Lisa S. Badanes

Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Dysphoric Children and Adolescents: Cortisol Reactivity to Psychosocial Stress from Preschool Through Middle Adolescence

BACKGROUND Most depressed adults exhibit dysregulation of the hypothalamic-pituitary-adrenal axis, including cortisol hyperreactivity to psychosocial challenge. In contrast, remarkably little is known about hypothalamic-pituitary-adrenal axis activity in response to psychosocial challenge among at-risk children and adolescents. This study examined cortisol response to psychosocial challenge in nondepressed, at-risk, dysphoric and nondysphoric control youth across different developmentally salient age groups (preschool, third-, sixth-, and ninth-graders). METHODS Two samples of youth (Study 1-preschoolers; Study 2-third-, sixth-, and ninth-graders) without a history of clinical depression were administered developmentally appropriate psychosocial challenges. Of these nondepressed children, we examined youth at high-risk (n = 60) and low-risk (n = 223) status, as defined by elevated but subthreshold dysphoric symptoms according to multiple informants. Cortisol levels were assessed before and after a psychosocial stressor. RESULTS Nondysphoric control youth at all ages displayed the expected cortisol rise to challenge followed by return to baseline. However, prepubertal, at-risk, dysphoric children--specifically preschoolers and third-graders--exhibited cortisol hyporeactivity to challenge, whereas postpubertal dysphoric adolescents (ninth-graders) displayed hyperreactivity to the stressor. Additional analyses revealed that this switch from cortisol hyporeactivity to hyperreactivity among at-risk, dysphoric youth occurred as a function of pubertal development. CONCLUSIONS Findings suggest a developmental switch in cortisol response for at-risk, dysphoric youth from preschool through adolescence and have implications for a developmental pathophysiological understanding of how at-risk youth across the lifespan might develop depressive disorder.

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 childrens 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.

Association between 5-HTTLPR and Borderline Personality Disorder Traits among Youth.

This study provides the first genetic association examination of borderline personality disorder (BPD) traits in children and adolescents (ages 9–15) using two independent samples of youth recruited from the general community. We tested the a priori hypothesis that the serotonin transporter promoter gene (5-HTTLPR) would relate specifically to BPD traits in youth. This association was hypothesized based on prior genetic association research with BPD adults and theory positing that emotion dysregulation may be a core risk process contributing to BPD. Youth provided DNA via buccal cells. Both youth and a parent completed self-report measures assessing youths BPD traits and depressive symptoms. Results from both Study 1 (N = 242) and an independent replication sample of Study 2 (N = 144) showed that carriers of the short allele of 5-HTTLPR exhibited the highest levels of BPD traits. This relation was observed even after controlling for the substantial co-occurrence between BPD traits and depressive symptoms. This specific association between 5-HTTLPR and BPD traits among youth supports previous genetic associations with adults diagnosed with BPD and provides preliminary support for a developmental extension of etiological risk for BPD among youth.

Cortisol reactivity to stress among youth: stability over time and genetic variants for stress sensitivity.

Stress sensitivity may be one process that can explain why some genetically at-risk individuals are more susceptible to some types of stress-reactive psychopathologies. Dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, including cortisol reactivity to challenge, represents a key aspect of stress sensitivity. However, the degree of stability over time among youth, especially differential stability as a function of particular genetic variants, has not been investigated. A general community sample of children and adolescents (mean age = 11.4; 56% girls) provided a DNA sample and completed 2 separate laboratory stress challenges, across an 18-month follow-up (N = 224 at Time 1; N = 194 at Time 2), with repeated measures of salivary cortisol. Results showed that test-retest stability for several indices of cortisol reactivity across the laboratory challenge visits were significant and of moderate magnitude for the whole sample. Moreover, gene variants of several biologically plausible systems relevant for stress sensitivity (especially 5-HTTLPR and CRHR1) demonstrated differential stability of cortisol reactivity over 18-months, such that carriers of genotypes conferring enhanced environmental susceptibility exhibited greater stability of cortisol levels over time for some LHPA axis indices. Findings suggest that LHPA axis dysregulation may exhibit some trait-like aspects underlying stress sensitivity in youth, especially for those who carry genes related to greater genetic susceptibility to environmental stress.

Developmental perspectives on vulnerability to nonsuicidal self-injury in youth

Nonsuicidal self-injury (NSSI) is defined as intentionally causing bodily harm to oneself without the intent to kill oneself. Recently, there has been an increase in research aimed at understanding why individuals, especially youth and young adults, engage in NSSI. This chapter explores the emergence and maintenance of NSSI from a developmental perspective. Epidemiological research suggests that rates of NSSI increase dramatically from early adolescence to young adulthood. No study has investigated NSSI in youth younger than age 10. Current understanding of how emotion and cognitions as well as interpersonal processes play a role in the emergence and maintenance of NSSI is explored. Further, the role of biology (e.g., neurological underpinnings, genetic associations, HPA-axis functioning) on NSSI is explored. Throughout the chapter, particular limitations (e.g., sample selection, measurement issues) in the extant corpus of knowledge are highlighted. Finally, we consider future research directions that may inform developmentally sensitive understanding of the proximal and distal risk factors that may affect the emergence and maintenance of NSSI across the life span.

Youth offspring of mothers with posttraumatic stress disorder have altered stress reactivity in response to a laboratory stressor

Parental Posttraumatic Stress Disorder (PTSD), particularly maternal PTSD, confers risk for stress-related psychopathology among offspring. Altered hypothalamic-pituitary-adrenal (HPA) axis functioning is one mechanism proposed to explain transmission of this intergenerational risk. Investigation of this mechanism has been largely limited to general stress response (e.g., diurnal cortisol), rather than reactivity in response to an acute stressor. We examined cortisol reactivity in response to a laboratory stressor among offspring of mothers with a lifetime diagnosis of PTSD (n=36) and age- and gender- matched control offspring of mothers without PTSD (n=36). Youth (67% girls; mean age=11.4, SD=2.6) participated in a developmentally sensitive laboratory stressor and had salivary cortisol assessed five times (one pre-stress, one immediate post-stress, and three recovery measures, spaced 15min apart). Results were consistent with the hypothesis that offspring of mothers with PTSD would exhibit a dysregulated, blunted cortisol reactivity profile, and control offspring would display the expected adaptive peak in cortisol response to challenge profile. Findings were maintained after controlling for youth traumatic event history, physical anxiety symptoms, and depression, as well as maternal depression. This finding contributes to the existing literature indicating that attenuated HPA axis functioning, inclusive of hyposecretion of cortisol in response to acute stress, is robust among youth of mothers with PTSD. Future research is warranted in elucidating cortisol reactivity as a link between maternal PTSD and stress-related psychopathology vulnerability among offspring.

Parental depression and child cognitive vulnerability predict children's cortisol reactivity

Risk for depression is expressed across multiple levels of analysis. For example, parental depression and cognitive vulnerability are known markers of depression risk, but no study has examined their interactive effects on childrens cortisol reactivity, a likely mediator of early depression risk. We examined relations across these different levels of vulnerability using cross-sectional and longitudinal methods in two community samples of children. Children were assessed for cognitive vulnerability using self-reports (Study 1; n = 244) and tasks tapping memory and attentional bias (Study 2; n = 205), and their parents were assessed for depression history using structured clinical interviews. In both samples, children participated in standardized stress tasks and cortisol reactivity was assessed. Cross-sectionally and longitudinally, parental depression history and child cognitive vulnerability interacted to predict childrens cortisol reactivity; associations between parent depression and elevated child cortisol activity were found when children also showed elevated depressotypic attributions as well as attentional and memory biases. Findings indicate that models of childrens emerging depression risk may benefit from the examination of the interactive effects of multiple sources of vulnerability across levels of analysis.

Self-Regulation and Economic Stress in Children of Hispanic Immigrants and Their Peers: Better Regulation at a Cost?

ABSTRACT Research Findings: Although there is a well-established relationship between economic stress and children’s self-regulation, few studies have examined this relationship in children of Hispanic immigrants (COHIs), a rapidly growing population. In a sample of preschool children (N = 165), we examined whether economic stress predicted teacher evaluations of children’s self-regulation, whether economic stress predicted children’s physiological reactivity (via cortisol levels), and whether economic stress had a similar effect on self-regulation and children’s cortisol for COHI versus nonimmigrant children. Greater economic stress was associated with poorer child self-regulation and heightened physiological reactivity across a challenging classroom task for the sample as a whole. However, when we examined children by group, greater economic stress was associated with poorer teacher-reported self-regulation for nonimmigrant children only. In contrast, greater economic stress was related to greater cortisol reactivity across a challenge task for COHIs but not for nonimmigrants. Practice or Policy: Results demonstrate the importance of considering physiological indices of self-regulation (heightened stress physiology), in addition to traditional external indices (teacher report), when assessing self-regulation or risk more generally among preschool samples that are diverse in terms of ethnicity, economic risk, and parents’ nativity.