Search

Preconception and prenatal stress impact fetal and infant development, and women of color are disproportionately exposed to sociocultural stressors like discrimination and acculturative stress. However, few studies examine links between mothers’ exposure to these stressors and offspring mental health, or possible mitigating factors. Using linear regression, we tested associations between prenatally assessed maternal acculturative stress and discrimination on infant negative emotionality among 113 Latinx/Hispanic, Asian American, Black, and Multiethnic mothers and their children. Additionally, we tested interactions between stressors and potential pre- and postnatal resilience-promoting factors: community cohesion, social support, communalism, and parenting self-efficacy. Discrimination and acculturative stress were related to more infant negative emotionality at approximately 12 months old (M = 12.6, SD = .75). In contrast, maternal report of parenting self-efficacy when infants were 6 months old was related to lower levels of infant negative emotionality. Further, higher levels of parenting self-efficacy mitigated the relation between acculturative stress and negative emotionality. Preconception and prenatal exposure to sociocultural stress may be a risk factor for poor offspring mental health. Maternal and child health researchers, policymakers, and practitioners should prioritize further understanding these relations, reducing exposure to sociocultural stressors, and promoting resilience.

PurposeIn 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).MethodsA 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%).ResultsREMD adolescents' 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.DiscussionREMD 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.

Children exposed to prenatal maternal psychological distress are at elevated risk for a range of adverse outcomes; however, it remains poorly understood whether postnatal influences can ameliorate impairments related to prenatal distress. The current study evaluated if sensitivematernal care during the first postnatal year could mitigate child cognitive and emotional impairments associated with prenatal psychological distress. Prenatal maternal psychological distress was assessed via self-reports of anxiety, depression, and perceived stress for 136 mothers at five prenatal and four postpartum time points. Quality of maternal care (sensitivity to nondistress, positive regard, and intrusiveness reverse-scored) were assessed during a mother–child play interaction at 6 and 12 months. Child cognitive function and negative emotionality were assessed at 2 years, using The Bayley Scales and the Early Childhood Behavior Questionnaire. Elevated prenatal distress was associated with poorer child cognitive function and elevated negative emotionality. Children exposed to elevated prenatal maternal distress did not, however, display these outcomes if they received high-quality caregiving. Specifically, maternal care moderated the relation between prenatal psychological distress and child cognitive function and negative emotionality. This association remained after consideration of postnatal maternal psychological distress and relevant covariates. Sensitive maternal care was associated with altered offspring developmental trajectories, supporting child resilience following prenatal distress exposure.

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

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)

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother–child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe–prefrontal cortex circuit. Infant exposure to unpredictable maternal sensory signals was assessed at 6 and 12 months. Using high angular resolution diffusion imaging, we quantified the integrity of the uncinate fasciculus using generalized fractional anisotropy (GFA). Higher maternal unpredictability during infancy presaged greater uncinate fasciculus GFA in children 9–11 years of age (n= 69, 29 female). In contrast to the uncinate, GFA of a second corticolimbic projection, the hippocampal cingulum, was not associated with maternal unpredictability. Addressing the overall functional significance of the uncinate and cingulum relationships, we found that the resulting imbalance of medial temporal lobe–prefrontal cortex connectivity partially mediated the association between unpredictable maternal sensory signals and impaired episodic memory function. These results suggest that unbalanced maturation of corticolimbic circuits is a mechanism by which early unpredictable sensory signals may impact cognition later in life.SIGNIFICANCE STATEMENTOur prior work across species demonstrated that unpredictable patterns of maternal care are associated with compromised memory function. However, the neurobiological mechanisms by which this occurs in humans remain unknown. Here, we identify an association of exposure to unpredictable patterns of maternal sensory signals with the integrity of corticolimbic circuits involved in emotion and cognition using state-of-the-art diffusion imaging techniques and analyses. We find that exposure to early unpredictability is associated with higher integrity of the uncinate fasciculus with no effect on a second corticolimbic pathway, the cingulum. The resulting imbalance of corticolimbic circuit development is a novel mediator of the association between unpredictable patterns of maternal care and poorer episodic memory.

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.

Objective It is widely assumed that glucocorticoids represent a primary mechanism through which exposure to adversity and maternal psychological distress shape prenatal developmental trajectories of both mother and fetus. However, despite repeated investigations and the fact that prenatal cortisol has been reliably linked to developmental outcomes, the empirical evidence supporting an association between prenatal cortisol and maternal distress is scarce. In this study, a novel approach to assessing links between maternal prenatal psychological distress and gestational cortisol profiles, general growth mixture modeling (GGMM), was applied. Method Measures of pregnancy anxiety, perceived stress, and state anxiety and depressive symptoms as well as plasma samples (for determination of cortisol) were collected from 250 women 4 times during pregnancy. Results Using GGMM, 3 cortisol trajectory groups were identified, including a typical group (n = 199) that exhibited the expected steady increase in cortisol throughout gestation, a steep group (n = 31) displaying an accelerated increase in cortisol over the course of pregnancy relative to the typical group, and a flat group (n = 20) with relatively higher cortisol levels early in pregnancy that plateaued in midgestation. Women reporting the highest distress scores exhibited trajectories expected to be associated with the least optimal developmental outcomes (flatter trajectories characterized by relatively higher levels early in gestation and lower levels late in gestation). Conclusions These findings suggest that psychological distress during pregnancy is associated with unique prenatal cortisol profiles and support further examination of this link, to enable continued evaluation of a plausible biological pathway by which maternal psychological distress programs fetal development. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Author(s): Norona-Zhou, Amanda N; Morgan, Alyssa; Glynn, Laura M; Sandman, Curt A; Baram, Tallie Z; Stern, Hal S; Davis, Elysia Poggi | Abstract: BackgroundDysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with poor physical and mental health. Early-life adversity may dysregulate cortisol response to subsequent stress. This study examines the association between patterns of maternal behavior and infant stress response to a challenge. Specifically, we test whether infant exposure to unpredictable maternal sensory signals is related to the cortisol response to a painful stressor.MethodParticipants were 102 mothers and their children enrolled in a longitudinal study. Patterns of maternal sensory signals were evaluated at 6 and 12nmonths during a 10-min mother-infant play episode. Entropy rate was calculated as a quantitative measure of the degree of unpredictability of maternal sensory signals (visual, auditory, and tactile) exhibited during the play episode. Infant saliva samples were collected for cortisol analysis before and after inoculation at 12nmonths.ResultsUnpredictable patterns of maternal sensory signals were associated with a blunted infant cortisol response to a painful stressor. This relation persisted after evaluation of covariates including maternal sensitivity and maternal psychological distress.ConclusionsThis study provides evidence that unpredictable patterns of maternal sensory signals are one process through which caregiving affects the function of infant stress response systems.

Background : The COVID-19 era is a time of unprecedented stress, and there is widespread concern regarding its short- and long-term mental health impact. Adolescence is a sensitive period for the emergence of latent psychopathology vulnerabilities, often activated by environmental stressors. The present study examined COVID-19’s impact on adolescent depression and possible influences of different domains of social connectedness (loneliness, social media use, social video game time, degree of social activity participation). Methods : A community sample of 175 adolescents (50.1% boys, mean age=16.01 years) completed questionnaires once before and twice during the COVID-19 pandemic. Piecewise growth modeling examined the acute (7 weeks) and persistent (8 months) effects of COVID-19 on depressive symptoms, and differences across sex and social connectedness. Results : Significant increases in depressive symptoms followed pandemic onset for boys and girls. However, this increase was earlier and more pronounced among girls than boys, whose depression only increased significantly during the persistent period and to a lesser degree. Trajectories of depression were influenced by loneliness and social connections. Limitations : Most participants had economic stability and minimal exposure to the virus. Exacerbation of depressive symptoms may be more severe in higher risk populations. Conclusions : Adolescent depression levels have increased during COVID-19, and are higher for girls and those who are lonely. Enhanced screening and management for adolescent depression and social connectedness could play a critical role in mitigating the negative mental health fallout of COVID-19 and future pandemics within this population.

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.

Objective Information about the adverse effects of the COVID-19 pandemic on adolescent and adult mental health is growing, yet the impacts on preschool children are only emerging. Importantly, environmental factors that augment or protect from the multidimensional and stressful influences of the pandemic on emotional development of young children are poorly understood. Methods Depressive symptoms in 169 preschool children (mean age 4.1 years) were assessed with the Preschool Feelings Checklist during a state-wide stay-at-home order in Southern California. Mothers (46% Latinx) also reported on externalizing behaviors with the Strengths & Difficulties Questionnaire. To assess the role of environmental factors in child mental health we examined household income, food insecurity, parental essential worker status and loss of parental job, as well as preservation of the structure of children's daily experiences with the Family Routines Inventory. Results Sixty-one percent of families' incomes were below the living wage and 50% had at least one parent who was an essential worker. Overall, preschoolers’ depressive and externalizing symptoms were elevated compared to pre-COVID norms. Practice of family routines robustly predicted better child mental health, and this protective effect persisted after covarying income, dual-parent status and food insecurity as well as maternal depression and stress. Conclusion The stress of the COVID-19 pandemic is exacting a significant toll on the mental health of preschool children. Importantly, maintaining a structured, predicable home environment by adherence to family routines appears to mitigate these adverse effects, providing empiric basis for public health recommendations.

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.

One of the key proposed agents of fetal programming is exposure to maternal glucocorticoids. Experimental animal studies provide evidence that prenatal exposure to elevated maternal glucocorticoids has consequences for hypothalamic-pituitary-adrenal (HPA) axis functioning in the offspring. There are very few direct tests of maternal glucocorticoids, such as cortisol, during human pregnancy and associations with infant cortisol reactivity. The current study examined the link between maternal prenatal cortisol trajectories and infant cortisol reactivity to the pain of inoculation in a sample of 152 mother-infant (47.4% girls) pairs. The results from the current study provide insight into fetal programming of the infant HPA axis, demonstrating that elevated prenatal maternal cortisol is associated with a larger infant cortisol response to challenge at both 6 and 12 months of age.

Objective: The current study examines how maternal depressive symptoms relate to child psychopathology when structured via the latent bifactor model of psychopathology, a new organizational structure of psychopathological symptoms consisting of a general common psychopathology factor (p-factor) and internalizing- and externalizing-specific risk.Method: Maternal report of depressive symptoms (Beck Depression Inventory - II) and child psychopathological symptoms (Child Behavior Checklist and Children's Behavior Questionnaire) were provided by 554 mother-child pairs. Children in the sample were 7.7years old on average (SD=1.35, range=5-11years), and were 49.8% female, 46% Latinx, and 67% White, 6% Black, 5% Asian/Pacific Islander, and 21% multiracial.Results: Maternal depressive symptoms were positively associated with the child p-factor but not with the internalizing- or externalizing-specific factors. We did not find evidence of sex/gender or race/ethnicity moderation when using latent factors of psychopathology. Consistent with past research, maternal depressive symptoms were positively associated with internalizing and externalizing composite scores on the Child Behavior Checklist.Conclusions: Findings suggest that maternal depressive symptoms are associated with transdiagnostic risk for broad child psychopathology (p-factor). Whereas the traditional Achenbach-style approach of psychopathological assessment suggests that maternal depressive symptoms are associated with both child internalizing and externalizing problems, the latent bifactor model suggests that these associations may be accounted for by risk pathways related to the p-factor rather than internalizing or externalizing specific risk. We discuss clinical and research implications of using a latent bifactor structure of psychopathology to understand how maternal depression may impact children's mental health.

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).

The etiology of autism spectrum disorder (ASD) is multifactorial, 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 study, we examined the hypothesis that fetal exposure to maternal cortisol may confer ASD risk. In addition, because ASD is four times more prevalent in males than in females, and because sexually dimorphic responses to intrauterine experiences are commonly observed, we examined 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 only among boys. 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. 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.

CONTEXT: Antenatal corticosteroids are commonly administered to pregnant women at risk for delivering between 23 and 34 gestational weeks; they provide crucial benefits to fetal lung maturation and reduce risk for neonatal morbidity and mortality. Corticosteroids are maximally efficacious for lung maturation when administered within 2 to 7 days of delivery. Accurately identifying the timing of preterm delivery is thus critical to ensure that antenatal corticosteroids are administered within a week of delivery and to avoid unnecessary administration to women who will deliver at term. A plausible biomarker for predicting time of delivery is placental corticotropin-releasing hormone (pCRH). OBJECTIVE: To assess whether pCRH concentrations predict time to delivery and specifically which women will deliver within a week of treatment. DESIGN: pCRH concentrations were evaluated before administration of the corticosteroid betamethasone, and timing of delivery was recorded. PARTICIPANTS: A total of 121 women with singleton pregnancies who were prescribed betamethasone. RESULTS: Elevated pCRH concentrations were associated with a shorter time from treatment to delivery. Receiver-operating characteristic curves revealed that pCRH may improve the precision of predicting preterm delivery. CONCLUSIONS: In the current sample, pCRH concentrations predicted the likelihood of delivering within 1 week of corticosteroid treatment. Current findings suggest that pCRH may be a diagnostic indicator of impending preterm delivery. Increasing the precision in predicting time to delivery could inform when to administer antenatal corticosteroids, thus maximizing benefits and reducing the likelihood of exposing fetuses who will be delivered at term.

Adolescence is a complex period of concurrent mental and physical development that facilitates adult functioning at multiple levels. Despite the growing number of neuroimaging studies of cognitive development in adolescence focusing on regional activation patterns, there remains a paucity of information about the functional interactions across these participating regions that are critical for cognitive functioning, including memory. The current study used structural equation modeling (SEM) to determine how interactions among brain regions critical for memory change over the course of adolescence. We obtained functional MRI in 77 individuals aged 8 to 16 years old, divided into younger (ages 8–10) and older (ages > 11) cohorts, using an incidental encoding memory task to activate hippocampus formation and associated brain networks, as well as behavioral data on memory function. SEM was performed on the imaging data for four groups (younger girls, younger boys, older girls, and older boys) that were subsequently compared using a stacked model approach. Significant differences were seen between the models for these groups. Younger boys had a predominantly posterior distribution of connections originating in primary visual regions and terminating on multi-modal processing regions. In older boys, there was a relatively greater anterior connection distribution, with increased effective connectivity within association and multi-modal processing regions. Connection patterns in younger girls were similar to those of older boys, with a generally anterior-posterior distributed network among sensory, multi-modal, and limbic regions. In contrast, connections in older girls were widely distributed but relatively weaker. Memory performance increased with age, without a significant difference between the sexes. These findings suggest a progressive reorganization among brain regions, with a commensurate increase in efficiency of cognitive functioning, from younger to older individuals in both girls and boys, providing insight into the age- and gender-specific processes at play during this critical transition period.

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.

BACKGROUND: Preterm birth remains the leading cause of neonatal morbidity and mortality, with complex biochemical pathways requiring continued understanding and assessment. OBJECTIVE: To assess the associations between maternal cortisol and placental corticotropin releasing hormone (placental CRH) concentrations with birth outcomes when stratified by placental histopathology. MATERIALS & METHODS: We conducted an analysis of 112 singleton pregnancies who received betamethasone between 23 and 34 weeks’ gestation. Maternal blood and saliva were collected prior to betamethasone administration and samples assayed for plasma cortisol (pCort), salivary cortisol (sCort), and placental CRH levels. Placental findings were characterized as inflammatory, maternal vascular underperfusion (MVU), or no pathology, and compared for the outcomes of placental CRH, pCort and sCort levels, gestational age at birth (GAB), and birthweight percentiles (BWP). RESULTS: Thirty-six subjects were characterized as inflammatory, 38 as MVU and 38 without placental abnormalities. Histopathology groups differed significantly on placental CRH levels, GAB, and BWP. Post hoc tests suggested that the MVU group had higher placental CRH than the inflammatory or no pathology groups and, despite delivering earlier than the other two groups, the inflammatory group had infants with significantly higher BWP. No differences existed between groups in terms of mean plasma or sCort levels. Higher placental CRH and pCort levels were associated with earlier GAB in the overall sample but, when split by group, these associations remained significant only among the MVU group. Higher placental CRH was also associated with lower BWP in the overall sample but did not remain significant when split by group. Higher sCort was associated with lower BWP only in the MVU group. CONCLUSION: There is differentiation of placental CRH, cortisol and birth outcomes when evaluated by placental histopathology. This highlights the importance of evaluating birth outcomes within the context of placental histopathology.

Prenatal maternal stress predicts subsequent elevations in youth depressive symptoms, but the neural processes associated with these links are unclear. This study evaluated whether prenatal maternal stress is associated with child brain development, and adolescent depressive symptoms using a prospective design with 74 mother child pairs (40 boys). Maternal stress was assessed during pregnancy, child cortical thickness at age 7, and depressive symptoms at age 12. Prenatal maternal stress was associated with less cortical thickness primarily in frontal and temporal regions and with elevated depressive symptoms; child cortical thickness additionally correlated with adolescent depressive symptoms. The observed associations are consistent with the possibility that cortical thickness in superior frontal regions links associations between prenatal maternal stress and adolescent depressive symptoms.

Glucocorticoids (cortisol in humans) are the end product of the hypothalamic-pituitary-adrenocortical (HPA) axis and are proposed as a key mechanism for programming fetal brain development. The present prospective longitudinal study evaluates the association between prenatal maternal cortisol concentrations and child neurodevelopment. Participants included a low risk sample of 91 mother-child pairs. Prenatal maternal plasma cortisol concentrations were measured at 19 and 31 gestational weeks. Brain development and cognitive functioning were assessed when children were 6–9 years of age. Structural magnetic resonance imaging scans were acquired and cortical thickness was determined. Child cognitive functioning was evaluated using standardized measures (Wechsler Intelligence Scale for Children IV and Expressive Vocabulary Test, Second Edition). Higher maternal cortisol concentrations during the third trimester were associated with greater child cortical thickness primarily in frontal regions. No significant associations were observed between prenatal maternal cortisol concentrations and child cortical thinning. Elevated third trimester maternal cortisol additionally was associated with enhanced child cognitive performance. Findings in this normative sample of typically developing children suggest that elevated maternal cortisol during late gestation exert lasting benefits for brain development and cognitive functioning 6–9 years later. The benefits of fetal exposure to higher maternal cortisol during the third trimester for child neurodevelopment are consistent with the role cortisol plays in maturation of the human fetus. It is plausible that more extreme elevations in maternal cortisol concentrations late in gestation, as well as exposure to pharmacological levels of synthetic glucocorticoids, may have neurotoxic effects on the developing fetal brain.

In many non-human species, including primates, gestational reproductive hormones play an essential role in the onset of maternal motivation and behaviors. We investigated the associations between prepartum estradiol and progesterone and maternal behavior at 1-year postpartum in 177 women. Blood was obtained at five gestational time points and an index of quality of maternal care was determined using a well-validated mother-child interaction protocol. Women who exhibited higher quality maternal care at 1-year postpartum were characterized by unique gestational profiles of estradiol, progesterone and the estrogen to progesterone ratio; specifically by slower accelerations and levels of these hormone trajectories beginning in midgestation. Further, it appeared that both fetal sex and parity moderated these findings, with first time mothers and mothers of females showing stronger associations. In sum, these data document persisting associations between prepartum hormone profiles and human maternal behavior. More broadly, these findings add to the growing literature highlighting the perinatal period as one of critical neurodevelopment in the lifespan of the human female.

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.

Perinatal depression negatively impacts mother-infant health and well-being. Previous work has linked cortisol reactivity to perinatal depressive symptoms, but moderating effects including social support and neuroticism, have not been studied. Forty-nine pregnant women (9 – 30 weeks’ gestational age; GA) provided saliva samples in response to the Trier Social Stress Test (TSST) and to awakening (cortisol awakening response, CAR), and completed questionnaires on perceived social support, personality, and depressive symptoms. Two hierarchical logistic regressions, one including the TSST response and one including the CAR as predictor variables, suggest that cortisol reactivity, social support from the baby’s father, and neuroticism contribute to depressive symptoms, controlling for GA (both p < .01). Significant statistical interactions among predictors of pregnancy depressive symptoms were, however, only found in the model using the CAR. Findings highlight the importance of considering biopsychosocial interactions in studies predicting perinatal depressive symptoms.

Objective Previous research has shown that a woman’s anxiety about her pregnancy predicts gestational length. Placental corticotrophin-releasing hormone (CRH) is a stress-responsive peptide proposed as a mechanism. We examined placental CRH as a physiological mediator of the association between pregnancy anxiety and gestational length in Latina and non-Latina White women to replicate evidence of associations between pregnancy anxiety, placental CRH and gestational length; to test whether placental CRH levels or changes mediate effects of pregnancy anxiety on gestational length; to examine ethnic differences in pregnancy anxiety, placental CRH, and gestational length; and to explore whether the effects of pregnancy anxiety on gestational length as mediated by placental CRH vary by ethnicity. Methods In a prospective study of 337 pregnant Latina and non-Latina White women, participants completed in-person interviews that included a 10-item measure of pregnancy anxiety and provided blood samples assayed using radioimmunoassay at three timepoints (19, 25, and 31 weeks gestation). Results Pregnancy anxiety at 19 and 31 weeks and levels of placental CRH at 31 weeks predicted gestational length. Tests of indirect effects were consistent with mediation such that both pregnancy anxiety at 19 weeks and increases from 19 to 31 weeks predicted placental CRH at 31 weeks, which in turn predicted gestational length. Tests of moderated mediation by ethnicity showed that the mediated effect of placental CRH at 31 weeks was significant for Latinas only. Conclusions These findings add to growing evidence of the involvement of pregnancy anxiety in the timing of birth, address mechanisms, and suggest possible ethnic differences.

Childhood exposure to traumatic events has a profound and disruptive impact on mental and physical health, including stress physiology. In the current study, we evaluate 90 pregnant women at risk for preterm delivery and assess the association between history of exposure to traumatic events and hair cortisol concentrations, an integrated measure of cortisol production. Exposure to more traumatic events in childhood and in adulthood independently predicted elevated hair cortisol concentrations in pregnancy. Notably, the impact of childhood exposure to traumatic events remained after accounting for more proximal traumatic events in adulthood. Further, there was a significant interaction between childhood and adult exposures. Traumatic experiences in adulthood were more strongly associated with hair cortisol concentrations among mothers with a history of greater childhood trauma. Findings suggest that not only do proximal adult exposures impact HPA-axis functioning during pregnancy, but that childhood traumatic experiences have persisting consequences for HPA-axis functioning during pregnancy. Maternal HPA- axis dysregulation in pregnancy has consequences for both maternal health and for fetal development. Therefore, we consider prenatal maternal HPA-axis functioning as a potential biological pathway underlying intergenerational consequences of childhood trauma.

Early life experiences influence brain function and structure throughout life. Maternal signals constitute a major source of early life experiences, and their quantity and qualities during sensitive developmental periods exert enduring effects on infant, child and adult emotional and social behaviors in humans, primates and rodents. Existing studies probing the salient qualities of maternal signals to the infant have centered primarily on measures of their valence. Here we report that in addition to these established qualitative dimensions, patterns of maternal signals contribute greatly to infants and children’s self-control, a potent predictor of mental health outcomes. In two large, independent and disparate prospective cohorts in Turku, Finland, and Irvine, CA, USA, unpredictable sequences of maternal care portended worse child self-control. Specifically, less predictable maternal signals to the infant during the first postnatal months were associated with poor self-control at the end of the first year of life. The correlation between unpredictable patterns of maternal signals and self-control persisted to school age in the cohort (Irvine) that was followed long-term. The consistency of these findings across two distinct demographic and cultural cohorts substantiates the finding that, in addition to the quality of maternal care, patterns and specifically unpredictable sequences of maternal care behaviors influence the maturation of circuits in the developing brain involved in the regulation of emotion and behavior, in a manner indicative of vulnerability to subsequent psychopathology.

Corticotropin-releasing hormone (CRH) is distributed throughout the brain and in peripheral sites but primarily is localized in the paraventricular nucleus of the hypothalamus. It is a “master” stress hormone that is responsible for the synthesis of proopiomelanocortin (POMC) in the anterior pituitary gland. Behaviorally active peptide hormones, including adrenocorticotropin hormone (ACTH) and B-endorphin, are liberated from POMC by enzymes to activate critical processes during stress. CRH is not detectable in the circulation even during extreme stress. However, during human pregnancy, the human placenta expresses the gene for CRH (pCRH) resulting in detectable levels in maternal plasma that increases 20- to 40-fold over the course of gestation. Placental CRH is identical to CRH of hypothalamic origin in size, structure, immunoreactivity, and bioactivity. However, unlike the negative feedback between adrenal cortisol and hypothalamic CRH, cortisol stimulates the synthesis and release of pCRH. The bidirectional release of pCRH into maternal and fetal compartments is associated with regulating the timing of delivery, remodeling the fetal nervous system, and influencing developmental trajectories. Fetal exposure to pCRH during early and late gestation is associated with unique patterns of cortical thinning in school-age children. Placental CRH is elevated in response to physical and behavioral stress and may be an integrative marker of early adversity.

Anhedonia, the reduced ability to experience pleasure, is a dimensional entity linked to multiple neuropsychiatric disorders, where it is associated with diminished treatment response, reduced global function, and increased suicidality. It has been suggested that anhedonia and the related disruption in reward processing may be critical precursors to development of psychiatric symptoms later in life. Here, we examine cross-species evidence supporting the hypothesis that early life experiences modulate development of reward processing, which if disrupted, result in anhedonia. Importantly, we find that anhedonia may confer risk for later neuropsychiatric disorders, especially posttraumatic stress disorder (PTSD). Whereas childhood trauma has long been associated with increased anhedonia and increased subsequent risk for trauma-related disorders in adulthood, here we focus on an additional novel, emerging direct contributor to anhedonia in rodents and humans: fragmented, chaotic environmental signals ("FRAG") during critical periods of development. In rodents, recent data suggest that adolescent anhedonia may derive from aberrant pleasure/reward circuit maturation. In humans, recent longitudinal studies support that FRAG is associated with increased anhedonia in adolescence. Both human and rodent FRAG exposure also leads to aberrant hippocampal function. Prospective studies are underway to examine if anhedonia is also a marker of PTSD risk. These preliminary cross-species studies provide a critical construct for future examination of the etiology of trauma-related symptoms in adults and for and development of prophylactic and therapeutic interventions. In addition, longitudinal studies of reward circuit development with and without FRAG will be critical to test the mechanistic hypothesis that early life FRAG modifies reward circuitry with subsequent consequences for adolescent-emergent anhedonia and contributes to risk and resilience to trauma and stress in adulthood.

Author(s): Fox, Molly; Sandman, Curt A; Davis, Elysia Poggi; Glynn, Laura M | Abstract: BACKGROUND:An issue of critical importance for psychiatry and women's health is whether postpartum depression (PPD) represents a unique condition. The Diagnostic and Statistical Manual of Mental Disorders asserts that major depressive disorder (MDD) may present with peripartum onset, without suggesting any other differences between MDD and PPD. The absence of any distinct features calls into question the nosologic validity of PPD as a diagnostic category. The present study investigates whether symptom profiles differ between PPD and depression occurring outside the postpartum phase. METHODS:In a prospective, longitudinal study of parturient women (Nn=n239), we examine the manifestation of depression symptoms. We assess factor structure of symptom profiles, and whether factors are differentially pronounced during and after the postpartum period. RESULTS:Factors were revealed representing: Worry, Emotional/Circadian/Energetic Dysregulation, Somatic/Cognitive, Appetite, Distress Display, and Anger symptoms. The factor structure was validated at postpartum and after-postpartum timepoints. Interestingly, the Worry factor, comprising anxiety and guilt, was significantly more pronounced during the postpartum timepoint, and the Emotional/Circadian/Energetic Dysregulation factor, which contained sadness and anhedonia, was significantly less pronounced during the postpartum period. CONCLUSIONS:These results suggest that PPD may be a unique syndrome, necessitating research, diagnosis, and treatment strategies distinct from those for MDD. Results indicate the possibility that Worry is an enhanced feature of PPD compared to depression outside the postpartum period, and the crucial role of sadness/anhedonia in MDD diagnosis may be less applicable to PPD diagnosis.

OBJECTIVE:The authors sought to assess associations among early-life exposure to adversity, the development and maturation of neurons and brain circuits, and neurodevelopmental outcomes. Specifically, they examined whether fetal exposure to placental corticotropin-releasing hormone (CRH), a molecule conveying maternal signals to the fetus, predicts brain growth and neuropsychiatric outcomes in school-age children. METHOD:In a large, well-characterized prospective cohort, concentrations of placental CRH (pCRH) in maternal plasma were determined during five intervals during gestation. When the children reached school age, their brain structures were examined using MRI, and emotional and cognitive tests assessing internalizing and externalizing behaviors and attention were administered (N=97, 49 of them girls). RESULTS:Levels of pCRH during gestation predicted structural and functional brain outcomes in children. Specifically, fetal exposure to elevated pCRH levels was associated with thinning of selective cortical regions and with commensurate cognitive and emotional deficits. The relations among fetal exposure to pCRH, cortical thinning, and childhood function were sex specific. CONCLUSIONS:In view of the established effects of CRH on maturation and arborization of cortical neurons, and the major contribution of dendrites to cortical volume, these findings position pCRH as an important mediator of the consequences of early-life adversity on neuropsychiatric outcomes.

It is yet unknown how similar women's hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women's reproductive life histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here, we address this important lacuna in the literature.This study aimed to investigate how consistent women's hormone profiles are across two successive pregnancies.This longitudinal, prospective study followed a cohort of 28 women across two pregnancies (PREG 1 and PREG 2). Women's circulating hormone levels were assessed from blood samples at 25, 31, and 37 weeks' gestation for adrenocorticotropic hormone (ACTH), placental corticotropin-releasing hormone (pCRH), cortisol, estradiol, and progesterone. ACTH and cortisol levels were assessed 3 months postpartum. Research questions include: Are hormone levels in PREG 2 significantly different from levels in PREG 1? What proportion of variance in PREG 2 hormone levels is attributable to variance in PREG 1 levels? Are hormone levels more stable between PREG 1 and PREG 2 compared with postpartum phases following these pregnancies? Is pCRH, which is completely placentally derived, less similar than other hormones across successive pregnancies?Pregnant women attended study visits at a university psychobiology laboratory in Southern California.Comparisons of hormone concentrations across women's successive pregnancies via paired t test revealed substantial consistency from one pregnancy to another, with only significant differences between pregnancies for pCRH. Regressions revealed substantial predictability from one pregnancy to another, with between 17-56% of PREG 2 variances accounted for by PREG 1 values. Women exhibited lower degrees of consistency and predictability in hormone levels across postpartum phases compared with gestational concentrations. This is the first study to describe maternal and placental hormone levels across successive pregnancies.

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al. open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Laceys, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.

BACKGROUND: Maternal depression is one of the most common prenatal complications. The consequences of fetal exposure to maternal depression are poorly understood. The aim of this study is to examine the association between fetal exposure to maternal depressive symptoms and cortical thickness in children 6–9 years old. METHODS: A prospective, longitudinal study of maternal depressive symptoms at 19, 25, and 31 weeks’ gestation was followed by acquisition of a structural magnetic resonance imaging scan in 81 children (age, 86.1 6 9.9 months). RESULTS: Significant (p , .01) cortical thinning in children primarily in the right frontal lobes was associated with exposure to prenatal maternal depression. The strongest association was at 25 weeks’ gestation; exposure to maternal depression at 25 gestational weeks was associated with cortical thinning in 19% of the whole cortex and 24% of the frontal lobes, primarily in the right superior, medial orbital, and frontal pole regions of the prefrontal cortex (p , .01). The significant association between prenatal maternal depression and child externalizing behavior (p , .05) was mediated by cortical thinning in prefrontal areas of the right hemisphere. CONCLUSIONS: The pattern of cortical thinning in children exposed to prenatal maternal depression is similar to patterns in depressed patients and in individuals with risk for depression. Exposure to prenatal depression coupled with subsequent cortical thinning was associated with presence of externalizing behavior in preadolescent children and may be prodromal markers of risk for dysphoria. Vulnerability to prenatal influences at 25 gestational weeks may result from the enormous growth and dramatic structural changes in the nervous system.