated with lower depressive symptoms and emotion lability/negativity, and higher RSAR (i.e., vagal withdrawal) was linked with lower internalizing symptoms. Findings contribute to the relatively small literature linking youth parasympathetic functioning with depression risk, and point to specific implications for girls.     

Parasympathetic nervous system activity and children's sleep

We examined indices of children's parasympathetic nervous system activity (PNS), including respiratory sinus arrhythmia during baseline (RSAB) and RSA reactivity (RSAR), to a laboratory challenge, and importantly the interaction between RSAB and RSAR as predictors of multiple parameters of children's sleep. Lower RSAR denotes increased vagal withdrawal (reductions in RSA between baseline and task) and higher RSAR represents decreased vagal withdrawal or augmentation (increases in RSA between baseline and task). A community sample of school‐attending children (121 boys and 103 girls) participated [mean age = 10.41 years; standard deviation (SD) = 0.67]. Children's sleep parameters were examined through actigraphy for 7 consecutive nights. Findings demonstrate that RSAB and RSAR interact to predict multiple sleep quality parameters (activity, minutes awake after sleep onset and long wake episodes). The overall pattern of effects illustrates that children who exhibit more disrupted sleep (increased activity, more minutes awake after sleep onset and more frequent long wake episodes) are those with lower RSAB in conjunction with lower RSAR. This combination of low RSAB and low RSAR probably reflects increased autonomic nervous system arousal, which interferes with sleep. Results illustrate the importance of individual differences in physiological regulation indexed by interactions between PNS baseline activity and PNS reactivity for a better understanding of children's sleep quality.     

Stress hormone levels of children of depressed mothers

Research suggests that disruptions in early caretaking can have long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis, which mediates the stress response. Children of depressed mothers are at increased risk for developing internalizing problems in part because of disruptions in their caretaking environment. The present study investigated whether children of depressed mothers exhibit elevated salivary cortisol levels. Salivary cortisol samples were collected from 45 7- to 8-year-old children of mothers with a history of depression and 29 children of nondepressed mothers. Samples were collected soon after arrival to the laboratory and after a mild laboratory stressor and at home after wakeup and before bedtime. Children who had elevated levels of intemalizing symptoms and whose mothers had a history of depression showed elevated laboratory baseline cortisol levels. Children who were reported to have clinically significant internalizing symptoms were also more likely to show an elevated stress response to a mild laboratory stressor. When the longitudinal history of maternal depression was examined, matemal depression during the child's first 2 years of life was the best predictor of elevations in baseline cortisol at age 7 years. This study provides evidence that internalizing symptoms exist in conjunction with a more reactive hormonal stress system in children of depressed mothers. The results also provide preliminary evidence that exposure to maternal depression in the first 2 years of life may be related to children's cortisol levels later in life.     

Blunted HPA axis response to stress is related to a persistent Dysregulation Profile in youth

The Child Behavior Checklist Dysregulation Profile (DP) in youth has been shown to be a predictor of psychopathology later in life. We examined the activity of the hypothalamic pituitary adrenal (HPA) axis in youth with remitted, new, persistent, and no DP. Data from 489 youth (47% boys) participating in a Dutch longitudinal general population study were included (Wave 1 mean age = 11.5, Wave 2 = 14.2). Wave 2 diurnal cortisol patterns and levels in response to a laboratory stress paradigm were compared in youth with DP at Wave 1 only, Wave 2 only, both Waves, and neither Wave. Youth with the DP at Wave 2 only or at both time points showed blunted cortisol responses to stress relative to the other two groups. There were no group or sex differences in diurnal cortisol activity. More research is needed to determine how the association between DP symptoms and HPA axis functioning changes over time.     

Cardiac vagal control and children's adaptive functioning: A meta-analysis

Polyvagal theory has influenced research on the role of cardiac vagal control, indexed by respiratory sinus arrhythmia withdrawal (RSA-W) during challenging states, in children's self-regulation. However, it remains unclear how well RSA-W predicts adaptive functioning (AF) outcomes and whether certain caveats of measuring RSA (e.g., respiration) significantly impact these associations. A meta-analysis of 44 studies (n = 4996 children) revealed small effect sizes such that greater levels of RSA-W were related to fewer externalizing, internalizing, and cognitive/academic problems. In contrast, RSA-W was differentially related to children's social problems according to sample type (community vs. clinical/at-risk). The relations between RSA-W and children's AF outcomes were stronger among studies that co-varied baseline RSA and in Caucasian children (no effect was found for respiration). Children from clinical/at-risk samples displayed lower levels of baseline RSA and RSA-W compared to children from community samples. Theoretical/practical implications for the study of cardiac vagal control are discussed.     

The role of childhood abuse in HPA-axis reactivity in Social Anxiety Disorder: A pilot study

Background

Studies on depression have found that childhood abuse (CA) is associated with a persistent sensitization of the hypothalamic-pituitary-adrenal (HPA)-axis to stress in adulthood. So far, it is unknown whether this HPA-axis sensitization is specific to depression, or whether this is a more general outcome associated with CA in patients with mood and anxiety disorders. The aim of this study was to investigate whether CA is associated with enhanced cortisol reactivity to psychosocial stress in Social Anxiety Disorder (SAD).

Methods

Salivary cortisol levels before, during, and after exposure to psychosocial stress (i.e., Trier Social Stress Task, TSST) in SAD patients with a history of childhood abuse (SAD + CA, n = 9) were compared to cortisol levels in SAD patients without a history of childhood abuse (SAD − CA, n = 9), patients with PTSD related to childhood abuse (n = 16), and healthy controls without a history of childhood abuse (n = 16).

Results

Analyses showed that the SAD + CA group had a strongly increased cortisol reactivity (mean peak: 17.5 ± 1.9 nmol/l) compared to SAD − CA (mean peak: 9.0 ± 1.1 nmol/l), PTSD (mean peak: 9.0 ± 1.1 nmol/l) and healthy controls (mean peak: 9.6 ± 1.4 nmol/l), whereas baseline cortisol levels did not differ. The enhanced increase in the SAD + CA group was not explained by stronger anxiety in response to the TSST.

Conclusions

Consistent with the findings in depression, these results show for the first time that childhood abuse is also associated with strongly increased cortisol reactivity in SAD. When replicated in a larger sample, these findings may have important implications for the treatment of SAD.     

Hypocortisolism as a potential marker of allostatic load in children: associations with family risk and internalizing disorders

Although the majority of research attention to the hypothalamic-pituitary-adrenal (HPA) axis in stress-related disorders and as a marker of allostatic load has focused on overactivation of this stress system, theory and data clearly indicate that underactivation is also an important type of dysregulation. In the current study we focused on low cortisol, exploring a constellation of risk factors including stress exposure, maternal depression, and attenuated basal and stress reactive cortisol in two samples of children. The first sample was comprised of 110 preschoolers living in high-stress environments. Cortisol was assessed across the day at home and at child care as well as across two stress paradigms. These data were used to classify whether children's HPA axis activity was attenuated. Serious family financial strain, maternal depression, and attenuated cortisol all made unique contributions in models predicting current clinical levels of internalizing symptoms as rated by mothers and teachers. The second sample was 166 third, sixth, and ninth graders studied five times across a 1-year period. Maternal and child depression were determined through structured clinical interviews, and stress exposure was assessed via checklist and interview techniques with the child and parent. Cortisol was assessed multiple times across a lab visit at Time 1, and these data were combined into a single continuous measure. Cortisol concentrations across the lab visit interacted with stress exposure across the year such that children with lower average cortisol at Time 1 and increased stress across the 12 months showed elevated levels of internalizing symptoms. Based on these and related data we propose that prior to puberty low cortisol may be an important marker of allostatic load, particularly for risk of depression and anxiety.     

Family environment is associated with HPA-axis activity in adolescents. The TRAILS study

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age = 11.08, SD = 0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.     

Affective and neuroendocrine stress reactivity to an academic examination: influence of the 5-HTTLPR genotype and trait neuroticism

The current study examined the singular and interactive effects of the 5-HTTLPR genotype and trait neuroticism on affective and physiological stress responses to an academic examination in healthy undergraduate students. From 771 students, 46 short/short (S/S)-allele carriers and 48 long/long (L/L)-allele carriers with the lowest and the highest neuroticism scores (80 females, 14 males; mean age ± SD: 20.3 ± 1.7 years) were selected. Salivary cortisol concentrations, mood and perceived stress were assessed before and after a 2-h written examination and compared with a control day. Negative mood, perceived stress and cortisol significantly increased during the examination compared to the control day. Negative stress effects on mood and perceived stress were significantly larger for S/S-allele carriers compared to L/L-allele carriers, regardless of trait neuroticism. Since vulnerability to real-life stressors is an important risk factor for depression pathogenesis, this may be a mediating factor making S/S-allele carriers more susceptible for depression symptoms.     

Salivary cortisol levels in children of low-income women with high depressive symptomatology

Children (N = 324 boys, 315 girls) between the ages of 2.5 and 6 (mean age = 3.63) were identified in a house to house survey in low-income areas (income <20th percentile nationally) of urban Mexico. The Center for Epidemiologic Studies-Depression Scale was administered to mothers of all children. Salivary cortisol samples were taken in children as a measure of hypothalamic-pituitary-adrenocortical (HPA) system activity at time of arrival (baseline, Time 0), 25 min after arrival (Time 1), and 50 min after arrival (Time 2). Between Time 0 and Time 1, children were administered several cognitive tests. Results of hierarchical linear modeling analyses revealed that higher levels of maternal depressive symptoms were associated with lower baseline cortisol levels in their children (p < .05), while controlling for age, gender, and time since awakening. Higher levels of maternal depressive symptoms were associated with less of an increase in salivary cortisol to the arrival of the experimenters and subsequent cognitive testing (p < .05). All results were moderated by gender, with enhanced cortisol response in girls and no response in boys. These results suggest that among very low-income families, high maternal depressive symptoms are associated with hypoactivity of the HPA system in children, particularly boys.     

Co-activation of SAM and HPA responses to acute stress: A review of the literature and test of differential associations with preadolescents’ internalizing and externalizing

Understanding co-activation patterns of the hypothalamic-pituitary-adrenal axis (HPA) and sympathetic adrenal medullary (SAM) during early adolescence may illuminate risk for development of internalizing and externalizing problems. The present study advances empirical work on the topic by examining SAM-HPA co-activation during both the reactivity and recovery phases of the stress response following acute stress exposure. Fourth and fifth grade boys and girls (N = 149) provided cortisol and alpha-amylase via saliva at seven times throughout a 95-min assessment in which they were administered the modified Trier Social Stress Test. Parents reported on adolescents’ life stress, pubertal development, medication use, and externalizing problems. Adolescents reported their own internalizing symptoms. Multiple linear regressions tested both direct and interactive effects of SAM and HPA reactivity and recovery on internalizing and externalizing problems. Results from these analyses showed that whereas SAM and HPA reactivity interacted to predict internalizing symptoms, it was their interaction during the recovery phase that predicted externalizing. Concurrent high SAM and HPA reactivity scores predicted high levels of internalizing and concurrently low SAM and HPA recovery scores predicted high levels of externalizing. Implications of the findings for further study and clinical application are discussed.     

Psychophysiological correlates of parenting behavior in mothers of young children

This study investigated HPA and vagal functioning as correlates of parenting in mothers of 175 six‐month‐old children. Salivary cortisol indexed HPA functioning and respiratory sinus arrhythmia (RSA) reduction indexed vagal regulation. Positive engagement and negative intrusiveness were observed during the Face‐to‐Face Still Face Paradigm (FFSFP) reunion and a semi‐structured free play episode. Mixed modeling was used to examine differences in maternal behaviors across contexts as a function of psychophysiology. Main effects of cortisol levels, as well as interactions with RSA reduction and context, predicted negative intrusiveness. Mothers with high cortisol exhibited more negative intrusiveness if they also had lower RSA reduction. Mothers were also less negatively intrusive during the FFSFP than the free play if they had lower cortisol levels. There were no associations between psychophysiological measures and positive engagement. The findings suggest: (1) that parenting behaviors are associated with maternal stress physiology; (2) considerations of single physiological systems related to parenting behaviors may be incomplete; and (3) type and context of behaviors must be considered when examining biobehavioral associations with parenting. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 650–661, 2009     

Self- or parent report of (co-occurring) internalizing and externalizing problems,and basal or reactivity measures of HPA-axis functioning: A systematic evaluation of the internalizing-hyperresponsivity versus externalizing-hyporesponsivity HPA-axis hypothesis

Background

Previous research findings on the link between adolescents’ psychopathology and hypothalamic–pituitary–adrenal (HPA) axis activity have been heterogeneous.

Method

Adolescents (n = 211) with a preadolescent DSM-IV diagnosis participated in a lab-based social stress task. Saliva cortisol was assessed at awakening and during social stress. It was investigated if continuous measures of internalizing and externalizing problems and their interaction, using both self- and parent report, were associated with basal or reactivity measures of HPA-axis functioning

Results

During social stress, an enhanced total release of cortisol was associated with self-reported internalizing problems and a blunted total release of cortisol with self-reported externalizing problems. Post hoc analyses revealed that the association between enhanced cortisol output and internalizing problems held for boys but not for girls. Associations with morning cortisol measures were overall weak

Conclusions

Only in the context of stress, and particularly when based on self-report, blunted cortisol output was associated with externalizing and enhanced cortisol output with internalizing problems. Our broad approach demonstrates the importance of who reports on psychopathology, the use of dimensional measures of psychopathology, simultaneous analysis of internalizing and externalizing problems, and the use of awakening and social stress related measures of cortisol.     

Applying the polyvagal theory to children's emotion regulation: Social context, socialization, and adjustment

Effective emotion regulation is essential for children's positive development. Polyvagal theory provides a framework for understanding how parasympathetic regulation of cardiac activity contributes to children's adaptive versus maladaptive functioning. Maintenance of cardiac respiratory sinus arrhythmia (RSA) under social challenge should support emotion regulation and behavioral adjustment. Children's effective parasympathetic regulation and behavioral adjustment should be supported by appropriate parental socialization. These proposals were evaluated in a short-term longitudinal study of 94 preschool-aged children. Parenting and basal RSA were measured at home, then 6-10 months later behavioral adjustment and RSA in lab baseline and socially challenging contexts were measured. Children with relatively higher RSA in social challenge than at baseline (DeltaRSA) had fewer internalizing problems (IP) and externalizing problems (EP), and better behavioral self-regulation (SR). Mothers who used more negative control had children with lower DeltaRSA, more IP and EP, and less SR. Structural equation modeling showed that vagal regulation mediated associations between maternal negative control and children's adjustment; maternal negative control did not predict EP or SR after accounting for DeltaRSA. Associations were consistent across boys and girls, with one exception: Higher DeltaRSA was significantly associated with fewer EP in boys only. These findings suggest that the practical significance of physiological regulation might be best revealed in ecologically valid procedures, and that children's physiological mechanisms of emotion regulation are shaped by their experiences of parental socialization.     

Children’s sleep,skin conductance level and mental health

We examined relations between children’s sympathetic nervous system activity, indexed by skin conductance level (SCL) during baseline and reactivity to a challenging task and their sleep problems. We also assessed SCL as a moderator of associations between children’s sleep problems and their mental health. A sample of healthy and typically developing school‐attending children (78 boys and 98 girls) participated (mean age = 8.7 years; standard deviation = 0.36). Sleep was assessed via actigraphy and self‐reports. Parents reported on children’s externalizing behaviors and children reported their internalizing symptoms. Findings demonstrate that sleep disruptions (duration, quality) are associated with lower basal SCL. In the context of sleep problems, a lower level of basal SCL functioned as a vulnerability factor for depression symptoms and worse self‐esteem. Further, children with both increased SCL reactivity and sleep problems were at risk for depression symptoms. Results illustrate the significance of simultaneous examinations of various biological and physiological systems in the prediction of children’s wellbeing.     

Adrenocortical responses to strangers in preschoolers: relations with parenting, temperament, and psychopathology

Previous research has provided inconsistent evidence for the relations between young children's hypothalamic-pituitary-adrenal (HPA) functioning and their temperament, parenting, and adjustment. Building biopsychosocial models of adjustment, we examined how temperamental inhibition and maternal punishment contributed to preschoolers' adrenocortical activity while interacting with adult strangers. We also examined whether HPA functioning moderated relations between dispositional and familial factors and children's internalizing and externalizing problems. A total of 402 preschool-aged children from three independent samples with parallel and overlapping measures were studied. Salivary cortisol levels were measured twice while interacting with adult strangers during testing protocols. Mothers reported on temperamental inhibition, maternal punishment and children's problems. Maternal punishment predicted higher cortisol levels 20 and 65 min after meeting adult strangers. Prolonged cortisol elevation was associated with having fewer externalizing problems. Boys who experienced more maternal punishment and had higher cortisol 20 min after meeting strangers manifested more externalizing problems. Girls who were more inhibited and had prolonged cortisol elevations had more internalizing problems. In accord with biopsychosocial models of psychopathology, HPA functioning in preschoolers was sensitive to variations in socialization experiences, and moderated children's risk for emotional and behavioral problems.     

Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene

The serotonin 5HTR2C receptor has been shown to mediate HPA axis activation during stress. We hypothesized that a functional polymorphism (rs6318) of the 5HTR2C gene would be associated with HPA axis response to a laboratory stress protocol. The present sample consisted of 41 men (22 African Americans, 19 Caucasians). We found that at rest men with the more active rs6318 Ser23 C allele had similar cortisol values compared to those with the less active Cys23 G allele. During laboratory stress, however, men with the Ser23 C allele exhibited the predicted significantly higher cortisol levels (p < 0.001), as well as larger increases in anger (p = 0.08) and depressive mood (p = 0.006) ratings, compared to the Cys23 G carriers. The increase in cortisol was significantly related to the increases in ratings of anger and depression assessed before and after the emotion induction, and these correlations became nonsignificant when rs6318 genotype was covaried. We conclude that genetic variation in 5HTR2C may be associated with HPA axis activation and stimulated by emotional stress, and also with both psychological and physiological endophenotypes that increase the risk of cardiovascular disease and type-2 diabetes.     

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5 mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease.     

Low Vagal Tone Magnifies the Association Between Psychosocial Stress Exposure and Internalizing Psychopathology in Adolescents

Vagal tone is a measure of cardiovascular function that facilitates adaptive responses to environmental challenge. Low vagal tone is associated with poor emotional and attentional regulation in children and has been conceptualized as a marker of sensitivity to stress. We investigated whether the associations of a wide range of psychosocial stressors with internalizing and externalizing psychopathology were magnified in adolescents with low vagal tone. Resting heart period data were collected from a diverse community sample of adolescents (ages 13–17; N = 168). Adolescents completed measures assessing internalizing and externalizing psychopathology and exposure to stressors occurring in family, peer, and community contexts. Respiratory sinus arrhythmia (RSA) was calculated from the interbeat interval time series. We estimated interactions between RSA and stress exposure in predicting internalizing and externalizing symptoms and evaluated whether interactions differed by gender. Exposure to psychosocial stressors was associated strongly with psychopathology. RSA was unrelated to internalizing or externalizing problems. Significant interactions were observed between RSA and child abuse, community violence, peer victimization, and traumatic events in predicting internalizing but not externalizing symptoms. Stressors were positively associated with internalizing symptoms in adolescents with low RSA but not in those with high RSA. Similar patterns were observed for anxiety and depression. These interactions were more consistently observed for male than female individuals. Low vagal tone is associated with internalizing psychopathology in adolescents exposed to high levels of stressors. Measurement of vagal tone in clinical settings might provide useful information about sensitivity to stress in child and adolescent clients.