The future of intergenerational transmission research: A prospective, three-generation approach.

Dr. Dante Cicchetti's pioneering theory and research on developmental psychopathology have been fundamental to the proliferation of research on intergenerational transmission over the last 40 years. In part due to this foundation, much has been learned about continuities and discontinuities in child maltreatment, attachment, parenting, and psychopathology across generations. Looking towards the future, we propose that this field stands to benefit from a prospective, three-generation approach. Specifically, following established prospective, longitudinal cohorts of children over their transition to parenting the next generation will afford the opportunity to investigate the developmental origins of intergenerational transmission. This approach also can address key outstanding questions and methodological limitations in the extant literature related to the confounding of retrospective and prospective measures; examination of mediators and moderators; and investigation of the roles of biology, environment, and their interplay. After considering these advantages, we offer several considerations and recommendations for future research, many of which are broadly applicable to the study of two or more generations. We hope that this discussion will inspire the leveraging of existing prospective cohorts to carry forward Dr. Cicchetti's remarkable contributions, with the ultimate aim to inform the development of preventions and interventions that disrupt deleterious intergenerational cycles.

Recalibration of the stress response system over adult development: Is there a perinatal recalibration period?

During early life-sensitive periods (i.e., fetal, infancy), the developing stress response system adaptively calibrates to match environmental conditions, whether harsh or supportive. Recent evidence suggests that puberty is another window when the stress system is open to recalibration if environmental conditions have shifted significantly. Whether additional periods of recalibration exist in adulthood remains to be established. The present paper draws parallels between childhood (re)calibration periods and the perinatal period to hypothesize that this phase may be an additional window of stress recalibration in adult life. Specifically, the perinatal period (defined here to include pregnancy, lactation, and early parenthood) is also a developmental switch point characterized by heightened neural plasticity and marked changes in stress system function. After discussing these similarities, lines of empirical evidence needed to substantiate the perinatal stress recalibration hypothesis are proposed, and existing research support is reviewed. Complexities and challenges related to delineating the boundaries of perinatal stress recalibration and empirically testing this hypothesis are discussed, as well as possibilities for future multidisciplinary research. In the theme of this special issue, perinatal stress recalibration may be a mechanism of multilevel, multisystem risk, and resilience, both intra-individually and intergenerationally, with implications for optimizing interventions.

Calibration and recalibration of stress response systems across development: Implications for mental and physical health.

Decades of human and animal research demonstrates that stress responsive neuroendocrine systems calibrate to the harshness of environmental conditions during fetal and early postnatal life. Emerging evidence indicates that if conditions change markedly over childhood, the hypothalamic pituitary adrenal (HPA) axis may recalibrate during puberty, another period that involves heightened neural plasticity and rapid maturation of neurobehavioral systems. These recent findings have prompted increased interest in the potential for stress system calibration/recalibration over development. To direct research in this area, this chapter integrates and discusses theoretical perspectives and empirical evidence pertaining to calibration and recalibration of the stress response. We describe how these concepts relate to other constructs, including sensitive periods, plasticity, and programming. We then consider four potential periods of calibration/recalibration: fetal, infancy, puberty, and pregnancy/lactation. In each section, we discuss evidence that the HPA and/or sympathetic medullary adrenal (SAM) system undergoes developmental change, rendering it more plastic and amenable to shift its activity in response to environmental conditions. We also review findings that the impacts of environmental harshness on stress responding persist beyond these periods. We then articulate that marked change in the quality of the environment (from harsh to benign or vice versa) is required in order for recalibration to occur, and that recalibration would result in shifts in stress responding to more closely align with the profiles of individuals who have experienced these conditions throughout life. Finally, we reflect on whether recalibration of the HPA and SAM system may extend to the other stress-responsive neurobehavioral systems.

Maternal Psychological Distress and Lactation and Breastfeeding Outcomes: a Narrative Review.

PURPOSE: Despite recommendations from the World Health Organization and the American Academy of Pediatrics to exclusively breastfeed infants for their first 6 months of life, 75% of women do not meet exclusive breastfeeding guidelines, and 60% do not meet their own breastfeeding goals. Numerous observational studies have linked maternal psychological distress (eg, perceived stress, anxiety, and depression) with nonoptimal breastfeeding outcomes, such as decreased proportion and duration of exclusive breastfeeding. The physiological mechanisms underlying these associations, however, remain unclear. METHODS: For this narrative review, we evaluated the evidence of relationships between maternal psychological distress and lactation and breastfeeding outcomes in pregnancy and post partum and the possible physiological mechanisms that facilitate these relationships. We searched PubMed using the following terms: stress, anxiety, depression, breastfeeding, and lactation. Additional search by hand was conducted to ensure a thorough review of the literature. FINDINGS: Among the studies examined, methods used to assess maternal psychological distress were not uniform, with some studies examining perceived distress via a variety of validated tools and others measuring biological measures of distress, such as cortisol. Evidence supports a role for psychological distress in multiple breastfeeding outcomes, including delayed secretory activation and decreased duration of exclusive breastfeeding. One physiological mechanism proposed to explain these relationships is that psychological distress may impair the release of oxytocin, a hormone that plays a critical role in milk ejection during lactation. Continued impairment of milk ejection may lead to decreased milk production because of incomplete emptying of the breast during each feed. Maternal distress may also yield elevated levels of serum cortisol and decreased insulin sensitivity, which are associated with decreased milk production. The relationship between psychological distress and breastfeeding is likely to be bidirectional, however, in that breastfeeding appears to reduce maternal distress, again possibly via effects on the pleasure or reward pathway and calming effects of oxytocin on the mother. This finding suggests that interventions to support lactation and breastfeeding goals in women who score high on measures of psychological distress would be beneficial for both maternal and infant well-being. IMPLICATIONS: Evidence to date suggests that maternal psychological distress may impair lactation and breastfeeding outcomes, but stronger study designs and rigorous assessment methods are needed. A better understanding of the physiological mechanisms leading to impaired lactation may assist in the development of early interventions for mothers experiencing distress. In addition, stress-reducing programs and policies should be investigated for their potential to improve breastfeeding outcomes.

Depressive Symptoms among Pregnant and Postpartum Women in Prison.

INTRODUCTION: Women in prison experience high rates of mental and physical health problems, and pregnant and postpartum women in prison may be particularly vulnerable. Very few studies have examined depressive symptoms among women who are pregnant and give birth in prison. We assessed depressive symptoms longitudinally from pregnancy into the postpartum period in a sample of 58 women who gave birth in prison. We also considered whether incarceration-related factors (length of time incarcerated while pregnant, remaining length of sentence to serve after birth) were associated with depressive symptoms. METHODS: Data were collected as part of an ongoing evaluation of a prison-based pregnancy and parenting support program at one women's state prison. At prenatal and postpartum visits with their doula, women completed the Patient Health Questionnaire-9 (PHQ-9), a measure of depressive symptom severity. RESULTS: More than one-third of our sample of women who were incarcerated and gave birth in custody met criteria for moderate to severe depression on the PHQ-9 during pregnancy or the postpartum period. Women who faced longer periods of incarceration following birth and separation from their newborns reported higher levels of postpartum depressive symptoms. DISCUSSION: Findings have implications for practice and policy aimed at supporting the mental health needs of women who are pregnant in prison, particularly those women who give birth in custody and are separated from their newborns.

Prenatal maternal mood entropy is associated with child neurodevelopment.

Emerging evidence indicates that the predictability of signals early in life may influence the developing brain. This study examines links between a novel indicator of maternal mood dysregulation, mood entropy, and child neurodevelopmental outcomes. Associations between prenatal maternal mood entropy and child neurodevelopment were assessed in 2 longitudinal cohorts. Maternal mood was measured several times over pregnancy beginning as early as 15 weeks' gestation. Shannon's mood entropy was applied to distributions of mothers' responses on mood questionnaires. Child cognitive and language development were evaluated at 2 and 6-9 years of age. Higher prenatal maternal mood entropy was associated with lower cognitive development scores at 2 years of age and lower expressive language scores at 6-9 years of age. These associations persisted after adjusting for maternal pre and postnatal mood levels and for other relevant sociodemographic factors. Our findings identify maternal mood entropy as a novel predictor of child neurodevelopment. Characterizing components of maternal mood in addition to level of severity or valence may further our understanding of specific processes by which maternal mood shapes child development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Pubertal recalibration of cortisol-DHEA coupling in previously-institutionalized children.

As a period of heightened plasticity, puberty may provide a window of opportunity for recalibration of the hypothalamic-pituitary-adrenal (HPA) axis to current conditions. Our group has recently documented evidence for pubertal recalibration of HPA axis reactivity among children internationally adopted as infants from institutions into supportive, well-resourced homes. As a first step at examining potential mechanisms by which puberty may facilitate recalibration of the HPA axis, the current study assessed whether previously-institutionalized (PI) children differed from non-adopted (NA) comparison children in levels of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and in its intra-individual covariation (coupling) with cortisol by adrenal pubertal stage. In an accelerated longitudinal design, 7- to 15-year-olds completed up to 3 annual assessments, which included nurse-conducted pubertal staging and the Modified Trier Social Stress Test for Children (TSST-M). Adrenal (pubic hair) rather than gonadal pubertal stage scores were used in the analysis. Paired salivary cortisol-DHEA samples were available at 60-80 min post-TSST-M. NA and PI children did not differ in DHEA levels, which were higher among children at more advanced pubertal stages (averaged across the sessions) for both groups. For NA children, post-stressor cortisol and DHEA were positively coupled across sessions at all average adrenal pubertal stages. For PI children who were, on average, at earlier adrenal pubertal stages, post-stressor cortisol and DHEA were not coupled, but PI children who were at later pubertal stages demonstrated positive cortisol-DHEA coupling similar to that of the NA children. We suggest that these findings provide insights into processes which may underlie pubertal recalibration of the HPA axis.

Prenatal maternal psychological distress and fetal developmental trajectories: associations with infant temperament.

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal-fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life.

Prenatal Risk for ASD: Fetal Cortisol Exposure Predicts Child Autism-Spectrum Disorder Symptoms.

The etiology of autism spectrum disorder (ASD) is multifactorial and complex and likely involves interactions among genetic, epigenetic and environmental factors. With respect to environmental influences, a growing literature implicates intrauterine experiences in the origin of this pervasive developmental disorder. In this prospective longitudinal design, we examine the hypothesis that fetal exposure to maternal cortisol may confer ASD risk. In addition, because ASD is four times more prevalent in males than females and because sexually dimorphic responses to intrauterine experiences are commonly observed, we examine whether or not any associations differ by fetal sex. Maternal plasma cortisol was measured at 15, 19, 25, 31, and 37 weeks' gestation in a sample of 84 pregnant women. ASD symptoms were assessed in their 5-year old children with the Social Communication Questionnaire (SCQ). Fetal exposure to lower levels of maternal cortisol was associated with higher levels of ASD symptoms among boys only. The observed hypocortisolemic profile exhibited by these mothers may indicate a risk factor that precedes the stress of caregiving for a child with ASD and may not be solely a consequence of the stress of caregiving as previously thought. Further, these findings confirm the value of examining prenatal hormone exposures as predictors of ASD risk and support the premise that altered prenatal steroid exposures may play a role in the etiology of ASD.

Parental criticism and behavior problems in children with autism spectrum disorder.

Associations between parent critical attitudes (a component of the Expressed Emotion construct) and behavior problems have been relatively well established in adolescents and young adults with autism spectrum disorder, but use of systems adapted for children with autism spectrum disorder and additional investigations with younger samples are needed. This study examined parental criticism, derived from a population-specific coding system, as related to behavior problems in children with autism spectrum disorder between the ages of 4 and 11 years, and considered parental warmth and children's psychophysiological reactivity as statistical moderators of these associations. In all, 40 children with autism spectrum disorder and their primary caregivers attended a visit involving collection of child electrodermal activity, parent-child interaction, a parent interview from which critical attitudes and warmth were coded, and parent report of child behavior problems. Criticism was directly related to higher child externalizing but not internalizing problems. Parental criticism interacted with warmth in the prediction of internalizing problems such that criticism was only associated with more problems in the context of moderate but not high warmth. Criticism was positively associated with externalizing problems under conditions of moderate and high, but not low, child electrodermal activity reactivity. Implications for conceptualizations of parental criticism in autism spectrum disorder, for understanding comorbid behavior problems in this population, and for intervention are discussed.

Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood.

Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test-retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness.

Maternal programming: Application of a developmental psychopathology perspective.

The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes of signaling that are available to the fetus to affect maternal phenotypes (hormones, motor activity, and gene transfer) and also illustrate how evolutionary perspectives can help explain how and why fetal functions may contribute to maternal psychopathology. The developmental psychopathology perspective has spurred advances in understanding risk and resilience for mental health in many domains. As such, it is surprising that this major epoch in the female life span has yet to benefit fully from similar applications.

Prenatal maternal mood patterns predict child temperament and adolescent mental health.

BACKGROUND: This study quantifies the dynamics of maternal mood focusing on unpredictability, and to assess if greater unpredictability of prenatal maternal mood predicts child temperament and internalizing symptoms through early adolescence. METHODS: The association between prenatal mood predictability and child internalizing symptoms were assessed in two longitudinal cohorts (N's = 227 and 180). Maternal mood was assessed repeatedly during pregnancy as early as 15 weeks' gestation. Predictability of maternal mood was calculated by applying Shannon's entropy to the distribution of responses on mood questionnaires. Maternal reports of child negative affectivity (a predictor of later internalizing) were collected at 6, 12, 24 months and 7 years of age. Child self-reports of anxiety symptoms were collected at 10 years and reports of depression symptoms at 13 years. RESULTS: Fetal exposure to more elevated maternal mood entropy predicted higher levels of child negative affectivity at 12 months (r = .36; p < 01), 24 months (r = .31; p < 01) and 7 years (r = .32; p < 01) of age. In addition, children exposed to higher prenatal maternal mood entropy, reported higher levels of anxiety symptoms at 10 years (r = .24; p < 01) and elevated depressive symptoms at 13 years (r = .29; p < .01). These associations persisted after adjusting for maternal pre and postnatal mood valence (e.g. depression levels) and for other relevant demographic characteristics. CONCLUSIONS: Our findings provide strong support for the notion that patterns of maternal mood influence the developing brain. More specifically, they suggest that prenatal maternal mood predictability may be a critical predictor of developmental mental health trajectories and should be considered when assessing early life influences on lifespan mental health.

Sympathetic Under-Arousal and Externalizing Behavior Problems in Children with Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) commonly exhibit co-occurring externalizing behavior problems, which can impede learning opportunities and contribute significantly to caregiver stress. Substantial theory and research has linked under-arousal of the sympathetic nervous system to increased externalizing problems in children without ASD, but under-arousal has not been considered as an explanatory mechanism for individual differences among children with ASD. We tested the notion that lower electrodermal activity (EDA) would predict more externalizing problems in children with ASD, and considered the degree to which parent co-regulatory support could buffer this risk. Forty children with ASD between the ages of 4 and 11 years and their primary caregivers participated in a laboratory visit that included various play, compliance, and problem-solving regulatory tasks. EDA was measured through wireless wrist sensors, parental scaffolding was observed during a dyadic problem-solving task, and parents rated their children's externalizing behavior problems. As predicted, low EDA during the compliance-oriented tasks directly predicted higher child externalizing problems. Parental scaffolding moderated the link between under-arousal during the problem-solving regulatory tasks and externalizing problems such that the relation was observed in the context of low, but not high, support. Implications for relevant theories (e.g., fearlessness theory, stimulation-seeking theory) are discussed, and the potential for psychophysiological patterns to inform intervention with these children is considered.

Electrodermal Variability and Symptom Severity in Children with Autism Spectrum Disorder.

Associations between variability in sympathetic nervous system arousal and individual differences in symptom severity were examined for children with autism spectrum disorder (ASD). Thirty-four families participated in a laboratory visit that included continuous measurement of electrodermal activity (EDA) during a battery of naturalistic and structured parent-child, child alone, and direct testing tasks. Multiple indices of EDA were considered. Greater variability in EDA was associated with higher levels of ASD symptoms, with findings generally consistent across tasks. Intellectual functioning did not moderate the relation between EDA and ASD symptoms. Sympathetic arousal tendencies may represent an important individual difference factor for this population. Future directions and conceptualizations of EDA are discussed.

Developmental origins of the human hypothalamic-pituitary-adrenal axis.

INTRODUCTION: The developmental origins of disease or fetal programming model predicts that intrauterine exposures have life long consequences for physical and psychological health. Prenatal programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis is proposed as a primary mechanism by which early experiences are linked to later disease risk. Areas covered: This review describes the development of the fetal HPA axis, which is determined by an intricately timed cascade of endocrine events during gestation and is regulated by an integrated maternal-placental-fetal steroidogenic unit. Mechanisms by which stress-induced elevations in hormones of maternal, fetal, or placental origin influence the structure and function of the emerging fetal HPA axis are discussed. Recent prospective studies documenting persisting associations between prenatal stress exposures and altered postnatal HPA axis function are summarized, with effects observed beginning in infancy into adulthood. Expert commentary: The results of these studies are synthesized, and potential moderating factors are discussed. Promising areas of further research highlighted include epigenetic mechanisms and interactions between pre and postnatal influences.

Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms.

OBJECTIVE: Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5. METHOD: Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks' gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview. RESULTS: Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self-reported internalizing symptoms. CONCLUSIONS: Findings suggest that elevated exposures to the feto-placental stress signal pCRH exert programming effects on the developing fetal central nervous system, with lasting consequences for child mental health.

Brief Report: A Pilot Study of Parent-Child Biobehavioral Synchrony in Autism Spectrum Disorder.

The theory of biobehavioral synchrony proposes that the predictive power of parent-child attunement likely lies in the manner with which behaviors are aligned with relevant biological processes. Symptoms of autism spectrum disorder (ASD) may challenge the formation of behavioral and physiological synchrony, but maintenance of such parent-child attunement could prove beneficial. The present study is the first to examine parent-child physiological synchrony in ASD. Parent and child electrodermal activity (EDA) was measured continuously during naturalistic free play. Parent-child EDA synchrony (positive covariation) was positively correlated with observed parent-child emotional attunement. Hierarchical linear modeling revealed that child ASD symptoms moderated the association between parent EDA and child EDA, such that EDA synchrony was stronger for children with lower ASD symptom levels.