Annual Research Review: The Power of Predictability – Patterns of Signals in Early Life Shape Neurodevelopment and Mental Health Trajectories

The global burden of early life adversity (ELA) is profound. The World Health Organization has estimated that ELA accounts for almost 30% of all psychiatric cases. Yet, our ability to identify which individuals exposed to ELA will develop mental illness remains poor and there is a critical need to identify underlying pathways and mechanisms. This review proposes unpredictability as an understudied aspect of ELA that is tractable and presents a conceptual model that includes biologically plausible mechanistic pathways by which unpredictability impacts the developing brain. The model is supported by a synthesis of published and new data illustrating the significant impacts of patterns of signals on child development. We begin with an overview of the existing unpredictability literature, which has focused primarily on longer patterns of unpredictability (e.g. years, months, and days). We then describe our work testing the impact of patterns of parental signals on a moment-to-moment timescale, providing evidence that patterns of these signals during sensitive windows of development influence neurocircuit formation across species and thus may be an evolutionarily conserved process that shapes the developing brain. Next, attention is drawn to emerging themes which provide a framework for future directions of research including the evaluation of functions, such as effortful control, that may be particularly vulnerable to unpredictability, sensitive periods, sex differences, cross-cultural investigations, addressing causality, and unpredictability as a pathway by which other forms of ELA impact development. Finally, we provide suggestions for prevention and intervention, including the introduction of a screening instrument for the identification of children exposed to unpredictable experiences

Children's Brain Development Benefits from Longer Gestation

Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease

The X-Trials: Neural Correlates of an Inhibitory Control Task in Children and Adults

Event-related potentials (ERPs) were used to examine developmental differences between adults and 6-year-old children in the neural processes involved in an inhibitory control task. Twenty adults and 21 children completed a task that required them to selectively respond to target stimuli while inhibiting responses to equally salient non-target stimuli. Because this task had been previously studied using functional magnetic resonance imaging (fMRI), the relation between the fMRI and ERP findings was informally examined. The results indicate that latency and amplitude of the P3 differentiated the different types of trials. However, the pattern of event-related neural activity differed for adults and children. These results, which suggest that adults and children may be using different processes to perform this task, have implications for the interpretation of the previous fMRI findings

Maternal Prenatal Cortisol Trajectories Predict Accelerated Growth in Infancy

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)2 and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers’ prenatal cortisol trajectories

DHEA: A Neglected Biological Signal That May Affect Fetal and Child Development

The stress-sensitive maternal hypothalamic–pituitary–adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study examined, for the first time, the joint impact of fetal exposure to prenatal maternal DHEA and cortisol on infant emotional reactivity. Methods Participants were 124 mother–infant dyads. DHEA and cortisol were measured from maternal hair at 15 weeks (early gestation) and 35 weeks (late gestation). Observational assessments of positive and negative emotional reactivity were obtained in the laboratory when the infants were 6 months old. Pearson correlations were used to examine the associations between prenatal maternal cortisol, prenatal maternal DHEA, and infant positive and negative emotional reactivity. Moderation analyses were conducted to investigate whether DHEA might modify the association between cortisol and emotional reactivity. Results Higher levels of both early and late gestation maternal DHEA were linked to greater infant positive emotional reactivity. Elevated late gestation maternal cortisol was associated with greater negative emotional reactivity. Finally, the association between fetal cortisol exposure and infant emotional reactivity was only observed when DHEA was low. Conclusions These new observations indicate that DHEA is a potential maternal biological signal involved in prenatal programming. It appears to act both independently and jointly with cortisol to determine a child\u27s emotional reactivity. Its role as a primary end-product of the HPA axis, coupled with the newly documented associations with prenatal development shown here, strongly calls for the inclusion of DHEA in future investigations of fetal programming

Temporal Relation Between Pubertal Development and Peer Victimization in a Prospective Sample of US Adolescents

Peer victimization typically peaks in early adolescence, leading researchers to hypothesize that pubertal timing is a meaningful predictor of peer victimization. However, previous methodological approaches have limited our ability to parse out which puberty cues are associated with peer victimization because gonadal and adrenal puberty, two independent processes, have either been conflated or adrenal puberty timing has been ignored. In addition, previous research has overlooked the possibility of reverse causality—that peer victimization might drive pubertal timing, as it has been shown to do in non-human primates. To fill these gaps, we followed 265 adolescents (47% female) prospectively across three-time points (Mage: T1 = 9.6, T2 = 12.0, T3 = 14.4) and measured self-report peer victimization and self- and maternal-report of gonadal and adrenal pubertal development on the Pubertal Development Scale. Multilevel modeling revealed that females who were further along in adrenal puberty at age 9 were more likely to report peer victimization at age 12 (Cohen\u27s d = 0.25, p = .005). The relation between gonadal puberty status and peer victimization was not significant for either sex. In terms of the reverse direction, the relation between early peer victimization and later pubertal development was not significant in either sex. Overall, our findings suggest that adrenal puberty status, but not gonadal puberty status, predicted peer victimization in females, highlighting the need to separate gonadal and adrenal pubertal processes in future studies

Patterns of Maternal Distress from Pregnancy Through Childhood Predict Psychopathology During Early Adolescence

Capitalizing on a longitudinal cohort followed from gestation through adolescence (201 mother–child dyads), we investigate the contributions of severity and stability of both maternal depressive and perceived stress symptoms to adolescent psychopathology. Maternal depressive and perceived stress trajectories from pregnancy through adolescence were identified with latent class growth analyses, and associations with adolescent internalizing and externalizing symptoms were examined. For both depression and stress, the most common trajectory group comprised mothers displaying stable and low symptom levels over time, and adolescents of these mothers had the fewest internalizing and externalizing symptoms. Maternal membership to one or more aberrant trajectory groups predicted higher levels of internalizing and externalizing symptoms, determined by both maternal and adolescent self-report. This study indicates that profiles of multiple indicators of maternal psychopathology assessed across childhood, beginning prenatally, can provide critical additional insight into child psychopathology risk

Longer Gestation Among Children Born Full Term Influences Cognitive and Motor Development

Children born preterm show persisting impairments in cognitive functioning, school achievement, and brain development. Most research has focused on implications of birth prior to 37 gestational weeks; however, the fetal central nervous system continues to make fundamental changes throughout gestation. Longer gestation is associated with reduced morbidity and mortality even among infants born during the period clinically defined as full term (37–41 gestational weeks). The implications of shortened gestation among term infants for neurodevelopment are poorly understood. The present study prospectively evaluates 232 mothers and their full term infants (50.4% male infants) at three time points across the first postnatal year. We evaluate the association between gestational length and cognitive and motor development. Infants included in the study were full term (born between 37 and 41 weeks gestation). The present study uses the combination of Last Menstrual Period (LMP) and early ultrasound for accurate gestational dating. Hierarchical Linear Regression analyses revealed that longer gestational length is associated with higher scores on the Bayley scales of mental and motor development at 3, 6 and 12 months of age after considering socio-demographic, pregnancy, and infant-level covariates. Findings were identical using revised categories of early, term, and late term proposed by the Working Group for Defining Term Pregnancy. Our findings indicate that longer gestation, even among term infants, benefits both cognitive and motor development

Cesarean Delivery and Infant Cortisol Regulation

Background: Cesarean delivery reduces the risk of infant and maternal morbidity and mortality when medically indicated, however, the cesarean delivery rate is estimated to be two to three times higher than medically necessary. The World Health Organization and American College of Obstetricians and Gynecologists have expressed concern over the high rates of cesarean delivery, citing evidence that cesarean delivery has negative short- and long-term consequences for the health of the infant, mother, and for future pregnancies. Infants delivered by cesarean are at an increased risk of metabolic disease and immune dysfunction throughout the lifespan. Preliminary research suggests that the hypothalamic pituitary adrenal (HPA) axis is a plausible pathway linking cesarean delivery to poor health later in life. The present study examines the relation between mode of delivery and HPA axis function in six-month-old infants. We also examine whether the cesarean delivery was elective or indicated altered to the relation between mode of delivery and infant cortisol profiles. Methods: The sample included 136 mother/infant pairs. Thirty-nine women delivered by cesarean and 97 delivered vaginally. Maternal and infant medical records were reviewed for prenatal medical history and birth outcomes. Infant saliva was collected for cortisol analysis at a 6-month well-baby checkup. Samples were collected upon arrival to the appointment (baseline) and 20 min after exposure to a painful stressor, the inoculation procedure (response). A mixed model ANCOVA was conducted to determine whether salivary cortisol concentrations differed between the two delivery groups. To examine whether complications related to having an indicated cesarean delivery contributed to any association between mode of delivery and cortisol production, cortisol concentrations were compared between the subgroup of infants whose cesarean deliveries were elective (e.g. maternal request or previous cesarean delivery) to infants delivered vaginally. Results: Infants delivered by cesarean had lower cortisol concentrations at baseline and after the inoculation procedure compared to those delivered vaginally. Further, the relation between mode of delivery and cortisol levels persisted even when the analyses were restricted to compare only the elective cesarean deliveries (e.g. maternal request or previous cesarean delivery) to those delivered vaginally. Discussion: This study provides evidence for an association between cesarean delivery and infant HPA axis function in infancy. Findings are consistent with the hypothesis that the HPA axis is a plausible pathway that links cesarean delivery with long-term health outcomes

Experiences of COVID-19-Related Racism and Impact on Depression Trajectories Among Racially/Ethnically Minoritized Adolescents

Purpose In 2020, racially/ethnically minoritized (REMD) youth faced the “dual pandemics” of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic). Methods A community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%). Results REMD adolescents\u27 depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date. Discussion REMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth