Nestor L. Lopez-Duran

Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis.

Research findings on the hypothalamic-pituitary-adrenal (HPA) axis and pediatric depression reflect a variety of methodological approaches that tap different facets of HPA-axis functions. Partly owing to the methodological heterogeneity of studies, descriptive reviews of this area have produced inconsistent conclusions. Therefore, we conducted formal meta-analyses of pertinent studies in order to advance our understanding of HPA-axis dysregulation in pediatric depression. We examined: (a) 17 published studies of HPA-axis response to the dexamethasone suppression test (DST) in depressed youth (DST; N=926) and (b) 17 studies of basal HPA-axis functioning (N=1332). We also examined descriptively studies that used corticotropin-releasing hormone (CRH) infusion, and those that used psychological probes of the HPA-axis. The global standardized mean effect size difference in HPA-axis response to the DST between depressed and non-depressed youth was 0.57, z=4.18, p<0.01. The global standardized mean difference effect size in basal HPA-axis functioning was 0.20, z=4.53, p<0.01. Age, sex, timing of sampling, dexamethasone dosage, or type of control group was not a significant source of variability for the DST or basal studies. In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors. In conclusion, the HPA-axis system tends to be dysregulated in depressed youth, as evidenced by atypical responses to the DST, higher baseline cortisol values, and an overactive response to psychological stressors. This pattern of dysregulation suggests anomalies within the axiss negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.

Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children.

The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to elicit fear (N = 33) or frustration (N = 32), or a validity check condition (N = 8). This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples for cortisol analysis were collected including 12 post-stress samples at 5-min intervals. Reactive and proactive aggression levels were assessed via the teacher-completed Aggression Behavior Teacher Checklist (Dodge and Coie, J Pers Soc Psychol, 53(6), 1146–1158, 1987). Reactive aggression significantly predicted total and peak post-stress cortisol regardless of stress modality. Proactive aggression was not a predictor of any cortisol index. Examination of pure reactive, proactive, combined, or non-aggressive children indicated that reactive aggressive children had higher cortisol reactivity than proactive and non-aggressive children. Our data suggest that while an overactive HPA-axis response to stress is associated with reactive aggression, stress induced HPA-axis variability does not seem to be related to proactive aggression.

Individual differences in the development of early peer aggression: Integrating contributions of self-regulation, theory of mind, and parenting

This prospective longitudinal study focused on self-regulatory, social-cognitive, and parenting precursors of individual differences in childrens peer-directed aggression at early school age. Participants were 199 3-year-old boys and girls who were reassessed following the transition to kindergarten (5.5-6 years). Peer aggression was assessed in preschool and school settings using naturalistic observations and teacher reports. Childrens self-regulation abilities and theory of mind understanding were assessed during a laboratory visit, and parenting risk (corporal punishment and low warmth/responsiveness) was assessed using interview-based and questionnaire measures. Individual differences in childrens peer aggression were moderately stable across the preschool to school transition. Preschool-age children who manifested high levels of aggressive peer interactions also showed lower levels of self-regulation and theory of mind understanding, and experienced higher levels of adverse parenting than others. Our main finding was that early corporal punishment was associated with increased levels of peer aggression across the transition from preschool to school, as was the interaction between low maternal emotional support and childrens early delays in theory of mind understanding. These data highlight the need for family-directed preventive efforts during the early preschool years.

Differential associations between childhood trauma subtypes and adolescent HPA-axis functioning

UNLABELLED Studies examining the association between childhood trauma exposure and neuroendocrine functioning have returned inconsistent findings. To date, few studies have accounted for the role exposure to different types of childhood trauma may have on different neuroendocrine adaptations, and no study has examined this association using multiple indices of hypothalamic-pituitary-adrenal axis (HPA-axis) functioning. The purpose of this study was to characterize the unique associations between exposure to physical abuse, emotional abuse, and non-intentional trauma, and multiple indices of HPA-axis functioning. METHODS A community sample of 138 youth (aged 9-16) completed the Socially Evaluated Cold Pressor Task (SE-CPT) while their parents completed the Early Trauma Inventory (ETI). All youth then collected 4 diurnal salivary cortisol samples at home across 2 consecutive weekdays. RESULTS High reported exposure to non-intentional trauma was associated with intact diurnal regulation but elevated cortisol at bedtime, physical abuse was associated with faster reactivity to acute stress, and emotional abuse was associated with delayed recovery of cortisol following acute stress. Taken together, there was a heterogeneous relationship among different indices of HPA-axis functioning and trauma subtype. DISCUSSION Different types of childhood trauma exposure are related to distinct anomalies in HPA-axis functioning. This study underscores the importance of research incorporating multiple indices of HPA-axis functioning to inform our understanding of the underlying neuroendocrine dysregulation that may later lead to stress-related psychopathology.

Developmental trajectories of positive and negative affect in children at high and low familial risk for depressive disorder

BACKGROUND Although low positive affect (PA) and high negative affect (NA) have been posited to predispose to depressive disorders, little is known about the developmental trajectories of these affects in children at familial risk for mood disorders. METHODS We examined 202 offspring of mothers who had a history of juvenile-onset unipolar depressive disorder (n = 60) or no history of major psychopathology (n = 80). Offspring participated in up to seven annual, structured laboratory tasks that were designed to elicit PA and NA. RESULTS Growth curve analyses revealed that PA increased linearly and similarly for all children from late infancy through age 9. However, there also were individual differences in early PA. Relative to control peers, offspring of mothers with lifetime unipolar depression had consistently lower levels of PA, and this association remained significant even when controlling for current maternal depression and maternal affect displays. Growth curve analyses also revealed a significant linear decrease in NA in children across time; however, there was no significant inter-individual variation either in early NA or rate of change in NA. CONCLUSION Attenuated PA (rather than excessive NA) may be an early vulnerability factor for eventual unipolar depressive disorder in at-risk children and may represent one pathway through which depression is transmitted.

Frontal EEG asymmetry moderates the effects of stressful life events on internalizing symptoms in children at familial risk for depression

This study examined whether frontal alpha electroencephalographic (EEG) asymmetry moderates the association between stressful life events and depressive symptoms in children at familial risk for depression. Participants included 135 children ages 6 to 13, whose mothers had either a history of depression or no history of major psychiatric conditions. Frontal EEG was recorded while participants watched emotion-eliciting films. Symptoms and stressful life events were obtained via the Child Behavior Check List and a clinical interview, respectively. High-risk children displayed greater relative right lateral frontal activation (F7/F8) than their low-risk peers during the films. For high-risk children, greater relative left lateral frontal activation moderated the association between stressful life events and internalizing symptoms. Specifically, greater relative left lateral frontal activation mitigated the effects of stress in at-risk children.

Facebook use and depressive symptomatology

The popularity of social networking sites, such as Facebook, has increased rapidly over the past decade, especially among youth. Consequently, the impact of Facebook use on mental health problems (e.g., depressive symptomatology) has become a recent area of concern. Yet, evidence for such a link has been mixed and factors that contribute to heterogeneity of findings have not been identified. In this study, we examined whether the association between Facebook use and depressive symptoms is moderated by individual factors (i.e., personality and sex). To this end, we measured Facebook use, depressive symptoms, and personality domains (i.e., extroversion and neuroticism) among 237 young adults. No direct association was found between Facebook use and depressive symptoms. However, for females with high neuroticism, more frequent Facebook use was associated with lower depressive symptoms. Our findings suggest a complex relationship between Facebook use and depressive symptomatology that appears to vary by sex and personality. Facebook use may be protective against depressive symptoms for female users with high levels of neuroticism, while Facebook use may be unrelated to depressive symptoms among males.

Individual differences in cortisol responses to fear and frustration during middle childhood.

The purpose of this study was to examine individual differences in the activation and regulation of the hypothalamic-pituitary-adrenal (HPA) axis in prepubertal children after exposure to two different stress modalities and to evaluate the utility of an individual differences approach to the examination of HPA axis functioning. After a 30-min controlled baseline period, 73 7-year-olds (40 boys and 33 girls) were randomly assigned to a validity check condition or one of two experimental tasks designed to elicit fear or frustration. This was followed by a 60-min controlled regulation phase. A total of 17 saliva samples were collected, including 12 poststress samples at 5-min intervals. There was a significant stress modality effect, with children exposed to the fear condition reaching peak cortisol levels at 25min poststress and those exposed to the frustration condition reaching peak levels at 45min poststress. There was no difference in peak cortisol levels between the stress modalities. Individual variability across conditions was significant, with participants reaching peak levels as early as 10min poststress and as late as 60min poststress. Our data suggest that analysis of individual curves prior to making group-level comparisons may improve the explanatory power of HPA axis behavior models.

Facial emotion expression recognition by children at familial risk for depression: high-risk boys are oversensitive to sadness.

BACKGROUND Offspring of depressed parents are at greatly increased risk for mood disorders. Among potential mechanisms of risk, recent studies have focused on information processing anomalies, such as attention and memory biases, in the offspring of depressed parents. In this study we examined another information processing domain, perceptual sensitivity to emotion cues in facial expressions, as a potential mechanism of risk that characterizes the offspring of depressed parents. METHODS The study included 64 children at familial-risk for depression and 40 low-risk peers between the ages 7 and 13(Mage = 9.51; SD = 2.27). Participants were presented with pictures of facial expressions that varied in emotional intensity from neutral to full-intensity sadness or anger (i.e., emotion recognition), or pictures of faces morphing from anger to sadness (emotion discrimination). After each picture was presented, children indicated whether the face showed a specific emotion (i.e., sadness, anger) or no emotion at all (neutral) using a forced choice paradigm. We examined group differences in the intensity of emotion that suggested greater sensitivity to specific emotions. RESULTS In the emotion recognition task, boys (but not girls) at familial-risk for depression identified sadness at significantly lower levels of emotional intensity than did their low-risk peers. The high and low-risk groups did not differ with regard to identification of anger. In the emotion discrimination task, both groups displayed over-identification of sadness in ambiguous mixed faces but high-risk youth were less likely to show this labeling bias than their peers. CONCLUSION Our findings are consistent with the hypothesis that enhanced perceptual sensitivity to subtle traces of sadness in facial expressions may be a potential mechanism of risk among boys at familial-risk for depression. This enhanced perceptual sensitivity does not appear to be due to biases in the labeling of ambiguous faces.

Modeling neuroendocrine stress reactivity in salivary cortisol: adjusting for peak latency variability.

Abstract In this report, we present growth curve modeling (GCM) with landmark registration as an alternative statistical approach for the analysis of time series cortisol data. This approach addresses an often-ignored but critical source of variability in salivary cortisol analyses: individual and group differences in the time latency of post-stress peak concentrations. It allows for the simultaneous examination of cortisol changes before and after the peak while controlling for timing differences, and thus provides additional information that can help elucidate group differences in the underlying biological processes (e.g. intensity of response, regulatory capacity). We tested whether GCM with landmark registration is more sensitive than traditional statistical approaches (e.g. repeated measures ANOVA – rANOVA) in identifying sex differences in salivary cortisol responses to a psychosocial stressor (Trier Social Stress Test –TSST) in healthy adults (mean age 23). We used plasma ACTH measures as our “standard” and show that the new approach confirms in salivary cortisol the ACTH finding that males had longer peak latencies, higher post-stress peaks but a more intense post-peak decline. This finding would have been missed if only saliva cortisol was available and only more traditional analytic methods were used. This new approach may provide neuroendocrine researchers with a highly sensitive complementary tool to examine the dynamics of the cortisol response in a way that reduces risk of false negative findings when blood samples are not feasible.