Andrew S. Garner

The lifelong effects of early childhood adversity and toxic stress

Advances in fields of inquiry as diverse as neuroscience, molecular biology, genomics, developmental psychology, epidemiology, sociology, and economics are catalyzing an important paradigm shift in our understanding of health and disease across the lifespan. This converging, multidisciplinary science of human development has profound implications for our ability to enhance the life prospects of children and to strengthen the social and economic fabric of society. Drawing on these multiple streams of investigation, this report presents an ecobiodevelopmental framework that illustrates how early experiences and environmental influences can leave a lasting signature on the genetic predispositions that affect emerging brain architecture and long-term health. The report also examines extensive evidence of the disruptive impacts of toxic stress, offering intriguing insights into causal mechanisms that link early adversity to later impairments in learning, behavior, and both physical and mental well-being. The implications of this framework for the practice of medicine, in general, and pediatrics, specifically, are potentially transformational. They suggest that many adult diseases should be viewed as developmental disorders that begin early in life and that persistent health disparities associated with poverty, discrimination, or maltreatment could be reduced by the alleviation of toxic stress in childhood. An ecobiodevelopmental framework also underscores the need for new thinking about the focus and boundaries of pediatric practice. It calls for pediatricians to serve as both front-line guardians of healthy child development and strategically positioned, community leaders to inform new science-based strategies that build strong foundations for educational achievement, economic productivity, responsible citizenship, and lifelong health.

Early Childhood Adversity, Toxic Stress, and the Role of the Pediatrician: Translating Developmental Science Into Lifelong Health

Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community—one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters—to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

Isoforms of the avian TrkC receptor: A novel kinase insertion dissociates transformation and process outgrowth from survival

TrkC receptor isoforms have been identified by cDNA cloning and RT-PCR analysis of embryonic chick brain RNA. An N-terminal truncation motif is missing from the signal sequence and first cysteine cluster of the extracellular domain. Within the cytoplasmic dimain, a kinase truncation motif retains part of the kinase domain, but appeared to lack activity. Finally, a kinase insert (KI) motif introduces a 25 amino acid sequence distinct from the known mammalian inserts. KI receptors, like full-length receptors, were tyrosine phosphorylated in response to NT-3 and mediated the transformation of chick embryo fibroblasts and process outgrowth from rat PC12 cells. However, KI receptors supported little, if any, survival of serum-deprived PC12 cells. These results indicate that alternative splicing of trkC transcripts is an important mechanism for regulating cellular responses to NT-3.

Home visiting and the biology of toxic stress: opportunities to address early childhood adversity.

Home visiting is an important mechanism for minimizing the lifelong effects of early childhood adversity. To do so, it must be informed by the biology of early brain and child development. Advances in neuroscience, epigenetics, and the physiology of stress are revealing the biological mechanisms underlying well-established associations between early childhood adversity and suboptimal life-course trajectories. Left unchecked, mediators of physiologic stress become toxic, alter both genome and brain, and lead to a vicious cycle of chronic stress. This so-called “toxic stress” results a wide array of behavioral attempts to blunt the stress response, a process known as “behavioral allostasis.” Although behaviors like smoking, overeating, promiscuity, and substance abuse decrease stress transiently, over time they become maladaptive and result in the unhealthy lifestyles and noncommunicable diseases that are the leading causes of morbidity and mortality. The biology of toxic stress and the concept of behavioral allostasis shed new light on the developmental origins of lifelong disease and highlight opportunities for early intervention and prevention. Future efforts to minimize the effects of childhood adversity should focus on expanding the capacity of caregivers and communities to promote (1) the safe, stable, and nurturing relationships that buffer toxic stress, and (2) the rudimentary but foundational social-emotional, language, and cognitive skills needed to develop healthy, adaptive coping skills. Building these critical caregiver and community capacities will require a public health approach with unprecedented levels of collaboration and coordination between the healthcare, childcare, early education, early intervention, and home visiting sectors.

Translating Developmental Science to Address Childhood Adversity.

Demystifying child development is a defining element of pediatric care, and pediatricians have long appreciated the profound influences that families and communities have on both child development and life course trajectories. Dramatic advances in the basic sciences of development are beginning to reveal the biologic mechanisms underlying well-established associations between a spectrum of childhood adversities and less than optimal outcomes in health, education and economic productivity. Pediatricians are well positioned to translate this new knowledge into both practice and policy, but doing so will require unprecedented levels of collaboration with educators, social service providers, and policy makers. Pediatricians might recognize the negative impact of family-level adversities on child development, but developing an effective response will likely require the engagement of community partners. By developing collaborative, innovative ways to promote the safe, stable, and nurturing relationships that are biologic prerequisites for health, academic success, and economic productivity, family-centered pediatric medical homes will remain relevant in an era that increasingly values wellness and population health.

Identifying Maternal Depression in Pediatric Primary Care: Changes Over a Decade.

Objective: Maternal depression affects 10% to 40% of mothers with young children and has negative consequences for childrens health and development. The American Academy of Pediatrics (AAP) recommends that pediatricians identify women with maternal depression. The authors examined trends in inquiring about (asking informal questions) or screening for (using a standardized instrument) maternal depression by pediatricians in 2004 and 2013 and identified correlates of usually inquiring/screening to identify maternal depression. Methods: Data were ascertained from 778 nontrainee pediatricians exclusively practicing general pediatrics who completed the 2004 (n = 457) and 2013 (n = 321) AAP Periodic Surveys. Pediatricians answered questions about physician and practice characteristics, training, attitudes, and inquiring/screening to identify maternal depression. Sample weights were used to reduce nonresponse bias. Weighted descriptive and logistic regression analyses were conducted. Results: The prevalence of usually inquiring/screening to identify maternal depression increased from 33% to 44% (p < .01). In both years, pediatricians who usually inquired about child/adolescent depression had increased odds of usually inquiring/screening to identify maternal depression. Patient race/ethnicity and training in adult Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for depression were associated with inquiring/screening in 2004, and believing that family screening is within the scope of the pediatrician was associated with inquiring/screening in 2013. Conclusion: Although inquiring/screening about maternal depression has increased since 2004, less than half of pediatricians usually screen or inquire about maternal depression, representing a missed opportunity to identify depression and manage or refer women for treatment. Further training on the importance of mental and family health to childrens health may increase identification of maternal depression in pediatric primary care.

No Technological Innovation Is a Panacea: A Case Series in Quality Improvement for Primary Care Mental Health Services:

Evaluations of quality improvement efforts targeted at mental health services in primary care pediatrics are rare. We evaluated a short-targeted educational session, a Web-based system, the Child Health and Development Interactive System, and a local area mental health services resource guide. Most physicians believed the information in the educational session was at least somewhat likely to change their practice. However, only 9.2% of the families invited to complete the Web-based system did so. Physicians found access to the Web-based system time consuming and, because the billing code for the screening activity was carved out of most of Ohios privately-insured contract, physicians received no reimbursement for the screenings. Physicians were unenthusiastic about the local resource guide because the resources were not rated for quality. This quality improvement effort demonstrates that there are not easy solutions to practice change and highlights the need for implementation support when introducing new technology.

Use of Selective Serotonin Reuptake Inhibitors by Pediatricians:: Comparing Attitudes of Primary Care Pediatricians and Child and Adolescent Psychiatrists

To compare attitudes regarding a pediatricians role in prescribing selective serotonin reuptake inhibitors for children and adolescents, surveys were mailed to 338 primary care pediatricians and 75 child and adolescent psychiatrists; half responded. Child and adolescent psychiatrists were significantly more likely than primary care pediatricians to agree that selective serotonin reuptake inhibitors are safe and effective when used for children and adolescents. Primary care pediatricians were significantly more likely than child and adolescent psychiatrists to agree that black box warnings have changed their prescribing practices. Both had similar beliefs about whether antidepressants should be prescribed only by psychiatrists and whether pediatricians should initiate selective serotonin reuptake inhibitor therapy, without or after consulting a psychiatrist. These data suggest that among child and adolescent psychiatrists and primary care pediatricians, agreement about the pediatricians role in using selective serotonin reuptake inhibitors therapy is lacking. Strategies that enhance communication and endorse support for defined roles of primary care pediatricians and child and adolescent psychiatrists will ensure that children with mental health needs are treated safely and appropriately.

Does Length of Developmental Behavioral Pediatrics Training Matter

OBJECTIVE Since 1997 pediatric residencies have been required to provide a 4-week block rotation in developmental and behavioral pediatrics (DBP), but it is not known whether this has altered the care and management of children by practicing pediatricians. The objective of this study was to compare the self-reported practice patterns of pediatricians who were trained with 4 or more weeks of DBP with the practice patterns of those who were trained for <4 weeks. METHODS We used self-reported practices from the American Academy of Pediatrics Periodic Survey 85. Pediatricians were asked whether they never, sometimes, or usually inquired about and screened for, and whether they treated/managed/comanaged attention deficit hyperactivity disorder, depression, anxiety, behavior problems and learning problems. They were also asked about a series of barriers to care. Analyses were weighted to account for low response rates. RESULTS Those with more DBP training were significantly more likely to treat/manage/co-manage depression, anxiety, behavior problems and learning problems, but were still doing so less than one third of the time. There were no differences in the care of patients with attention deficit hyperactivity disorder or in screening or inquiring about mental health conditions. Those with more training were more likely to perceive somewhat fewer barriers and to report more specific familiarity with some Diagnostic and Statistical Manual of Mental Disorders criteria and some treatment modalities. CONCLUSIONS Longer length of training is associated with more treatment, but significant deficits in self-reported practice remain, leaving much room for additional improvement in the training of clinicians in DBP.

Thinking Developmentally: The Next Evolution in Models of Health.

ABSTRACT: As the basic sciences that inform conceptions of human health advance, so must the models that are used to frame additional research, to teach the next generation of providers, and to inform health policy. This article briefly reviews the evolution from a biomedical model to a biopsychosocial (BPS) model and to an ecobiodevelopmental (EBD) model. Like the BPS model, the EBD model reaffirms the biological significance of psychosocial features within the patients ecology, but it does so at the molecular and cellular levels. More importantly, the EBD model adds the dimension of time, forcing providers to “think developmentally” and to acknowledge the considerable biological and psychological consequences of previous experiences. For the health care system to move from a reactive “sick care” system to a proactive “well care” system, all providers must begin thinking developmentally by acknowledging the dynamic but cumulative dance between nature and nurture that drives development, behavior, and health, not only in childhood, but across the lifespan.