Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. METHODS: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. RESULTS: MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor's degree or higher (OR 0.42, 95% CI 0.22-0.80, p = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; p = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. DISCUSSION: Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.

Biological sensitivity to adolescent-parent discrepancies in perceived parental warmth.

Introduction: Parenting behaviors are formative to the psychological development of young people; however, parent and adolescent perceptions of parenting are only moderately correlated with each other. Whereas discrepant perceptions may represent a normative process of deindividuation from caregivers in some adolescents, in others a discrepancy might predict psychological maladjustment. The biological sensitivity to context model provides a framework from which individual differences in development can be estimated in adolescents whose perceptions of parenting diverge from those of their parents. Methods: At baseline we obtained diurnal cortisol samples from US adolescents (M = 13.37 years of age, SD = 1.06) as well as parents' and adolescents' ratings of parental warmth; we obtained adolescent-reported symptoms of psychopathology at baseline and again at follow-up two years later (N = 108, 57.5% female). We estimated waking cortisol, cortisol awakening response, and daytime cortisol slopes using piecewise regression models. Results: Lower adolescent than parent ratings of parental warmth predicted increased externalizing symptoms at follow-up. Higher waking cortisol and steeper cortisol awakening response and daytime slopes predicted increased internalizing symptoms at follow-up. Further, discrepant ratings of parental warmth interacted with cortisol awakening response and daytime slopes such that greater discrepancies predicted greater increases in externalizing symptoms in adolescents with steeper cortisol slopes. Conclusions: These findings indicate that steeper changes in cortisol production throughout the day index a greater sensitivity to perceived parental warmth. Lower adolescent than parent ratings of parental warmth may represent dysfunction in the parental relationship rather than a normative process of deindividuation in adolescents with steeper diurnal cortisol slopes.

ADHD symptoms and diurnal cortisol in adolescents: The importance of comorbidities.

BACKGROUND: Altered regulation of diurnal cortisol has been associated with both dimensional symptoms and clinical diagnoses of attention deficit-hyperactivity disorder (ADHD). Indeed, a recent meta-analysis suggests that lower diurnal cortisol output may be a biomarker of attention deficit-hyperactivity disorder (ADHD); importantly, however, the influence of psychiatric comorbidities on this association has not been characterized. Approximately two-thirds of children with ADHD have at least one co-occurring neuropsychiatric condition, and altered HPA-axis function has been implicated in many of these conditions. Using dimensional measures of psychopathology, we examined whether comorbid symptoms influence the association of ADHD symptoms with daily cortisol output. METHODS: 138 adolescents (ages 11-15 years) completed measures of symptoms of psychopathology and provided saliva samples over two days. We analyzed whether ADHD symptoms were related to morning, afternoon, and evening cortisol, the cortisol awakening response (CAR) and cumulative daily cortisol (area under the curve with respect to ground [AUCg]) while accounting for symptoms of three psychiatric disorders that are commonly comorbid with ADHD: conduct disorder (CD), anxiety, and depression. In sensitivity analyses, we included symptoms of oppositional defiant disorder (ODD) in place of CD symptoms. FINDINGS: After controlling for symptoms of CD, anxiety, and depression, ADHD symptoms were associated significantly with higher cumulative diurnal cortisol (AUCg), morning cortisol, and afternoon cortisol. Symptoms of CD, anxiety and depression were not associated significantly with any cortisol metrics; however, in sensitivity analyses, ODD symptoms were associated with lower AUCg and morning cortisol. DISCUSSION: Our findings highlight the distinct influence of ADHD and externalizing symptoms on cortisol output. Further work is needed to examine the specificity of altered HPA-axis activity as a biomarker of ADHD and to elucidate whether symptoms of ADHD differ in their association with diurnal cortisol as a function of their severity.

Negative caregiving and stress reactivity moderate the relation between early life stress and externalizing in adolescence.

Exposure to early life stress (ELS) is common and has been implicated in the development of psychopathology; importantly, however, many individuals who experience ELS do not develop emotional or behavioral difficulties. Prior research implicates stress exposure, negative caregiving behaviors, and patterns of physiological reactivity in predicting psychological well-being; however, the precise factors that contribute to resilience versus vulnerability to the adverse effects of stress exposures are not well understood. In a longitudinal study of adolescents (N = 120) assessed at three timepoints approximately every 2 years beginning at the ages of 913 years, we examined the roles of autonomic reactivity to social stress (assessed through skin conductance during the Trier Social Stress Task) and negative caregiving behaviors as moderators of the association between exposure to ELS and internalizing and externalizing symptoms. We found that the relation between ELS and externalizing symptoms was moderated by both negative caregiving and autonomic reactivity, such that the relation between ELS and externalizing was positive at low levels of negative caregiving and at high levels of autonomic reactivity; interactions predicting internalizing symptoms were not statistically significant. These findings highlight the importance of considering physiological and environmental variables that might contribute to susceptibility or resilience to symptoms of psychopathology following exposure to ELS.

Socioeconomic and psychological correlates of postpartum depression at 6 months in Dhaka, Bangladesh.

To current study aimed to estimate the point prevalence and identify correlates of postpartum depression (PPD) in a sample of mothers in Dhaka. A total of 235 participants from low- and middle-SES neighbourhoods in Dhaka completed the Edinburgh Postnatal Depression Scale (EPDS) and other assessments of socioeconomic and psychological factors at 24 weeks postpartum. Regression models were fit to explore potential correlates of PPD. The estimated prevalence of high PPD risk in the current sample is 24.3%. In multivariable linear regression models, recent life events, perceived stress and household resources (e.g., access to cooking gas, telephone, furniture, electricity, television, etc.) were significantly associated with PPD. The association of social support with PPD when controlling for other variables was sensitive to the choice of social support measure, highlighting an important methodological issue. The point prevalence of PPD among poor, urban mothers in Bangladesh ranges from 12.3 to 28.5%, with psychological risk factors and household resources as strong correlates.

Cumulative psychosocial risk and early child development: validation and use of the Childhood Psychosocial Adversity Scale in global health research.

BACKGROUND: Evidence suggests that cumulative early psychosocial adversity can influence early child development (ECD). The Childhood Psychosocial Adversity Scale (CPAS) is a novel measure of cumulative risk designed for use in global ECD research. We describe its development and assess validity from its first application in Bangladesh, where it predicts cognitive development scores among young children. METHODS: Items were generated from literature review and qualitatively assessed for local relevance. Two-hundred and eighty-five mother-child dyads from an urban slum of Dhaka completed the CPAS at child ages 18, 24, 48, and/or 60 months. The CPAS was assessed for internal consistency, retest reliability, and convergent, incremental, and predictive validity. RESULTS: The CPAS includes subscales assessing child maltreatment, caregiver mental health, family conflict, domestic violence, and household/community psychosocial risks. In Bangladesh, subscales had good internal consistency (Cronbach's α > 0.70). Full-scale score had good 2-week test-retest reliability (intra-class correlation coefficient = 0.89; F(38,38) = 8.45, p < 0.001). Using multivariate regression, 48-month CPAS score significantly predicted 60-month intelligence quotient, accounting for more variance than socioeconomic status or malnutrition. CONCLUSIONS: The CPAS is a novel tool assessing cumulative childhood psychosocial risk. Evidence supports validity of its use in ECD research in Bangladesh, and ongoing work is applying it in additional countries.

Biological embedding of childhood adversity: from physiological mechanisms to clinical implications.

BACKGROUND: Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes "biologically embedded" in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence. OBSERVATIONS: Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course. CONCLUSIONS: Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies.

Effects of poverty on interacting biological systems underlying child development.

The developmental sequelae of childhood poverty are well documented. However, it is not poverty per se, but a multitude of risk factors associated with poverty that have a deleterious effect on children's development. Key risks factors that are likely to contribute to the adverse developmental effects of poverty include, for instance, food insecurity, infectious disease, and psychological stress related to the child's rearing environment. In this Review, we highlight synergistic biological pathways through which co-occurring risks related to poverty interact to shape children's neurocognitive development. We focus on pathways related to neural growth, energy metabolism, inflammation, and neuroendocrine responses to stress as key biological axes through which poverty becomes biologically embedded and might have long-term effects on children's neurocognitive development. We also discuss how biomarkers targeting these axes can be used to advance research on the biological processes through which poverty affects children's cognitive outcomes. Although the discussion has global relevance, we focus on low-resource settings where rates of poverty are highest and access to treatment might be limited.

The science of early adversity: is there a role for large institutions in the care of vulnerable children?

It has been more than 80 years since researchers in child psychiatry first documented developmental delays among children separated from family environments and placed in orphanages or other institutions. Informed by such findings, global conventions, including the 1989 UN Convention on the Rights of the Child, assert a child's right to care within a family-like environment that offers individualised support. Nevertheless, an estimated 8 million children are presently growing up in congregate care institutions. Common reasons for institutionalisation include orphaning, abandonment due to poverty, abuse in families of origin, disability, and mental illness. Although the practice remains widespread, a robust body of scientific work suggests that institutionalisation in early childhood can incur developmental damage across diverse domains. Specific deficits have been documented in areas including physical growth, cognitive function, neurodevelopment, and social-psychological health. Effects seem most pronounced when children have least access to individualised caregiving, and when deprivation coincides with early developmental sensitive periods. Offering hope, early interventions that place institutionalised children into families have afforded substantial recovery. The strength of scientific evidence imparts urgency to efforts to achieve deinstitutionalisation in global child protection sectors, and to intervene early for individual children experiencing deprivation.