Decreased amygdala-sensorimotor connectivity mediates the association between prenatal stress and broad autism phenotype in young adults: Project Ice Storm.

Studies show that prenatal maternal stress (PNMS) is related to risk for child autism, and to atypical amygdala functional connectivity in the autistic child. Yet, it remains unclear whether amygdala functional connectivity mediates the association between PNMS and autistic traits, particularly in young adult offspring. We recruited women who were pregnant during, or within 3 months of, the 1998 Quebec ice storm crisis, and assessed three aspects of PNMS: objective hardship (events experienced during the ice storm), subjective distress (post-traumatic stress symptoms experienced as a result of the ice storm) and cognitive appraisal. At age 19, 32 young adults (21 females) self-reported their autistic-like traits (i.e., aloof personality, pragmatic language impairment and rigid personality), and underwent structural MRI and resting-state functional MRI scans. Seed-to-voxel analyses were conducted to map the amygdala functional connectivity network. Mediation analyses were implemented with bootstrapping of 20,000 resamplings. We found that greater maternal objective hardship was associated with weaker functional connectivity between the left amygdala and the right postcentral gyrus, which was then associated with more pragmatic language impairment. Greater maternal subjective distress was associated with weaker functional connectivity between the right amygdala and the left precentral gyrus, which was then associated with more aloof personality. Our results demonstrate that the long-lasting effect of PNMS on offspring autistic-like traits may be mediated by decreased amygdala-sensorimotor circuits. The differences between amygdala-sensory and amygdala-motor pathways mediating different aspects of PNMS on different autism phenotypes need to be studied further.

Atypical brain structure and function in young adults exposed to disaster-related prenatal maternal stress: Project Ice Storm.

Studies have shown that prenatal maternal stress (PNMS) affects brain structure and function in childhood. However, less research has examined whether PNMS effects on brain structure and function extend to young adulthood. We recruited women who were pregnant during or within 3 months following the 1998 Quebec ice storm, assessed their PNMS, and prospectively followed-up their children. T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI were obtained from 19-year-old young adults with (n = 39) and without (n = 65) prenatal exposure to the ice storm. We examined between-group differences in gray matter volume (GMV), surface area (SA), and cortical thickness (CT). We used the brain regions showing between-group GMV differences as seeds to compare between-group functional connectivity. Within the Ice Storm group, we examined (1) associations between PNMS and the atypical GMV, SA, CT, and functional connectivity, and (2) moderation by timing of exposure. Primarily, we found that, compared to Controls, the Ice Storm youth had larger GMV and higher functional connectivity of the anterior cingulate cortex, the precuneus, the left occipital pole, and the right hippocampus; they also had larger CT, but not SA, of the left occipital pole. Within the Ice Storm group, maternal subjective distress during preconception and mid-to-late pregnancy was associated with atypical left occipital pole CT. These results suggest the long-lasting impact of disaster-related PNMS on child brain structure and functional connectivity. Our study also indicates timing-specific effects of the subjective aspect of PNMS on occipital thickness.

Preconception and prenatal maternal stress are associated with broad autism phenotype in young adults: Project Ice Storm.

Studies show associations between prenatal maternal stress (PNMS) and child autism, with little attention paid to PNMS and autism in young adulthood. The broad autism phenotype (BAP), encompassing sub-clinical levels of autism, includes aloof personality, pragmatic language impairment and rigid personality. It remains unclear whether different aspects of PNMS explain variance in different BAP domains in young adult offspring. We recruited women who were pregnant during, or within 3 months of, the 1998 Quebec ice storm crisis, and assessed three aspects of their stress (i.e., objective hardship, subjective distress and cognitive appraisal). At age 19, the young adult offspring (n = 33, 22F / 11M) completed a BAP self-report. Linear and logistic regressions were implemented to examine associations between PNMS and BAP traits. Up to 21.4% of the variance in BAP total score and in BAP three domains tended to be explained by at least one aspect of maternal stress, For example, 16.8% of the variance in aloof personality tended to be explained by maternal objective hardship; 15.1% of the variance in pragmatic language impairment tended to be explained by maternal subjective distress; 20.0% of the variance in rigid personality tended to be explained by maternal objective hardship and 14.3% by maternal cognitive appraisal. Given the small sample size, the results should be interpreted with caution. In conclusion, this small prospective study suggests that different aspects of maternal stress could have differential effects on different components of BAP traits in young adults.

Urinary 1H NMR Metabolomic Analysis of Prenatal Maternal Stress Due to a Natural Disaster Reveals Metabolic Risk Factors for Non-Communicable Diseases: The QF2011 Queensland Flood Study.

Prenatal stress alters fetal programming, potentially predisposing the ensuing offspring to long-term adverse health outcomes. To gain insight into environmental influences on fetal development, this QF2011 study evaluated the urinary metabolomes of 4-year-old children (n = 89) who were exposed to the 2011 Queensland flood in utero. Proton nuclear magnetic resonance spectroscopy was used to analyze urinary metabolic fingerprints based on maternal levels of objective hardship and subjective distress resulting from the natural disaster. In both males and females, differences were observed between high and low levels of maternal objective hardship and maternal subjective distress groups. Greater prenatal stress exposure was associated with alterations in metabolites associated with protein synthesis, energy metabolism, and carbohydrate metabolism. These alterations suggest profound changes in oxidative and antioxidative pathways that may indicate a higher risk for chronic non-communicable diseases such obesity, insulin resistance, and diabetes, as well as mental illnesses, including depression and schizophrenia. Thus, prenatal stress-associated metabolic biomarkers may provide early predictors of lifetime health trajectories, and potentially serve as prognostic markers for therapeutic strategies in mitigating adverse health outcomes.

Maternal mental health mediates the effect of prenatal stress on infant temperament: The Harvey Mom Study.

Prenatal maternal stress and mental health problems are known to increase risk for developmental psychopathology in offspring, yet pathways leading to risk or resiliency are poorly understood. In a quasi-experimental design, we prospectively examined associations between disaster-related prenatal stress, maternal mental health symptoms, and infant temperament outcomes. Mothers who were pregnant during Hurricane Harvey (N = 527) reported on objective hardships (e.g., loss of belongings or income, evacuation, home flooding) related to the storm and subsequent mental health symptoms (anxiety/depression, posttraumatic stress) across time. At a postpartum assessment, mothers reported on their infant's temperament (negative affect, positive affect, orienting/regulatory capacity). Greater objective hardship indirectly predicted higher levels of infant orienting/regulatory capacity through its association with increased maternal posttraumatic stress symptoms. Greater objective hardship also indirectly predicted higher levels of infant negative affect through its association with increased maternal anxiety/depression symptoms across time. Our findings suggest a psychological mechanism linking prenatal stress with specific temperamental characteristics via maternal mental health symptoms. Findings point to the importance of high-quality assessment and mental health services for vulnerable women and young children.

Neural correlates of disaster-related prenatal maternal stress in young adults from Project Ice Storm: Focus on amygdala, hippocampus, and prefrontal cortex.

Background: Studies have shown that prenatal maternal stress alters volumes of the amygdala and hippocampus, and alters functional connectivity between the amygdala and prefrontal cortex. However, it remains unclear whether prenatal maternal stress (PNMS) affects volumes and functional connectivity of these structures at their subdivision levels. Methods: T1-weighted MRI and resting-state functional MRI were obtained from 19-year-old young adult offspring with (n = 39, 18 male) and without (n = 65, 30 male) exposure to PNMS deriving from the 1998 ice storm. Volumes of amygdala nuclei, hippocampal subfields and prefrontal subregions were computed, and seed-to-seed functional connectivity analyses were conducted. Results: Compared to controls, young adult offspring exposed to disaster-related PNMS had larger volumes of bilateral whole amygdala, driven by the lateral, basal, central, medial, cortical, accessory basal nuclei, and corticoamygdaloid transition; larger volumes of bilateral whole hippocampus, driven by the CA1, HATA, molecular layer, fissure, tail, CA3, CA4, and DG; and larger volume of the prefrontal cortex, driven by the left superior frontal. Inversely, young adult offspring exposed to disaster-related PNMS had lower functional connectivity between the whole amygdala and the prefrontal cortex (driven by bilateral frontal poles, the left superior frontal and left caudal middle frontal); and lower functional connectivity between the hippocampal tail and the prefrontal cortex (driven by the left lateral orbitofrontal). Conclusion: These results suggest the possibility that effects of disaster-related PNMS on structure and function of subdivisions of offspring amygdala, hippocampus and prefrontal cortex could persist into young adulthood.

Sharing and Safeguarding Pediatric Data.

Data sharing is key to advancing our understanding of human health and well-being. While issues related to pediatric research warrant strong ethical protections, overly protectionist policies may serve to exclude minors from data sharing initiatives. Pediatric data sharing is critical to scientific research concerning health and well-being, to say nothing of understanding human development generally. For example, large-scale pediatric longitudinal studies, such as those in the DREAM-BIG Consortium, on the influence of prenatal adversity factors on child psychopathology, will provide prevention data and generate future health benefits. Recent initiatives have formulated sound policy to help enable and foster data sharing practices for pediatric research. To help translate these policy initiatives into practice, we discuss how model consent clauses for pediatric research can help address some of the issues and challenges of pediatric data sharing, while enabling data sharing.

Elemental analysis of hair provides biomarkers of maternal hardship linked to adverse behavioural outcomes in 4-year-old children: The QF2011 Queensland Flood Study.

BACKGROUND: Exposure to adverse experiences during pregnancy, such as a natural disaster, can modify development of the child with potential long-term consequences. Elemental hair analysis may provide useful indicators of cellular homeostasis and child health. The present study investigated (1) if flood-induced prenatal maternal stress is associated with altered hair elemental profiles in 4-year-old children, and (2) if hair elemental profiles are associated with behavioural outcomes in children. METHODS: Participants were 75 children (39 boys; 36 girls) whose mothers were exposed to varying levels of stress due to a natural disaster (2011 Queensland Flood, Australia) during pregnancy. At 4 years of age, language development, attention and internalizing and externalizing problems were assessed and scalp hair was collected. Hair was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for 28 chemical elements. RESULTS: A significant curvilinear association was found between maternal objective hardship and copper levels in boys, as low and high maternal objective hardship levels were associated with the highest hair copper levels. Mediation analysis revealed that low levels of maternal objective hardship and high levels of copper were associated with lower vocabulary scores. Higher levels of maternal objective hardship were associated with higher magnesium levels, which in turn were associated with attention problems and aggression in boys. In girls, high and low maternal objective hardship levels were associated with high calcium/potassium ratios. CONCLUSION: Elemental hair analysis may provide a sensitive biomonitoring tool for early identification of health risks in vulnerable children.

Effectiveness of cognitive behavioral therapy for perinatal maternal depression, anxiety and stress: A systematic review and meta-analysis of randomized controlled trials.

Cognitive behavioral therapy (CBT) has been widely studied in prenatal or postnatal depression, with much less research on anxiety and stress. This meta-analysis aims to comprehensively evaluate CBT efficacy for perinatal depression, anxiety and stress in the short term (from baseline to immediately post-intervention) and in the long term (from baseline to the end of follow-up). Five databases were searched. We included 79 randomized controlled trials (RCTs) and quasi-RCTs assessing the efficacy of CBT during pregnancy and the first year postpartum. Primary outcome was the mean score change in depression, anxiety and stress. CBT-only and CBT plus other interventions were effective for perinatal maternal depression in the short term (SMD -0.69, 95% CI: -0.83, -0.55) and long term (SMD -0.59, 95% CI -0.75, -0.42). CBT-only had both short- and long-term efficacy for perinatal anxiety (short term: SMD -0.63, 95% CI -0.85, -0.42; long term: SMD -0.71, 95% CI -1.02, -0.39) and short-term efficacy for perinatal stress (SMD -0.96, 95% CI -1.40, -0.52). Overall, CBT was effective for perinatal maternal depression, anxiety and stress. CBT-only exhibited short-term efficacy for perinatal depression, anxiety and stress, and long-term efficacy for perinatal depression and anxiety. Subgroup analyses suggested that CBT-only was effective across a wide variety of modalities.

Effectiveness and Predictors of Outcomes in a Psychiatric Day Treatment Program for Elementary-Age.

OBJECTIVE: In this study, we aimed to (1) assess the effectiveness of an intensive multimodal day treatment program in improving externalizing problems and function in elementary-age children and (2) examine 3 predictors of the treatment outcome (i.e., family functioning, baseline severity, and comorbid disorders). METHODS: The sample included 261 children (80.9% boys) between ages of 5 and 12. A retrospective chart review, from 2013 to 2018, and a prospective chart review, from 2018 to 2019, were conducted to extract all relevant data for the present study. Parents and teachers provided reports on children's externalizing problems (i.e., aggressive behavior, attention problems, and rule-breaking behavior) and their level of function across different domains. The level of family functioning was also reported by parents, while clinicians assessed children's severity of disturbance and their diagnoses at intake. RESULTS: Based on both parents' and teachers' reports, children showed significant improvement in their externalizing problems. Moreover, children showed functional improvement at home, at school, with peers, and in hobbies by the end of the program. Based on teacher's reports, children with lower level of severity showed less improvement in their attention problems, and those with comorbid developmental problems showed less improvement in their aggressive and rule-breaking behaviors. Family functioning did not predict any treatment outcome. CONCLUSION: An intensive multimodal day treatment program was effective in reducing the symptoms of externalizing problems in elementary-age children. However, children with less severe difficulties and comorbid developmental problems showed less improvement in their externalizing problems.

Effects of maternal exposure to acute stress on birth outcomes: a quasi-experiment study.

Numerous studies have shown associations between maternal stress and poor birth outcomes, but evidence is unclear for causal inference. Natural disasters provide an opportunity to study effects of quasi-randomized hardship with an accurate measure of onset and duration. In a population-based quasi-experimental study, we examined the effect of maternal exposure to the January 1998 Québec ice storm on birth outcomes by comparing pregnant mothers who lived in an area hard hit by the ice storm with those in two unaffected regions. In a total of 147,349 singleton births between 1995 and 2001, we used a difference-in-differences method to estimate the effects of the ice storm on gestational age at delivery (GA), preterm birth (PTB), weight-for-gestational-age z-scores (BWZ), large for gestational age (LGA), and small for gestational age (SGA). After adjusting for maternal and sociodemographic characteristics, there were no differences between the exposed and the unexposed mothers for birth outcomes. The estimated differences (exposed vs. unexposed) were 0.01 SDs (95% CI: -0.02, 0.05) for BWZ; 0.10% point (95% CI: -0.95%, 1.16%) for SGA; 0.25% point (95% CI: -0.78%, 1.28%) for LGA; -0.01 week (95% CI: -0.07, 0.05) for GA; and 0.16% point (95% CI: -0.66%, 0.97%) for PTB. Neither trimester-specific nor dose-response associations were observed. Overall, exposure to the 1998 Québec ice storm as a proxy for acute maternal stress in pregnancy was not associated with poor birth outcomes. Our results suggest that acute maternal hardship may not have a substantial effect on adverse birth outcomes.

Prenatal Maternal Stress From a Natural Disaster and Hippocampal Volumes: Gene-by-Environment Interactions in Young Adolescents From Project Ice Storm.

Gene-by-environment interactions influence brain development from conception to adulthood. In particular, the prenatal period is a window of vulnerability for the interplay between environmental and genetic factors to influence brain development. Rodent and human research demonstrates that prenatal maternal stress (PNMS) alters hippocampal volumes. Although PNMS affects hippocampal size on average, similar degrees of PNMS lead to different effects in different individuals. This differential susceptibility to the effects of PNMS may be due to genetic variants. Hence, we investigated the role of genetic variants of two SNPs that are candidates to moderate the effects of PNMS on hippocampal volume: COMT (rs4680) and BDNF (rs6265). To investigate this, we assessed 53 children who were in utero during the January 1998 Quebec ice storm. In June 1998 their mothers responded to questionnaires about their objective, cognitive, and subjective levels of stress from the ice storm. When children were 11 1/2 years old, T1-weighted structural magnetic resonance imaging (MRI) scans were obtained using a 3T scanner and analyzed to determine hippocampal volumes. We collected and genotyped the children's saliva DNA. Moderation analyses were conducted to determine whether either or both of the SNPs moderate the effect of PNMS on hippocampal volumes. We found that objective hardship was associated with right hippocampal volume in girls, and that the BDNF and COMT genotypes were associated with left hippocampal volume in boys and girls. In addition, SNPs located on COMT moderated the effect of maternal objective distress in boys, and subjective distress in girls, on both right hippocampal volume. Thus, we conclude that an individual's genotype alters their susceptibility to the effects of PNMS.

Effect of Natural Disaster-Related Prenatal Maternal Stress on Child Development and Health: A Meta-Analytic Review.

The evidence supporting the idea that natural disaster-related prenatal maternal stress (PNMS) influences the child's development has been accumulating for several years. We conducted a meta-analytical review to quantify this effect on different spheres of child development: birth outcomes, cognitive, motor, physical, socio-emotional, and behavioral development. We systematically searched the literature for articles on this topic (2756 articles retrieved and 37 articles included in the systematic review), extracted the relevant data to calculate the effect sizes, and then performed a meta-analysis for each category of outcomes (30 articles included across the meta-analyses) and meta-regressions to determine the effect of some factors of interest on the association between PNMS and child development: type of PNMS (objective, psychological, cognitive, diet), type of natural disaster (ice storm, flood/cyclone), type of report (maternal, third-party observer, medical), timing of exposure (preconception exposure included or not) and child age at assessment (under 10 or 10 years and older). We found that PNMS significantly influences all spheres of child development. Higher PNMS levels were associated with longer gestational age, larger newborns, and higher BMI and adiposity levels, as well as worse cognitive, motor, socio-emotional, and behavioral outcomes.

Unexpected effects of expressive writing on post-disaster distress in the Hurricane Harvey Study: a randomized controlled trial in perinatal women.

BACKGROUND: Expressive writing requires journaling stressor-related thoughts and feelings over four daily sessions of 15 min. Thirty years of research have popularized expressive writing as a brief intervention for fostering trauma-related resilience; however, its ability to surpass placebo remains unclear. This study aimed to determine the efficacy of expressive writing for improving post-traumatic stress symptoms in perinatal women who were living in the Houston area during major flooding caused by Hurricane Harvey. METHODS: A total of 1090 women were randomly allocated (1:1:1) to expressive writing, neutral writing or no writing. Interventions were internet-based. Online questionnaires were completed before randomization and at 2 months post-intervention. The primary outcome was post-traumatic stress symptoms, measured with the Impact of Event Scale-Revised; secondary outcomes were affective symptoms, measured with the 40-item Inventory of Depression and Anxiety Scales. Feelings throughout the intervention were reported daily using tailored questionnaires. RESULTS: In intention-to-treat analyses, no post-treatment between-group differences were found on the primary and secondary outcomes. Per-protocol analyses yielded similar results. A number of putative moderators were tested, but none interacted with expressive writing. Expressive writing produced greater feelings of anxiety and sadness during the intervention compared to neutral writing; further, overall experiences from the intervention mediated associations between expressive writing and greater post-traumatic stress at 2 months post-intervention. CONCLUSIONS: Among disaster-stricken perinatal women, expressive writing was ineffective in reducing levels of post-traumatic stress, and may have exacerbated these symptoms in some.

Perinatal anxiety and depressive symptoms and perception of child behavior and temperament in early motherhood.

The perinatal period is a vulnerable time for the development of psychopathology, particularly mood and anxiety disorders. In the study of maternal anxiety, important questions remain regarding the association between maternal anxiety symptoms and subsequent child outcomes. This study examined the association between depressive and anxiety symptoms, namely social anxiety, panic, and agoraphobia disorder symptoms during the perinatal period and maternal perception of child behavior, specifically different facets of development and temperament. Participants (N = 104) were recruited during pregnancy from a community sample. Participants completed clinician-administered and self-report measures of depressive and anxiety symptoms during the third trimester of pregnancy and at 16 months postpartum; child behavior and temperament outcomes were assessed at 16 months postpartum. Child development areas included gross and fine motor skills, language and problem-solving abilities, and personal/social skills. Child temperament domains included surgency, negative affectivity, and effortful control. Hierarchical multiple regression analyses demonstrated that elevated prenatal social anxiety symptoms significantly predicted more negative maternal report of child behavior across most measured domains. Elevated prenatal social anxiety and panic symptoms predicted more negative maternal report of child effortful control. Depressive and agoraphobia symptoms were not significant predictors of child outcomes. Elevated anxiety symptoms appear to have a distinct association with maternal report of child development and temperament. Considering the relative influence of anxiety symptoms, particularly social anxiety, on maternal report of child behavior and temperament can help to identify potential difficulties early on in mother-child interactions as well as inform interventions for women and their families.

Positive cognitive appraisal "buffers" the long-term effect of peritraumatic distress on maternal anxiety: The Queensland Flood Study.

BACKGROUND: Limited research has evaluated distinct aspects of disaster experience as predictors of affective symptoms. In this study, we examined the extent to which maternal depression and anxiety over time were predicted by (1) objective hardship from a flood during pregnancy, (2) peritraumatic distress and (3) cognitive appraisal of the flood's consequences. METHODS: Data were drawn from the 2011 Queensland Flood Study, a prospective, longitudinal study of pregnancy (n = 183). Mothers' disaster experience was measured within 1 year after the flood. Their levels of depression, anxiety and stress were measured at 16 months, 30 months, 4 years and 6 years after childbirth. Linear mixed models were employed to evaluate symptom trajectories. RESULTS: There were no time-dependent effects of disaster-related variables. Objective hardship did not predict outcomes. Peritraumatic distress significantly predicted depression and anxiety symptoms when cognitive appraisal was negative. Conversely, when cognitive appraisal was neutral or positive, the effect of peritraumatic distress was "buffered". For anxiety, but not depression, this interaction survived Bonferroni correction. Neutral/positive cognitive appraisal similarly moderated the effect of peritraumatic dissociation. LIMITATIONS: The generalizability of our findings is limited by overall low levels of depression and anxiety, along with a predominantly Caucasian, higher socioeconomic status sample. Potential confounders such as pre-disaster anxiety were not controlled for. CONCLUSION: In line with previous evidence, this study supports the predictive validity of peritraumatic distress for post-disaster depression and anxiety. Our findings suggest that cognitive appraisal could be a relevant target for interventions aimed at fostering maternal resilience.

Measuring resilience in children: a review of recent literature and recommendations for future research.

PURPOSE OF REVIEW: Understanding variability in developmental outcomes following exposure to early life adversity (ELA) has been an area of increasing interest in psychiatry, as resilient outcomes are just as prevalent as negative ones. However, resilient individuals are understudied in most cohorts and even when studied, resilience is typically defined as an absence of psychopathology. This review examines current approaches to resilience and proposes more comprehensive and objective ways of defining resilience. RECENT FINDINGS: Of the 36 studies reviewed, the most commonly used measure was the Strengths and Difficulties Questionnaire (n = 6), followed by the Child Behavior Checklist (n = 5), the Resilience Scale for Chinese Adolescents (n = 5), the Rosenberg Self-Esteem Scale (n = 4), and the Child and Youth Resilience Scale (n = 3). SUMMARY: This review reveals that studies tend to rely on self-report methods to capture resilience which poses some challenges. We propose a complementary measure of child resilience that relies on more proactive behavioral and observational indicators; some of our preliminary findings are presented. Additionally, concerns about the way ELA is characterized as well as the influence of genetics on resilient outcomes prompts further considerations about how to proceed with resiliency research.

Disaster-related prenatal maternal stress, and childhood HPA-axis regulation and anxiety: The QF2011 Queensland Flood Study.

BACKGROUND: The fetal programming hypothesis suggests that prenatal maternal stress (PNMS) influences aspects of fetal development, such as the Hypothalamic Pituitary Adrenal (HPA) axis, enhancing susceptibility to emotional problems. No study (to our knowledge) has investigated this pathway considering development of preschool anxiety symptoms. Using data from the Queensland Flood study (QF2011), our objective was to determine whether toddler HPA-axis functioning mediated the association between aspects of flood-related PNMS and child anxiety symptoms at 4-years, and whether relationships were moderated by the timing of the stressor in utero or by the child's sex. METHODS: Women, pregnant during the 2011 Queensland floods (N = 230), were recruited soon afterwards and completed questionnaires regarding their objective hardship (e.g., loss of personal property), subjective distress (post-traumatic-like symptoms) and cognitive appraisal of the disaster. At 16 months, indexes of the child's diurnal cortisol rhythm (awakening response, total daily output, diurnal slope [N = 80]), and stress reactivity (N = 111), were obtained. At 4-years, N = 117 mothers reported on their own mood and their children's anxiety symptoms; of these, N = 80 also had valid child cortisol reactivity data, and N = 64 had diurnal cortisol rhythm data. RESULTS: A greater cortisol awakening response at 16 months mediated the relationship between subjective PNMS and anxiety symptoms at 4-years. Greater toddler daily cortisol secretion predicted more anxiety symptoms, independent of PNMS. The laboratory stressor did not elicit a cortisol response. PNMS effects were not dependent upon child sex nor on gestational timing of flood exposure. CONCLUSIONS: Indexes of diurnal cortisol in toddlerhood may represent vulnerability for anxiety symptoms in preschoolers, both independent of, and following, exposure to disaster-related prenatal maternal subjective distress.

Disaster-related prenatal maternal stress predicts HPA reactivity and psychopathology in adolescent offspring: Project Ice Storm.

BACKGROUND: Prenatal stress has been associated with adverse outcomes in offspring, including elevated risk of psychopathology. Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been posited as a biological mechanism underlying such consequences. The present study aimed to examine whether dysregulation of the offspring HPA axis mediates the relationship between prenatal stress exposure and adolescent psychopathology. METHODS: Five months after the Quebec ice storm of 1998, women who had been pregnant at the time of the storm completed questionnaires about their objective hardship and subjective distress from the disaster. A total of 45 of their children, exposed to the ice storm in utero, participated at 13 years of age. Adolescents completed the Trier Social Stress Test while providing salivary samples to measure circulating cortisol levels. Maternal report of adolescent behaviors was assessed with the Child Behavior Checklist. RESULTS: Results from the study found that greater objective hardship was associated with elevated offspring cortisol reactivity at 13 years of age. Furthermore, greater subjective distress was associated with greater externalizing behaviors. While lower cortisol reactivity predicted greater externalizing behaviors, it did not mediate the association between maternal objective hardship or subjective distress and offspring externalizing or internalizing behaviors. CONCLUSIONS: Findings suggest that objective hardship in pregnancy has long-term implications for offspring HPA axis functioning, which is also associated with externalizing behaviors. While dysregulation of the offspring HPA axis did not mediate the association between prenatal stress and offspring psychopathological symptoms, further research is warranted to investigate programming of alternative biological systems.

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm.

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys. Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS. Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors. Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors. Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience.