Literature Review

Annual Research Review: Prenatal stress and the origins of psychopathology: an evolutionary perspective

Article· Literature ReviewinJournal of Child Psychology and Psychiatry 52(4):356-67 · April 2011with 1,406 Reads 
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Abstract
If a mother is stressed or anxious while pregnant her child is more likely to show a range of symptoms such as those of attention deficit hyperactivity disorder, conduct disorder, aggression or anxiety. While there remains some debate about what proportion of these effects are due to the prenatal or the postnatal environment, and the role of genetics, there is good evidence that prenatal stress exposure can increase the risk for later psychopathology. Why should this be? In our evolutionary history it is possible that some increase in these characteristics in some individuals was adaptive in a stressful environment, and that this type of fetal programming prepared the child or group for the environment in which they were going to find themselves. Anxiety may have been associated with increased vigilance, distractible attention with more perception of danger, impulsivity with more exploration, conduct disorder with a willingness to break rules, and aggression with the ability to fight intruders or predators. This adaptation for a future dangerous environment may explain why stress and anxiety, rather than depression, seem to have these programming effects; why there is a dose-response relationship with prenatal stress from moderate to severe and it is not only toxic stress that has consequences; why not all children are affected and why individual children are affected in different ways; and why the outcomes affected can depend on the sex of the offspring. An evolutionary perspective may give a different understanding of children in our society with these symptoms, and suggest new directions for research. For example, there is some evidence that the type of cognitive deficits observed after prenatal stress have specific characteristics; these may be those which were adaptive in a past environment.

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  • ... Cette prévalence est doublée ou triplée parmi les femmes présentant des facteurs de vulnérabilité sociale [11]. Le mal-être psychologique des femmes enceintes ou les facteurs de vulnérabilité sociale tels qu'un faible niveau d'étude, l'absence d'emploi, une nationalité étrangère sont fortement associés à un moins bon suivi de la grossesse, une fréquence accrue de pathologies médicales en cours de grossesse et une morbidité néonatale accrue [11][12][13]. Après la naissance, ils sont associés à des troubles émotionnels chez les parents, des troubles relationnels entre les parents et l'enfant et des troubles de développement cognitifs et émotionnels chez l'enfant [13][14][15]. ...
    Article
    Full-text available
    Près de 10 % des femmes enceintes françaises déclarent avoir ressenti un mal-être psychologique au cours de leur grossesse. Cette prévalence peut être doublée ou triplée parmi les femmes présentant des facteurs de vulnérabilité sociale. Parmi ces femmes, 81,3 % n’ont pas consulté un professionnel de santé au cours de leur grossesse pour ces difficultés. Le projet Bien-être vise à améliorer le repérage précoce des vulnérabilités psychologiques ou sociales et le parcours de soin actuel des femmes enceintes vulnérables, et à évaluer l’intérêt de l’entretien prénatal précoce dans l’accompagnement de ces femmes.
  • ... As previous studies found that mothers tend to describe child behavior, the mother-infant relationship and child temperament according to their current mood, a critical range of possible bias in maternal evaluation can be assumed, especially in mothers with symptoms of depression or anxiety (Atella, DiPietro, Smith, & James-Roberts, 2003;Pauli-Pott, Ries-Hahn, Kupfer, & Beckmann, 1999). Contrary to the vast amount of findings reporting an impairing influence of prenatal stress on the infant, as well as research on mother-infant behavior (Angelidou et al., 2012;Gardener et al., 2009;Glover, 2011;Juruena, 2014), the present results showed higher psychosocial PS to be related to more positive mother-infant dyadic behavior. For example, de Weerth and colleagues (2003) reported that more negative facial expressions, crying, and fussing in 5-month-old infants during routine mother-child interaction were related to higher prenatal maternal cortisol levels at the end of pregnancy. ...
    Thesis
    Early life stress is known to influence mothers and consequently also the infant pre-, peri-, and postnatally. Both stress sensitization and inoculation theories have speculated about the conflicting previous findings of beneficial as well as impairing influences of early life stress. Findings of an impact on infant development, behavior and later vulnerability for cognitive and emotional problems, physical diseases and mental disorders, suggested the need to identify possible pathways between early life stress and infant outcome. Suggested underlying processes, such as fetal programming, were discussed. The present thesis focused on the possible impact of prenatal maternal stress on mother-infant dyadic behavior in a standardized observation paradigm, i.e. the still-face paradigm. Study I aimed to illuminate the prospective influence of psychological and physiological stress during pregnancy on mother-infant dyadic behavior in the first play episode of the still-face paradigm. In Study II, both the first play episode and the reunion episode were investigated. In Study I, the first play episode of the still-face paradigm was investigated. The findings provided evidence of an impact of psychosocial prenatal stress on mother-infant dyadic behavior during the normal mother-infant play, as it was expected for the first play episode. Mother-infant dyads with more psychosocial PS in pregnancy showed significantly more positive dyadic behavior then the less stressed dyads. The same was found for perceived maternal prenatal stress, although the effect vanished when analyses were conducted including all covariates. Hence, the findings were considered as providing only restricted evidence. No other stress index (i.e., psychopathological PS, cortisol decline and cortisol AuCg) reached significance in predicting mother-infant dyadic play behavior. In Study II, the impact of prenatal stress on mother-infant dyadic behavior in both play situations of the still-face paradigm was investigated. The dyadic behavior in the first play episode was compared with that in the reunion episode. The results provided evidence for the “still-face” and “carry-over” effect, with mother-infant dyads in both the high- and low-stress groups showing decreasing positive and increasing negative dyadic behavior in the reunion episode. Here too, mother-infant dyads with higher psychosocial prenatal stress showed significantly more positive dyadic behavior in the first play episode, but not in the reunion episode. In the latter episode, the positive behavior of the dyads with high prenatal stress decreased to approximately the same level as that of the dyads with low stress. In Study II, significant results emerged for physiological stress dimensions, with mother-infant dyads with a prenatally flat diurnal cortisol decline and low diurnal cortisol AUCg levels showing a distinctive, significant increase in negative dyadic behavior in the reunion episode. Mediation analyses run in both studies showed that maternal behavior was not a significant mediator between prenatal stress and infant behavior. The present findings contribute to inoculation theories on the impact of stress. Nevertheless, both studies provide merely a glimpse into the complex relationship of early life stress factors, maternal and environmental factors, and the infant’s development. Taken together, given the vast amount of studies reporting an impairing impact of prenatal stress on the infant, the present results should be interpreted with caution. The results add further support to the idea of individual resilience factors, suggesting that some individuals are not influenced by stressors or even benefit from them. Future research should focus on the underlying mechanisms, such as early programming, sensitive time periods in infant development, as well as possible influencing factors, in order to contribute to the explaining the mixed results, and to inform the creation of preventive programs for mothers and infants.
  • ... Although an array of prenatal environmental influences have been associated with conduct problems in children (e.g., obstetric complications, prenatal stress and internalizing problems, Gaysina et al., 2013;Glover, 2011;Lukkari et al., 2012;O'Connor, Heron, Golding, Beveridge, & Glover, 2002), the strongest evidence for the role of prenatal risk on children's conduct problems is maternal substance use during pregnancy. For example, exposure to maternal smoking during pregnancy (SDP) has been associated with an increased risk of conduct problems from childhood into adulthood (Langley, Holmans, van den Bree, & Thapar, 2007;Nigg & Breslau, 2007;Wakschlag & Hans, 2002;Wakschlag, Pickett, Cook, Benowitz, & Leventhal, 2002). ...
    Article
    This study examines interactions of heritable influences, prenatal substance use, and postnatal parental warmth and hostility on the development of conduct problems in middle childhood for boys and girls. Participants are 561 linked families, collected in 2 cohorts, including birth parents, adoptive parents, and adopted children. Heritable influences on internalizing and externalizing (including substance use) problems were derived from birth mothers' and fathers' symptoms, diagnoses, and age of onset from diagnostic interviews, and the proportion of first-degree relatives with the same type of problems. Smoking during pregnancy (SDP) and alcohol use during pregnancy were assessed retrospectively from birth mothers at 5 months postpartum. Earlier externalizing problems and parental warmth and hostility and were assessed at 1 assessment prior to the outcome (Cohort II: 4.5 years; Cohort I: 7 years). Conduct problems were symptoms from a diagnostic interview assessed at age 6 (Cohort II) or 8 (Cohort I). Findings from regression analyses suggest that (a) SDP plays an important role for the development of conduct problems, (b) some relatively well-accepted effects (e.g., parental hostility) were less important when simultaneously considering multiple factors influencing the development of conduct problems, and (c) main effects of genetic risk and SDP, and interactions among genetic risk and postnatal warmth, SDP and postnatal warmth, and genetic risk, SDP, and postnatal hostility for conduct problems were important for boys' but not girls' conduct problems. Replication is needed, but the current results provide preliminary but empirically grounded hypotheses for future research testing complex developmental models of conduct problems. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
  • ... We argue that these women also represent a particularly vulnerable subgroup that is critical to identify and offer comprehensive followup. Also, a persistent high level of concern can generate excessive negative stress for both mother and foetus (Glover 2011). ...
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    Background Women with bipolar disorder have a high risk of illness relapse postpartum, including psychosis. The aim of the study was to explore how perinatal women with bipolar disorder relate to the risk. What are their concerns? How do they prepare for the dual demands of mood episodes and motherhood? Methods A qualitative study was conducted. To ensure rich insight into the research questions, 13 primiparous and 13 multiparous women with bipolar disorder (I or II), were individually interviewed in pregnancy or early postpartum. Thematic analysis was applied. Results Across parity, concerns for illness relapse included concerns for depression and psychosis. Primiparous women worried about “the unknown” in relation to postpartum reactions. Overall, the most significant concerns were the impact of mood episodes on mothering and on the partner. Concerns regarding the infant were maternal medication, mood episodes affecting the child, and heredity. Resources and preparations included: support from the partner, the family, and health services; adjustment of daily life; and mental strategies. Women were aware of the postpartum risk, but their levels of personal concern varied between low, moderate and high. Women with low level of concern for illness relapse had made the least deliberations and preparations. A subgroup of women with high level of concern also had limited resources and preparations. Conclusions The findings highlight the importance of including a psychological and psychosocial focus in perinatal prevention planning and counselling. Even if women with BD are informed about the increased risk of illness relapse postpartum, they relate to it differently. Their level of personal concern impacts their perinatal deliberations and preparations, which in turn may impact postpartum adjustment. When counselling these women, it is important to assess their personal risk recognition, perinatal concerns and available resources and preparations, and support them accordingly. Extra attention should be given to women with a low level of concern, and women with a high level of concern who have limited resources and preparations. These women represent particularly vulnerable subgroups that are critical to identify and offer comprehensive follow-up.
  • ... Additionally, maternal glucocorticoid exposure had potential impacts on reproductive dysfunction in male offspring. For example, prenatal stress exposure induced low levels of serum testosterone, delayed puberty establishment, and caused abnormal sexual behaviors [37,38]. Glucocorticoids act by binding to intracellular GR [39]. ...
    Article
    Prenatal ethanol exposure (PEE) could affect offspring’s testicular development. This study aimed to illuminate its intrauterine origin and the programming mechanism caused by PEE. Pregnant Wistar rats were given ethanol (4 g/kg.d) by gavage administration during gestational days (GD) 9–20. Serum samples and testes of male offspring rats were collected on GD20, postnatal week (PW) 6, and PW12. We found that PEE induced testicular morphological abnormality, low serum testosterone levels, expressive suppression of 3β-hydroxysteroid dehydrogenase (3β-HSD), and low acetylation levels of histone 3 lysine 14 (H3K14ac) of 3β-HSD before and after birth. In utero, when fetal rats were overexposed to corticosterone by PEE, the expression levels of testicular glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) were increased, while that of steroidogenic factor 1 (SF1) was decreased. In vitro, corticosterone (rather than ethanol) at 500 to 2,000 nM concentration decreased testosterone production and 3β-HSD expression in a concentration-dependent manner. Moreover, corticosterone downregulated SF1 and upregulated HDAC2 via activating GR, accompanied by a low H3K14ac level of 3β-HSD; SF1 overexpression could reverse the increased HDAC2 expression, and knockdown of HDAC2 could partially reverse the inhibitory effects of corticosterone on H3K14ac level and 3β-HSD expression but not on SF1 expression. Taken together, PEE caused testicular dysplasia in male offspring rats, which was associated with corticosterone-induced low-functional programming of 3β-HSD through the GR/SF1/HDAC2/H3K14ac pathway. This study provides new academic perspectives to illuminate the theory of ‘Developmental Origins of Health and Disease.’
  • ... In what follows, we consider the prenatal developmental origins of risk for future psychopathology as a potential consequence of exposure to maternal affect dysregulation. Some DOHaD studies demonstrate associations between prenatal environmental exposure to household chemicals and child neurodevelopmental outcomes (Lam et al. 2017), while others assert that one form of maternal distress has more of an impact on the developing child (Glover 2011). We focus on research relevant to the idea that there is a third pathway for the familial inheritance of risk for psychiatric illness beyond shared genes and the quality of parental care: the impact of pregnant women's distress-defined broadly to include perceived stress, life events, depression, and anxiety-on fetal and infant brain-behavior development. ...
    Article
    The developmental origins of health and disease hypothesis applied to neurodevelopmental outcomes asserts that the fetal origins of future development are relevant to mental health. There is a third pathway for the familial inheritance of risk for psychiatric illness beyond shared genes and the quality of parental care: the impact of pregnant women's distress—defined broadly to include perceived stress, life events, depression, and anxiety—on fetal and infant brain–behavior development. We discuss epidemiological and observational clinical data demonstrating that maternal distress is associated with children's increased risk for psychopathology: For example, high maternal anxiety is associated with a twofold increase in the risk of probable mental disorder in children. We review several biological systems hypothesized to be mechanisms by which maternal distress affects fetal and child brain and behavior development, as well as the clinical implications of studies of the developmental origins of health and disease that focus on maternal distress. Development and parenting begin before birth. Expected final online publication date for the Annual Review of Clinical Psychology Volume 15 is May 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
  • ... Lo que ocurra durante las 40 semanas de gestación va a condicionar en gran medida el desarrollo infantil. Diversas investigaciones han revelado que la salud psicológica materna influye en el desarrollo fetal y que esto tiene repercusiones a lo largo del desarrollo del niño al asociarse con diferentes psicopatologías de inicio en la infancia, como los trastornos de conducta y los trastornos de aprendizaje (Glover, 2011;Li, Olsen, Vestergaard y Obel, 2010). ...
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    Full-text available
    Babies exposed to high levels of maternal anxiety during the prenatal period may develop a more reactive HPA (hypothalamic-pituitary-adrenal) axis, which poses a vulnerability to psychopathology. In this prospective study, we investigated the relationships between antenatal maternal anxiety, infant psychological developmen,t and HPA axis reactivity in 2 to 3-month-old babies. We use data from forty-six mother-child dyads. The main analysis did not reveal significant relationships between the variables studied, but the variability pointed out that antenatal maternal anxiety could be associated with differential effects on the reactivity of the HPA axis according to the child’s psychological development. In addition, the results indicated that mothers with prenatal anxiety presented other psychopathological symptoms, such as interpersonal sensitivity (p < .001) and obsession-compulsion (p < .001). This is significant for future research and - at a clinical level - to promote psychological interventions during pregnancy.
  • ... A saúde mental da gestante é fator de risco para ansiedade e depressão pós-natal 6,7 . Para a criança, o transtorno materno aumenta o risco de ansiedade, depressão, transtorno de atenção, hiperatividade e déficits cognitivos na vida extrauterina [8][9][10][11][12][13][14][15] . Pode ainda resultar em recém-nascidos pequenos para a idade gestacional 16 devido ao excesso de cortisol liberado pela gestante 17 , anormalidades em diversos tecidos fetais e prematuridade, além de provavelmente estar ligado à baixa resposta do sistema imune adaptativo fetal às vacinas, o que explicaria o aumento das taxas de doenças infecciosas e autoimunes [17][18][19] . ...
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    Objective: To perform a cross-cultural adaptation of the Prenatal Diagnostic Procedures Anxiety Scale questionnaire for application in the Brazilian cultural context. Methods: The translation and back translation processes followed internationally accepted criteria. A committee of experts evaluated the semantic, idiomatic, experimental and conceptual equivalence, proposing a pre-final version that was applied in 10.0% of the final sample. Afterwards, the final version was approved for the psychometric analysis. At that stage, 55 pregnant women participated which responded to the proposed Brazilian version before taking an ultrasound examination at a public hospital in Santa Catarina, in the year of 2017. The Edinburgh Postnatal Depression Scale was used as an external reliability parameter. The internal consistency of the instrument was obtained by Cronbach's alpha. Validation was performed by exploratory factorial analysis with extraction of principal components by the Kaiser-Guttman method and Varimax rotation. Results: The Cronbach's alpha value of the total instrument was 0.886, and only the percentage of variance from item 2 (0.183) was not significant. The Kaiser-Guttman criterion defined three factors responsible for explaining 78.5% of the variance, as well as the Scree plot. Extraction of the main components by the Varimax method presented values from 0.713 to 0.926, with only item 2 being allocated in the third component. Conclusions: The Brazilian version is reliable and valid for use in the diagnosis of anxiety related to the performance of ultrasound procedures in prenatal care. Due to the lack of correlation with the rest of the construct, it is suggested that item 2 be removed from the final version.
  • ... For example, PND has been associated with insecure attachment patterns in infants (Murray, 1992) , lower intelligence quotient scores in children (Hay et al., 2001) and a risk for the later development of affective disorders in adolescents (Halligan et al., 2007). Antenatal anxiety has additionally been associated with disrupted emotional regulation and later psychopathology in exposed offspring (Beydoun et al., 2008;Glover, 2011;Sandman et al., 2012). Some of the risk factors associated with PND, such as lower socioeconomic status and familial interpersonal stress, could also negatively impact child development (Barker et al., 2012;Murray, 1992). ...
    Article
    Full-text available
    Depression is the most common perinatal psychiatric disorder, but little is known about how it may impact offspring neurodevelopment, as well as the mechanisms by which it may confer transgenerational psychiatric risk. This review presents imaging studies conducted to evaluate the relationship between perinatal depression (PND) and infant and child neurodevelopment. Altered structural and functional connectivity is implicated in children exposed to PND and anxiety. Overall, there are changes in connectivity between amygdala and the prefrontal cortex. Studies suggest decreased hippocampal growth in the first 6 months after birth, decreased cortical thickness in children, and increased amygdala volumes, that are more pronounced in female offspring. Future research is needed to understand the impact of PND on development so that early interventions which promote mother–infant bonding and cognitive development may improve developmental outcomes in children exposed to PND, reducing later risk of psychopathology.
  • ... A wealth of research indicates that prenatal stress predicts a number of altered and often deleterious child outcomes (for review, see Entringer, Buss, & Wadhwa, 2015;Glover, 2014;Tarabulsy et al., 2014; Van den Bergh, Mulder, Mennes, & Glover, 2005), including preterm birth and low birth weight ( Wadhwa et al., 2002), deficiencies in intellectual and language functioning ( Laplante et al., 2004), ADHD symptoms ( Grossman et al., 2003), externalizing and anxiety problems (Glover, 2011), and motor and mental developmental disorders (Kofman, 2002;Tarabulsy et al., 2014). Although such human evidence suggests that prenatal stress disrupts "optimal" development, we present evidence for a different view on how and why prenatal stress has been repeat- edly associated with impaired functioning. ...
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    Full-text available
    Separate fields of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are themselves associated with increased susceptibility to both positive and negative environmental influences. Collectively, this work supports Pluess and Belsky's (Psychopathology, 2011, 23, 29) claim that prenatal stress fosters, promotes or “programs” postnatal developmental plasticity. Herein, we review animal and human evidence consistent with this hypothesis before advancing the novel idea that infant intestinal microbiota may be one candidate mechanism for instantiating developmental plasticity as a result of prenatal stress. We then review research indicating that prenatal stress predicts differences in infant intestinal microbiota; that infant intestinal microbiota is associated with behavioral and physiological reactivity phenotypes; and, thus, that prenatal stress may influence infant intestinal microbiota in a way that results in heightened physiological and behavioral reactivity and, thereby, postnatal developmental plasticity. Finally, we offer ideas for testing this claim and consider implications for intervention and use of probiotics during early infancy.
  • ... The present observations corroborate the idea that adverse early life experiences, such as prenatal stress, are major determinants of brain development and mental health. Human studies have demonstrated that children exposed to prenatal stress are more vulnerable to emotional disturbances in adolescence and adulthood than non-exposed children 28 . Similarly, rodent studies revealed that exposure to prenatal or chronic postnatal stress raises levels of anxiety-like behaviours, such as spending less time than controls in the open arms of the EPM 29 and enhanced freezing 30 . ...
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    Experiences during early development are powerful determinants of lifetime mental health. Here we investigated if ancestral stress regulates the brain’s epigenetic memory to alter neuromorphology and emotionality in the remote F4 progeny. Pregnant female rat dams of the parental F0 generation were exposed to stress on gestational days 12–18. To generate a transgenerational stress lineage, their pregnant daughters (F1), grand-daughters (F2) and great-grand-daughters (F3) remained undisturbed. To generate a multigenerational stress lineage, pregnant dams of each generation (F1–F3) were stressed. A lineage of non-stress controls (F0–F3) was also produced. Multigenerational stress exceeded the impact of transgenerational stress by increasing anxiety-like behaviours and stress response in young and middle-aged F4 males but not females. Functional changes were accompanied by reduced spine density in the male medial prefrontal cortex with opposite effects in the orbital frontal cortex. Ancestral stress regulated cortical miR-221 and miR-26 expression and their target genes, thus downregulating ntrk2 and map1a genes in males while downregulating crh and upregulating map1a genes in females. These miRNA-dependent pathways are candidates for developmental programming of lifetime mental health. Thus, multigenerational stress in particular determines sexually dimorphic predisposition to stress vulnerability and generates a phenotype resembling symptoms of post-traumatic stress disorder.
  • ... Psychosocial factors may also have a role beyond purely modifying outcomes. For instance, it is now established in human and animal models that intense maternal stress during pregnancy may have long-term biological and behavioral effects on the child [219][220][221]. In addition, extreme deprivation in infancy such as that experienced in institutions with impoverished levels of care, stimulation, and attention may have adverse effects on developmental psychopathology and physical development [222]. ...
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    Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc–copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene–environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.
  • ... Instead, the effects of paternal psychiatric symptoms on the child may either be mediated by the mother experiencing higher psychosocial distress due to the father's psychological distress [40,41] or by potential epigenetic effects of in paternal sperm, resulting in DNA methylation in the offspring [44,45]. Moreover, direct genetic effects are among the potential mechanisms to explain the effects of prenatal distress on child outcomes, for both parents, as child characteristics and prenatal distress experienced by the parents may indicate a shared underlying genotype [46,47]. Overall, very few studies focus on paternal and maternal prenatal psychiatric symptoms simultaneously within the same study. ...
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    Maternal prenatal symptoms of depression and anxiety have been suggested to impose differential effects on later offspring development, depending on their characteristics, such as timing, intensity and persistence. Paternal symptoms have been less investigated. While knowledge on these trajectory characteristics is essential for improved comprehension of prenatal stress, prospective studies including both expecting parents have been scarce. We aim at identifying and comparing the trajectories of prenatal depressive and anxiety symptoms in both parents in a pregnancy cohort design. The sample included 3202 mothers and 2076 fathers who were recruited to the FinnBrain Birth Cohort study (www.finnbrain.fi). Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) and general anxiety by the anxiety scale of the Symptom Checklist -90 (SCL-90) repeatedly at 14, 24, and 34 gestational weeks. Five differential depressive and four anxiety symptom trajectories were identified across pregnancy both in mothers and in fathers. The trajectories of consistently low depressive or anxiety symptoms were associated with higher educational level in both parents, and with nulliparity and non-smoking during pregnancy in mothers. Parents with consistently high or increasing levels of symptoms had more often prenatal SSRI medication. The congruences between elevated depressive and anxiety symptoms at any point in pregnancy, as well as parental trajectories within families were low. However, in this population-based sample, the self-reported symptom levels of both parents were generally very low. Variance in timing and persistence of parent-reported prenatal depressive and anxiety symptoms is potentially important, while symptom trajectories are very similar in mothers and fathers. These differential symptom trajectories and the significance of their correlates should be acknowledged when studying prenatal stress exposures and the related outcomes in children.
  • ... One of the most central alternative route for above-mentioned mechanisms of programming is suggested to be through genetic inheritance. First, both the child characteristics and prenatal stress experienced by the mother might share the same underlying genotype (Glover, 2011;O'Donnell & Meaney, 2017). Second, offspring susceptibility to stress exposure is shown to be moderated by the genotype of the offspring (Babineau et al., 2015;Velders et al., 2012;Zohsel et al., 2014), although these findings have been inconsistent (Braithwaite et al., 2013). ...
  • ... Parental stress has been associated with offspring's greater risk of psychopathology (Glover, 2011), higher glucocorticoid sensitivity (Lehrner et al., 2014), immunological alterations (Laviola et al., 2004), enhanced neuronal activity (Bielas et al., 2014) and altered DNA methylation (Mulligan et al., 2012;Essex et al., 2013). Recently, epigenetic inheritance is assigned a captivating role in the intergenerational outcomes , stressing the standing of "epigenetics prior to the birth" (Lo and Zhou, 2014). ...
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    While the positive effects of environmental enrichment (EE) applied after weaning, in adulthood, during aging, or even in the presence of brain damage have been widely described, the transgenerational effects of pre-reproductive EE have been less examined. And yet, this issue is remarkable given that parental environmental experience may imprint offspring’s phenotype over generations through many epigenetic processes. Interactions between individual and environment take place lifelong even before conception. In fact, the environment pre-reproductively experienced by the mother and/or the father exerts a substantial impact on neural development and motor and cognitive performances of the offspring, even if not directly exposed to social, cognitive, physical and/or motor enrichment. Furthermore, pre-reproductive parental enrichment exerts a transgenerational impact on coping response to stress as well as on the social behavior of the offspring. Among the effects of pre-reproductive parental EE, a potentiation of the maternal care and a decrease in global methylation levels in the frontal cortex and hippocampus of the progeny have been described. Finally, pre-reproductive EE modifies different pathways of neuromodulation in the brain of the offspring (involving brain-derived neurotrophic factor, oxytocin and glucocorticoid receptors). The present review highlights the importance of pre-reproductive parental enrichment in altering the performances not only of animals directly experiencing it, but also of their progeny, thus opening the way to new hypotheses on the inheritance mechanisms of behavioral traits.
  • ... As highlighted in this section, maternal stress during pregnancy predicts a large number of unfavorable outcomes in the offspring, in- cluding more severe behavioral problems, motor problems and poorer cognitive development, psychopathology and alterations in brain de- velopment, HPA-axis and ANS function. For many of these outcomes, there does not appear to be any evolutionary advantage, that is, there is little evidence that the consequences of maternal stress in pregnancy enhance the unborn child's chances of immediate survival or long-term health, as might be predicted from some fetal programming theories (Del Giudice, 2014;Glover, 2011;Nederhof and Schmidt, 2012). There are a handful of studies, however, that do suggest that a moderate degree of maternal stress infers slight advantages to infant and child outcomes, whether that stress is maternal psychological distress ( DiPietro et al., 2010;DiPietro et al., 2006;Kantonen et al., 2015;Lin et al., 2014;Rothenberger et al., 2011b) or maternal objective exposure from a natural disaster ( Laplante et al., 2008;Simcock et al., 2016a). ...
    Article
    Depression is a common condition affecting up to 20% of all pregnant women, and is associated with subsequent developmental and behavioral problems in children, such as conduct disorder and ADHD. One proposed mechanism underlying these associations is modification of the fetal hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system (ANS), resulting in altered responses to stress. This review examined the evidence regarding altered HPA-axis and ANS reactivity in children prenatally exposed to high maternal depressive symptoms. A systematic search was conducted in the electronic databases MEDLINE, EMBASE and PsycINFO, for studies published till 25 July 2017. A total of 13 studies comprising 2271 mother-infant dyads were included. None of the studies were suitable for meta-analysis. Risk of bias assessment showed low risk for four studies. Only three studies described an independent association between exposure to high maternal prenatal depressive symptoms and altered stress reactivity in children. There is limited evidence of an independent association between prenatal exposure to maternal depression and altered HPA or ANS reactivity in children.
  • ... However, in this study, we focus on exposures during the prenatal period in order to explore the fetal programming hypothesis. There are several studies showing an association between stressful life events during pregnancy and offspring ADHD (Class et al., 2014;Glover, 2011;Grizenko et al., 2012;Huizink et al., 2007;Kim et al., 2009;Laucht et al., 2000;Li, Olsen, Vestergaard, & Obel, 2010;MacKinnon, Kingsbury, Mahedy, Evans, & Colman, 2018;Motlagh et al., 2010;Park, Cho, Kim et al., 2014;Park, Kim, Kim et al., 2014;Rodriguez & Bohlin, 2005;Ronald, Pennell, & Whitehouse, 2011;Zhu et al., 2015). However, two studies did not find any statistically significant associations between adverse life events during pregnancy and offspring ADHD (Lee, Chang, & Lung, 2006;Rice et al., 2010). ...
    Article
    Full-text available
    Background Prenatal exposure to maternal adverse life events has been associated with offspring ADHD, but the role of familial confounding is unclear. We aimed to clarify if adverse life events during pregnancy are related to ADHD symptoms in offspring, taking shared familial factors into account. Method Data were collected on 34,751 children (including 6,427 siblings) participating in the population‐based Norwegian Mother and Child Cohort Study. During pregnancy, mothers reported whether they had experienced specific life events. We assessed ADHD symptoms in five‐year‐old children with the Conners’ Parent Rating Scale–Revised: short form. We modeled the associations between life events and mean ADHD scores with ordinary linear regression in the full cohort, and with fixed‐effect linear regression in sibling comparisons to adjust for familial confounding. Results Children exposed to adverse life events had higher ADHD scores at age 5, with the strongest effect observed for financial problems (mean differences 0.10 [95% CI: 0.09, 0.11] in adjusted model), and the weakest for having lost someone close (0.02 [95% CI 0.01, 0.04] in adjusted model). Comparing exposure‐discordant siblings resulted in attenuated estimates that were no longer statistically significant (e.g. mean difference for financial problems −0.03 [95% CI −0.07, 0.02]). ADHD scores increased if the mother had experienced the event as painful or difficult, and with the number of events, whereas sibling‐comparison analyses resulted in estimates attenuated toward the null. Conclusions These results suggest that the association between adverse life events during pregnancy and offspring ADHD symptoms is largely explained by familial factors.
  • ... 2 Maternal prenatal stress has been conceptualized and measured in various ways, but the most common has been to measure maternal anxiety or depression during pregnancy. 5 To date, a vast body of literature has examined the impact of maternal prenatal stress on perinatal and postnatal health outcomes. Given the variability in results, several meta-analyses have been performed in an attempt to clarify patterns within this area of research. ...
  • ... Gunnar, 2010), as well as alterations in brain functional and structural development (e.g., cortical thinning, amygdala-prefrontal connectivity), and related problems in attention and emotion regulation have been reported (Dunkel Schetter & Tanner, 2012;Posner et al., 2016;Sandman, Class, et al., 2016). Moreover, higher rates of symptoms of depression and anxiety as well as attention deficit hyperactivity disorder and conduct disorders have been reported in children with prenatal stress (PS) exposure (Glover, 2011(Glover, , 2015Van den Bergh et al., 2017). The underlying biological mechanisms are not well understood (Sandman, Class, et al., 2016; but possibly include exposure to inflammatory cytokines and/or excessive levels of cortisol in utero (Glover & Capron, 2017) that lead to altered fetal growth and changes in structure and functions of the central nervous systems (Van den Bergh et al., 2017). ...
    Article
    We examined how infants’ attentional disengagement from happy, fearful, neutral, and phase‐scrambled faces at 8 months, as assessed by eye tracking, is associated with trajectories of maternal depressive symptoms from early pregnancy to 6 months postpartum (decreasing n = 48, increasing n = 34, and consistently low symptom levels n = 280). The sample (mother–infant dyads belonging to a larger FinnBrain Birth Cohort Study) was collected between 5/2013–6/2016. The overall disengagement probability from faces to distractors was not related to maternal depressive symptoms, but fear bias was heightened in infants whose mothers reported decreasing or increasing depressive symptoms. Exacerbated attention to fearful faces in infants of mothers with depressive symptoms may be independent of the timing of the symptoms in the pre‐ and postnatal stages.
  • ... There is robust evidence that prenatal psychological distress is harmful to the mother, the fetus, and, eventually, the child. Indeed, maternal stress during pregnancy has been associated with serious negative outcomes including poor maternal psychosocial functioning, 1 parenting difficulties, 1 lower infant birthweight, 2 earlier infant gestational age, 2 offspring psychopathology, 3 alterations in brain development, 4 and poorer socioemotional 5 and cognitive development. 6 The detrimental effects of prenatal maternal psychological distress would not be limited to the most vulnerable populations as higher levels of anxiety and depression during pregnancy would be linked to alterations in fetal and infant brain development even in women with low-risk pregnancies, high levels of education, and high socioeconomic status. ...
    Article
    Introduction: Prenatal maternal distress has a negative impact on the course of pregnancy, fetal development, offspring development and later psychopathologies. The study aimed to determine the extent to which the Coronavirus disease 2019 (COVID-19) pandemic may aggravate pregnant women prenatal distress and psychiatric symptomatology. Material and methods: Two cohorts of pregnant volunteer women were evaluated, one that was recruited before the COVID-19 pandemic (n=496) through advertisements in prenatal clinics in Quebec, Canada, from April 2018 to March 2020; the other (n=1258) was recruited online during the pandemic from April 2 to April 13 2020. Prenatal distress and psychiatric symptomatology were measured with the Kessler Distress Scale (K10), Post-traumatic Checklist for DSM-5 (PCL-5), Dissociative Experiences Scale (DES-II) and Positive and Negative Affect Schedule (PANAS). Results: The 1754 pregnant women (Mage =29.27, SD=4.23) were between 4 and 41 gestational weeks (M=24.80, SD=9.42), were generally educated (91.3% had post-high school training) and financially well-resourced (85.3% were above the low-income cut-off). A multivariate analysis of covariance controlling for age, gestational age, household income, education and lifetime psychiatric disorders showed a large effect size (ES) in the difference between the two cohorts on psychiatric symptoms (Wilks' λ=0.68, F6,1400 =108.50, p < 0.001, partial η2 = 0.32). According to post-hoc analyses of covariance, the COVID-19 women reported higher levels of depressive and anxiety symptoms (ES=0.57), dissociative symptoms (ES=0.22 and 0.25), symptoms of post-traumatic stress disorder (ES=0.19), negative affectivity (ES = 0.96) and less positive affectivity (ES=0.95) than the pre-COVID-19 cohort. Women from the COVID-19 cohort were more likely than pre-COVID-19 women to present clinically significant levels of depressive and anxiety symptoms [OR=1.94, χ2(1)=10.05, p=.002]. Multiple regression analyses indicated that COVID-19 pregnant women having a previous psychiatric diagnosis or low income would be more prone to elevated distress and psychiatric symptoms. Conclusions: Pregnant women assessed during the COVID-19 pandemic reported more distress and psychiatric symptoms than pregnant women assessed before the pandemic, mainly in the form of depression and anxiety symptoms. Given the harmful consequences of prenatal distress on mothers and offspring, the presently observed upsurge of symptoms in pregnant women calls for special means of clinical surveillance.
  • ... Following on from this concept, some researchers [13] have hypothesised that maternal mental state during pregnancy may programme the foetal brain and make the child more prone to certain behaviours; for example, maternal prenatal depression has been linked to behavioural problems in toddlers [14]. Prenatal stress has been associated with increased impulsivity, lower cognitive performance, conduct disorder and hyperactivity symptoms in children [15]. Putative biological pathways have been identified for these effects. ...
    Article
    The objective of this study is to explore the association between maternal somatic anxiety in pregnancy and hyperactivity symptoms and ADHD diagnosis in children. Data from the Avon Longitudinal Study of Parents and Children cohort were used to examine the association between somatic anxiety symptoms in pregnancy measured with five items of the Crown-Crisp Experiential Index, ADHD diagnosis in children at 7.5 and 15 years (obtained with the Development and Well-Being Assessment-DAWBA) and hyperactivity at 4 and 16 years (measured with the Strengths and Difficulties Questionnaire hyperactivity subscale-SDQ). Maternal somatic anxiety was associated with ADHD diagnosis at age 7.5 [crude OR = 1.87 (95% CI = 1.21–2.91)], adjusted model [OR = 1.57 (95% CI = 0.99–2.48)]. There was no evidence of association with ADHD at 15: crude OR = 2.27 (95% CI = 0.90–5.71), adjusted OR = 1.65 (95% CI = 0.63–4.35). An association was found at 4 and 16 with the SDQ hyperactivity subscale: crude OR at 4: 1.70 (95% CI =1.37–2.11), adjusted OR = 1.34 (95% CI = 1.07–1.69); crude OR at 16: 1.95 (95% CI = 1.47–2.58), adjusted OR = 1.62 (95% CI = 1.21–2.17).Thus, there was evidence for an association between maternal somatic anxiety in pregnancy and increased hyperactivity symptoms (SDQ) at 4 and 16. There was no association with ADHD diagnosis.
  • ... On a more functional level, it has been hypothesised that stress, malnutrition and environmental adversities integrate into the development, since they contain valuable information for demands later encountered in life (Agrawal et al 1999, Heiming et al 2011, Low et al 2012. Studies also highlight the fact that mild postnatal stress increases later life stress resilience in mice (Glover 2011), while short periods of handling (Weiner et al 1987) or short separations from the mother for up to 15 minutes in length, provoke an increase in maternal care behaviour in an attempt to compensate for the disturbance (Millstein et al 2006, Moles et al 2004. Other studies again show that more severe forms of early-life stress, such as the Maternal Separation and Early Weaning paradigm presented by (George et al 2010) are better suited to produce an early strong adverse environment. ...
    Thesis
    Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are disorders of mostly unknown etiopathogenesis, for which both genetic and environmental influences are expected to contribute to the phenotype observed in patients. Changes at all levels of brain function, from network connectivity between brain areas, over neuronal survival, synaptic connectivity and axonal growth, down to molecular changes and epigenetic modifications are suspected to play a key roles in these diseases, resulting in life-long behavioural changes. Genome-wide association as well as copy-number variation studies have linked cadherin-13 (CDH13) as a novel genetic risk factor to neuropsychiatric and neurodevelopmental disorders. CDH13 is highly expressed during embryonic brain development, as well as in the adult brain, where it is present in regions including the hippocampus, striatum and thalamus (among others) and is upregulated in response to chronic stress exposure. It is however unclear how CDH13 interacts with environmentally relevant cues, including stressful triggers, in the formation of long-lasting behavioural and molecular changes. It is currently unknown how the environment influences CDH13 and which long term changes in behaviour and gene expression are caused by their interaction. This work therefore investigates the interaction between CDH13 deficiency and neonatal maternal separation (MS) in mice with the aim to elucidate the function of CDH13 and its role in the response to early-life stress (ELS). For this purpose, mixed litters of wild-type (Cdh13+/+), heterozygous (Cdh13+/-) and homozygous knockout (Cdh13-/-) mice were maternally separated from postnatal day 1 (PN1) to postnatal day 14 (PN14) for 3 hours each day (180MS; PN1-PN14). In a first series of experiments, these mice were subjected to a battery of behavioural tests starting at 8 weeks of age in order to assess motor activity, memory functions as well as measures of anxiety. Subsequently, expression of RNA in various brain regions was measured using quantitativ real-time polymerase chain reaction (qRT-PCR). A second cohort of mice was exposed to the same MS procedure, but was not behaviourally tested, to assess molecular changes in hippocampus using RNA sequencing. Behavioural analysis revealed that MS had an overall anxiolytic-like effect, with mice after MS spending more time in the open arms of the elevated-plus-maze (EPM) and the light compartment in the light-dark box (LDB). As a notable exception, Cdh13-/- mice did not show an increase of time spent in the light compartment after MS compared to Cdh13+/+ and Cdh13+/- MS mice. During the Barnes-maze learning task, mice of most groups showed a similar ability in learning the location of the escape hole, both in terms of primary latency and primary errors. Cdh13-/- control (CTRL) mice however committed more primary errors than Cdh13-/- MS mice. In the contextual fear conditioning (cFC) test, Cdh13-/- mice showed more freezing responses during the extinction recall, indicating a reduced extinction of fear memory. In the step-down test, an impulsivity task, Cdh13-/- mice had a tendency to wait longer before stepping down from the platform, indicative of more hesitant behaviour. In the same animals, qRT-PCR of several brain areas revealed changes in the GABAergic and glutamatergic systems, while also highlighting changes in the gatekeeper enzyme Glykogensynthase-Kinase 3 (Gsk3a), both in relation to Cdh13 deficiency and MS. Results from the RNA sequencing study and subsequent gene-set enrichment analysis revealed changes in adhesion and developmental genes due to Cdh13 deficiency, while also highlighting a strong link between CDH13 and endoplasmatic reticulum function. In addition, some results suggest that MS increased pro-survival pathways, while a gene x environment analysis showed alterations in apoptotic pathways and migration, as well as immune factors and membrane metabolism. An analysis of the overlap between gene and environment, as well as their interaction, highlighted an effect on cell adhesion factors, underscoring their importance for adaptation to the environment. Overall, the stress model resulted in increased stress resilience in Cdh13+/+ and Cdh13+/- mice, a change absent in Cdh13-/- mice, suggesting a role of CDH13 during programming and adaptation to early-life experiences, that can results in long-lasting consequences on brain functions and associated behaviours. These changes were also visible in the RNA sequencing, where key pathways for cell-cell adhesion, neuronal survival and cell-stress adaptation were altered. In conclusion, these findings further highlight the role of CDH13 during brain development, while also shedding light on its function in the adaptation and response during (early life) environmental challenges.
  • ... The possibility that moderate normative PS might buffer the placenta from Superstorm Sandy PS was anticipated by various theories encapsulated under the Developmental Origins of Health and Disease hypothesis (DOHaD) [95], such as Allostatic Load [96], Predictive Adaptive Response [97] and the three-hit concept of vulnerability and resilience [98], which generally conceptualize epigenetic responses as anticipatory adaptations to an environment such as the one the mother experiences during pregnancy. In these models, PS signals an environment that is either impoverished or dangerous and thus programs offspring, especially male offspring, to grow to become smaller (to need less energy), slower in metabolism (to better conserve it), faster to mature and more vigilant, impulsive, aggressive and unemotional (to better fend off competitors and predators) [99]. Additionally, these DOHaD theories can be viewed as consonant with a stress inoculation model [100] in which moderate stress exposure protects the organism from future stress-a model consistent with our results. ...
    Article
    Full-text available
    The placenta plays a central role in the epigenetic programming of neurodevelopment by prenatal stress (PS), but this pathway is not fully understood. It difficult to study in humans because the conditions for intense, traumatic PS are almost impossible to create ethically. This study was able to capitalize on a 2012 disaster that hit New York, Superstorm Sandy, to examine the impact of traumatic stress on placental gene expression while also examining normative PS, and compare the two. Of the 303 expectant mothers participating in the Stress in Pregnancy Study, 95 women were pregnant when Superstorm Sandy struck. During their pregnancy, participants completed self-report measures of PS and distress that were combined, using latent profile analysis, into one global indicator of normative PS. Placental tissue was collected at delivery and frozen for storage. RNA expression was assessed for 40 placental genes known to associate with the stress response system and neurodevelopment in offspring. Results showed that normative PS increased expression of just MECP2, HSD11B2, and ZNF507, whereas Superstorm Sandy PS decreased expression of CDKL5, CFL1, DYRK1A, HSD11B2, MAOA, MAOB, NCOR1, and ZNF507. Interaction analyses indicated that Superstorm Sandy PS was associated with decreased gene expression for the low and high PS group for CFL1, DYRK1A, HSD11B2, MAOA, and NCOR1 and increased expression for the moderate PS group for FOXP1, NR3C1, and NR3C2. This study supports the idea that a moderate amount of normative PS may buffer the impact of traumatic PS, in this case caused by Superstorm Sandy, on placental gene expression, which suggests that the placenta itself mirrors the organism’s ability to develop an epigenetic resilience to, and inoculation from, stress.
  • ... A large body of work has reported an association between perinatal risk factors, including in utero substance exposure, prematurity, and low birthweight, and negative health outcomes across multiple stages of development (McCormick, Litt, Smith, & Zupancic, 2011;Min et al., 2014). These studies are consistent with the fetal origins theory (or "Barker's hypothesis"), which posits that exposure to environmental insults (e.g., maternal substance use, stress) during the period of gestation has significant impacts on a broad range of later health problems (Barker, 2004;Glover, 2011). For example, a large body of evidence has linked prenatal substance exposure to poorer cognitive abilities (e.g., executive functioning; Richardson, Goldschmidt, Larkby, & Day, 2015) and delays in language and visual-motor skills (Singer, Minnes, Min, Lewis, & Short, 2015). ...
    Article
    Infants adopted domestically from foster care often present with prenatal substance exposure and risky birth outcomes such as prematurity and low birth weight. Because few longitudinal studies of foster‐adoptive infants exist, it is unclear how these preplacement risk factors influence development over time. The present study examined associations between perinatal risk factors and developmental outcomes among an ethnically/racially diverse sample of 97 infants in foster care (56% boys) placed into adoptive homes at ages 0–19 months. Relative to population norms, foster‐adoptive infants showed comparable cognitive but lower language and motor functioning at baseline and 1‐year follow‐up. Age‐adjusted language scores significantly improved 1 year following placement, consistent with a developmental “catch‐up” effect. Low birth weight uniquely predicted lower language scores at baseline, but this association was no longer significant at follow‐up. Prenatal substance exposure was associated with lower baseline cognitive scores, but only for infants placed after 6 months of age. In contrast, infants with low birth weight and later placement age (>12 months) showed the most accelerated motor development. Sex differences emerged at follow‐up when predicting motor and language outcomes, suggesting potential sex‐specific pathways of risk. Overall, results support adoption as an early intervention that may buffer vulnerability to perinatal risk on development.
  • ... The prospective association between prenatal anxiety and infant temperament documented herein may be explained using the developmental model of fetal programming, according to which prenatal exposure can prompt long-term developmental responses in the organism, affecting neurobiology and behavior (Egliston et al. 2007;Glover 2011;McCrory et al. 2012). Increased maternal stress hormones, produced by the mother's hypothalamic-pituitary-adrenal (HPA) axis, may impact fetal development of structural and functional neural systems, affecting emotional and behavioral responses in infancy (Egliston et al. 2007;McCrory et al. 2012). ...
    Article
    Full-text available
    Anxiety in the antenatal period is a common experience, associated with adverse consequences for mother and child. Specific types of prenatal anxiety may have unique associations with infant temperament. This study examines the prospective relationships between general prenatal anxiety, fear of childbirth, and specific prenatal anxiety disorders and early infant temperament 8 weeks postpartum. Data were derived from the Akershus Birth Cohort (ABC), a longitudinal cohort study which targeted all women scheduled to give birth at Akershus University Hospital, Norway. Psychometric measures pertained to general prenatal anxiety (Hopkins Symptom Checklist), fear of childbirth (Wijma delivery expectancy questionnaire), screening for manifest prenatal anxiety disorders based on questions from the mini-international neuropsychiatric interview, and difficult infant temperament (Infant Characteristics Questionnaire). The sample for the present study included 2206 women. General prenatal anxiety, fear of childbirth, agoraphobia, generalized anxiety disorder, and specific phobia presented unique significant prospective contributions to difficult infant temperament 8 weeks postpartum. Separate hierarchical regression models indicated that general prenatal anxiety and fear of childbirth provided the strongest unique contributions. Considering the burden on mothers and the potential long-term effects on child development, the findings of this study highlight the importance of screening women for different types of prenatal anxiety in routine obstetric care. Clinical awareness of the condition and its consequences is warranted. Due to the complexity of infant temperament as a construct with various influences, future research should consider mechanisms and influential factors pertaining to the relationship between prenatal anxiety and infant temperament.
  • ... 1 Investigations into common psychiatric disorders have highlighted various early life risk factors, such as prenatal stress, social support, maternal anxiety, early life trauma and childhood temperament. 1,2 However, there is a current gap in the literature regarding potential early life risk factors for personality disorders. Personality disorders have a large personal and societal impact including psychosocial impairment, 3 increased rates of suicide, 4,5 functional impairment 5 and long-term health service use. ...
    Article
    Background Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders. Aims This study investigated potential associations between exposure to prenatal stress and personality disorder in offspring. Method In a subsample ( N = 3626) of a large Finnish birth cohort, we used logistic regression models to examine associations between self-reported maternal stress during pregnancy, collected monthly during antenatal clinic appointments, and personality disorder in offspring. Familial and outcome information were obtained by linking data from the Finnish Hospital Discharge Register and the Finnish Population Register. Results Compared with those unexposed, children exposed to any maternal stress during gestation had three times the odds of developing a personality disorder (odds ratio 3.28, 95% CI 1.75–6.15, P < 0.0001). Those exposed to moderate stress had three times the odds (odds ratio 3.13, 95% CI 1.42–6.88, P = 0.005) and those exposed to severe stress had seven times the odds (odds ratio 7.02, 95% CI 2.08–23.66, P = 0.002) of developing a personality disorder. These associations remained after adjusting for parental psychiatric history, comorbid psychiatric diagnoses, prenatal smoking and antenatal depression. Conclusions Exposure to stress during gestation increases the odds of personality disorder in offspring, independent of other psychiatric disorders. These results suggest the assessment of maternal stress and well-being during pregnancy may be useful in identifying those at greatest risk of developing personality disorder, and highlight the importance of prenatal care for good maternal mental health during pregnancy. Declaration of interest None.
  • ... The HPA axis is activated both during pregnancy and postpartum and changes in its activity have been associated with mothers' emotion, cognition and behavior towards their infants. Mothers' behavior definitely affects the social, emotional and cognitive development of their infants (Glover, 2011). Children of depressed or stressed mothers tend to show low social engagement, less mature regulatory behaviors and more negative emotionality (Feldman et al., 2009;Field, 2017). ...
    Article
    This selective review first describes the involvement of the maternal hypothalamic-pituitary-adrenal (HPA) axis during pregnancy and the postpartum period, and the relation between peripartum HPA axis function and maternal behavior, stress reactivity and emotional dysregulation in human mothers. To provide experimental background to this correlational work, where helpful, animal studies are also described. It then explores the association between HPA axis function in mothers and their infants, under ongoing non-stressful conditions and during stressful challenges, the moderating role of mothers' sensitivity and behavior in the mother-child co-regulation and the effects of more traumatic risk factors on these relations. The overarching theme being explored is that the HPA axis - albeit a system designed to function during periods of high stress and challenge - also functions to promote adaptation to more normative processes, shown in the new mother who experiences both high cortisol and enhanced attraction and attention to and recognition of, their infants and their cues. Hence the same HPA system shows positive relations with behavior at some time points and inverse ones at others. However, the literature is not uniform and results vary widely depending on the number, timing, place, and type of samplings and assessments, and, of course, the population being studied and, in the present context, the state, the stage, and the stress levels of mother and infant.
  • ... Early life experience plays a crucial role in the maturation and fine-tuning of neurocircuitry that drives emotional behavior in adulthood [1][2][3][4][5][6] . Both clinical and preclinical evidence indicates that early life adversity serves as a key risk factor for the development of adult psychopathology, increasing susceptibility to psychiatric disorders like anxiety, major depression and schizophrenia 5,[7][8][9][10] . Stressful experiences in adulthood can produce behavioral alterations that are often transient in nature, however perturbations in the vulnerable perinatal 'critical window' can program lasting changes in emotional behavior [11][12][13] . ...
    Preprint
    Full-text available
    Early adversity is a key risk factor for the development of adult psychopathology, including anxiety, depression and schizophrenia. Rodent models of early adversity program persistent behavioral, molecular, metabolic, and neurophysiological changes. Perturbed signaling via forebrain Gq-coupled neurotransmitter receptors is a common feature across multiple models of early adversity. We addressed whether enhanced Gq-mediated signaling in forebrain excitatory neurons during postnatal life can evoke long-lasting mood-related behavioral changes. Excitatory hM3Dq DREADD-mediated chemogenetic activation of CamKIIα-positive forebrain excitatory neurons during postnatal life (P2-14) increased anxiety- and despair-like behavior, and evoked sensorimotor gating deficits in adulthood. In contrast, chronic chemogenetic hM3Dq DREADD activation of forebrain excitatory neurons in the juvenile or adult window did not evoke any mood-related behavioral alterations, highlighting the criticality of the postnatal temporal window. The enhanced anxiety-, despair- and schizophrenia-like behavioral changes evoked by chronic chemogenetic activation of forebrain excitatory neurons in postnatal life, was accompanied by an increased cortical and hippocampal metabolic rate of glutamatergic and GABAergic neurons in adulthood. Furthermore, animals with a history of postnatal hM3Dq activation exhibited a decline in the expression of activity-dependent and plasticity-associated markers within the hippocampus, along with perturbed hippocampal excitatory and inhibitory currents in adulthood. These results indicate that Gq signaling mediated activation of forebrain excitatory neurons during the critical postnatal window is sufficient to program altered mood-related behavior, as well as metabolic and neurophysiological changes in forebrain glutamate and GABA systems, recapitulating specific aspects of the consequences of early adversity.
  • ... Within emerging Developmental Origins of Health and Disease https://doi.org/10.1016/j.jad.2019.08.003 (DOHaD) literature (Wadwha et al., 2009;Gluckman et al., 2011), there is a growing emphasis on associations between prenatal stress-including depression and anxiety as responses to stress-and early development, using 'fetal programming' models. In general, fetal programming refers to various prenatal changes to maternal physiology (e.g., in response to stress, disease, substance use), which can alter offspring phenotypes and affect development across the lifespan (Glover, 2011;Hochberg et al., 2011). Despite forthcoming evidence for programming effects, there is significant heterogeneity in outcomes, wherein certain children are adversely affected, whereas others do not appear to experience long-term consequences (Glover, 2011). ...
    Article
    Background: The severity and treatment of depression/anxiety during pregnancy and postpartum has important implications for maternal and child well-being. Yet, little is known about prenatal SSRI use and early child socioemotional development. This study explores effects of prenatal SSRI exposure, and pre- and postnatal internalizing symptoms on trajectories of infant temperament, identifying potential differences for boys and girls. Methods: Using latent growth models, sex differences in infant temperament trajectories from 3- to 10-months were examined in relation to prenatal and postpartum internalizing symptoms and prenatal SSRI exposure among 185 mother-infant dyads. Results: For girls, prenatal internalizing symptoms were associated with greater initial distress to limitations, and lower duration of orienting, smiling/laughter, and soothability. Postnatal symptoms predicted slower decreases in girls' duration of orienting. SSRI exposure predicted decreases in distress to limitations and slower increases in smiling and laughter. For boys, maternal internalizing symptoms did not generally affect temperament profiles. SSRI exposure was associated with higher initial activity level and slower declines in distress to limitations. Limitations: Only parent-report indicators of infant temperament across 10 months of infancy were provided. Maternal internalizing symptoms were measured at discrete times during pregnancy and postpartum, with no analysis of changes in symptoms across time. Conclusions: Prenatal SSRI treatment, and both prenatal and postpartum internalizing symptoms, exert unique effects on infant temperament. Overall, the present study suggests sex-dependent fetal programming effects that should be further evaluated in future research. Results have implications for perinatal mental health treatment and perceived impacts on child socioemotional development.
  • ... Some studies indicate that emotional wellbeing of women enhances physical health of children and it has been the main concern of different researchers (Berghet al., 2008;Weinstock, 2008;DiPietro et al., 2008;O'Donnel et al., 2009;Glover, 2011;Lange & Randler, 2011). Moreover, it is also evident that the emotional stresses of women reduce physical growth of children (Rondó et al., 2003). ...
    Article
    Full-text available
    Women well-being has number of socioeconomic and developmental implications. Early child development is directly linked with well-being of mothers and educated women demand lower children. However, the existing literature hardly focused this area, therefore, the current study has investigated the impact of women wellbeing on fertility and early child development. For this purpose, this study constructed women well-being index to measure the well-being of the women by using four dimensions, economic well-being of women, social well-being of women, political awareness of women and satisfaction of women in different aspects of life. Moreover, early child development index has considered as proxy for child development which covers four dimensions of early child development, literacy-numeracy of children, physical growth of children, learning of children and socio-emotional development of children. In this connection, the data was collected from thirty-six districts across the Punjab province, Pakistan. By applying descriptive and regression analysis, the study found that women well-being has positive association with all domains of early child development. However, women well-being and its dimensions have negative relationship with fertility. Therefore, improvement in well-being of women may a suitable strategy especially for developing economies to enhance early child development and to reduce demand of children.
  • ... Cortisol, a hormone produced by the maternal hypothalamo-pituitary-adrenal (HPA) axis, is secreted in response to stressors that she experiences and in association with psychological conditions, including depression (Field et al., 2004;Sandman, Wadhwa, Chicz-DeMet, Porto, & Garite, 1999). In utero maternal cortisol can cross the placenta to the fetal compartment and may activate a cascade of epigenetic, hormonal, and immune changes affecting the development of the central and peripheral nervous systems (Chrousos, 1992;Glover, 2011;Van den Bergh, Mulder, Mennes, & Glover, 2005;Wadhwa, Sandman, & Garite, 2001;Zhang, Li et al., 2018). Acute prenatal maternal stress (PNMS) that pregnant women experience, such as natural disasters, and/or mental health issues including depression may therefore inadvertently increase their offspring's risk for suboptimal development. ...
    Article
    We set out to examine the relations between prenatal exposure to the natural disaster Superstorm Sandy, maternal depression, and offspring electrodermal activity (EDA). EDA was measured via skin conductance response (SCR) magnitude in 198 children (M = 42.54 months, SD = 12.76) during a startle paradigm. In keeping with prior research, we expected prenatal depression to be associated with hyporeactive EDA and prenatal stress to be associated with hyperreactive EDA. SCR magnitude was lower in children prenatally exposed to depression alone, when compared to Superstorm Sandy, and controls. SCR magnitude of children prenatally exposed to both maternal depression and the storm was lower than that of all other groups. Our results emphasize the influence of maternal prenatal mental health, support targeted risk assessment for children who experienced an adverse prenatal environment, and highlight the need for a deeper understanding of the interactions between maternal mood and stress on the developing child.
  • ... For instance, mild dose of stress increases both physical maturation and anxiety. These changes are better to be called evolutionary adaptation, rather than "good" or "bad" [21]. Other studies have demonstrated different results evaluating the effects of maternal stress on the offspring brain and motor development. ...
    Article
    Stressful episodes are common during early-life and may have a wide range of negative effects on both physical and mental status of the offspring. In addition to various neurobehavioral complications induced by prenatal stress (PS), seizure is a common complication with no fully explained cause. In this study, the association between PS and seizure susceptibility was reviewed focusing on sex differences and various underlying mechanisms. The role of drugs in the initiation of seizure and the effects of PS on the nervous system that prone the brain for seizure, especially the hypothalamic-pituitary-adrenal (HPA) axis, are also discussed in detail by reviewing the papers studying the effect of PS on glutamatergic, gamma-aminobutyric acid (GABA)ergic, and adrenergic systems in the context of seizure and epilepsy. Finally, epigenetic changes in epilepsy are described, and the underlying mechanisms of this change are expanded. As the effects of PS may be life-lasting, it is possible to prevent future psychiatric and behavioral disorders including epilepsy by preventing avoidable PS risk factors.
  • ... According to the fetal origins hypothesis, the origins of many adults' physical and mental health outcomes can be traced back to the in utero period, when rapid changes in the structure and function of the fetal brain and body take place based on the intrauterine and extrauterine environments. 12 In this study, we identified for the first time that any prenatal exposure to earthquake during gestation has an enduring deleterious effect on schizophrenia in adulthood, using the GTE as a natural experiment. Data for this study were gleaned from a large representative sample of the most recent national population-based survey on disability in China. ...
    Article
    Full-text available
    Background Maternal exposure to major stressors during pregnancy has been found to increase the risk of neurodevelopmental, cognitive and psychiatric disorders in the offspring. However, the association between prenatal exposure to earthquake and the risk of adult schizophrenia has yet to be examined. Aims To explore the potential long-term effects of prenatal exposure to maternal stress on the risk of schizophrenia in adulthood, using the Great Tangshan Earthquake in 1976 as a natural experiment. Method We obtained data from the Second China National Sample Survey on Disability, and analysed 94 410 Chinese individuals born between 1975 and 1979. We obtained difference-in-differences estimates of the earthquake effects on schizophrenia by exploiting temporal variation in the timing of earthquake exposure across four birth cohorts born between 1975 and 1979, along with geographical variation in earthquake severity at the prefecture level. Schizophrenia was ascertained by psychiatrists using the ICD-10 classification. Earthquake severity was measured by seismic intensity. Results Earthquake cohort who experienced prenatal exposure to felt earthquake had higher risk of schizophrenia (odds ratio, 3.38; 95% CI 1.43–8.00) compared with the unexposed reference cohort. After specifying the timing of exposure by the trimester of pregnancy, prenatal exposure to felt earthquake during the first trimester of pregnancy increased the risk of adulthood schizophrenia significantly (odds ratio, 7.45; 95% CI 2.83–19.59). Conclusions Prenatal (particularly early pregnancy) exposure to maternal stress after a major disaster substantially affects the mental health of Chinese adults. Declaration of interest None.
  • ... 5,6 Furthermore, the effects seem to be nonspecific in that prenatal stress increases the offspring's early risk for both internalizing problems (especially, anxiety and depression) and externalizing problems (such as attention-deficit/hyperactivity disorder and conduct disorder). 7,8 These effects persist long-term and are also present in low-and middle-income countries. 1,9 However, the synthesis of research findings is complicated by the diversity of measures used to characterize prenatal maternal affective symptoms, which makes it hard to pinpoint whether there are specific components that are most strongly linked with offspring psychopathology or might show specific associations with child internalizing or externalizing behavior. ...
    Article
    Full-text available
    Objective Few studies have attempted to identify how distinct dimensions of maternal prenatal affective symptoms relate to offspring psychopathology. We defined latent dimensions of women’s prenatal affective symptoms and pregnancy-specific worries to examined their association with early offspring psychopathology in three prenatal cohorts. Method Data were used from three cohorts of the DREAM-BIG consortium: Avon Longitudinal Study of Parents and Children (ALSPAC [N=12,515]), Generation R (N=6,803), and the Canadian prenatal cohort Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN [N=578]). Maternal prenatal affective symptoms and pregnancy-specific worries were assessed using different measures in each cohort. Through confirmatory factor analyses we determined whether comparable latent dimensions of prenatal maternal affective symptoms exist across the cohorts. We used structural equation models to examine cohort-specific associations between these dimensions and offspring psychopathology at 4-8 years of age (general psychopathology, specific internalizing and externalizing previously derived using confirmatory factor analyses). Cohort-based estimates were meta-analyzed using inverse variance-weighing. Results Four prenatal maternal factors were similar in all cohorts: a general affective symptoms factor and three specific factors—an anxiety/depression factor; a somatic factor; and a pregnancy-specific worries factor. In meta-analyses, both the general affective symptoms factor and pregnancy-specific worries factor were independently associated with offspring general psychopathology. The general affective symptoms factor was further associated with offspring specific internalizing problems. There were no associations with specific externalizing problems. Conclusion These replicated findings of independent and adverse effects for prenatal general affective symptoms and pregnancy-specific worries on child mental health support the need for specific interventions in pregnancy.
  • ... Este tipo de programación fetal prepara al niño para el entorno en que se van a encontrar ellos mismos. Esta adaptación lo hace mucho más pronto a reaccionar, ser más vigilante, distraído en su atención con mayor percepción de peligro, impulsivo con mayor exploración, tener desórdenes de conducta con deseo de romper las reglas, y agresivo para luchar contra intrusos (16) . Suelen ser niños más susceptibles a llorar, a estresarse, a sentir ansiedad. ...
    Article
    Full-text available
    INFLUENCE OF MATERNAL STRESS AND DEPRESSION ON CHILD DEVELOPMENT SUMMARY The manner in which the fetus develops in the uterus depends on the status of the mother, their food, their environment and their emotions. Studies in laboratory animals have shown that prenatal stress causes serious disturbances in the CNS, particularly the hypothalamic adrenal axis (HPA) in the hormonal response to stress. Several studies, including several natural experiments, have found a significant association between antenatal maternal anxiety or stress problems and different cognitive, behavioral, and emotional language in children. Among the risk factors for psychological disorders present during pregnancy are personal or family history of psychiatric illness or drug use, past personal history of sexual, physical or emotional, and a past history of depression, which is the factor that strongly predicts antenatal depressive symptoms. The maternal stress and anxiety can affect the fetus throughout pregnancy but do so in different ways according to the stage of gestation at which it is and which areas of the brain are developing. Why it is so necessary to research and develop programs of prevention, intervention and support to reduce the levels of stress, anxiety or depression during pregnancy and prevent adverse effects in a clinically significant proportion of children. Rev. peru. pediatr. 65 (3) 2012
  • Article
    Domestic abuse and mental health disorders are particularly dangerous during the perinatal period, due to their effects on both the mother and the developing fetus. Furthermore, domestic violence and mental health appear to be linked, which can result in these issues being passed down through generations. In order for health professionals to respond efficaciously, pre-registration and ongoing training is needed on how to ask, respond, provide support and refer women on to appropriate supportive agencies. High-quality research is also needed to improve outcomes.
  • Article
    Objective Exposure to prenatal stress is a ubiquitous and non‐specific risk factor for adverse outcomes in adulthood. In this study, we examined associations between exposure to subjective maternal stress during pregnancy and subsequent diagnosis of psychiatric disorders in offspring. Method This study used the Helsinki Longitudinal Temperament Cohort, a prospective birth cohort of individuals born between July 1st, 1975 and June 30th, 1976 in Helsinki, Finland. The sample for this study comprised 3626 infants whose mothers had completed health and well‐being assessments during pregnancy which included a measure of self‐reported stress. We ran logistic regressions to assess potential associations between prenatal stress and offspring psychiatric disorder in adulthood, identified through the Finnish Hospital Discharge Register. Results Individuals whose mothers reported stress during pregnancy had significantly greater odds of developing a psychiatric disorder (OR = 1.41, 95% CI = 1.10 – 1.81) particularly a mood disorder (OR= 1.67, 95% CI = 1.10 – 2.54). These associations remained after adjusting for parental psychiatric history, and other prenatal factors. Conclusions Individuals exposed to prenatal stress had significantly increased risk of developing psychiatric disorders later in life. This finding highlights the importance of supporting the mental health and emotional well‐being of women during pregnancy. This article is protected by copyright. All rights reserved.
  • Article
    Objectives The purpose of this study was to conduct a long-term, population-based, epidemiologic study of psychiatric disorders in mothers of children with attention-deficit/hyperactivity disorder (ADHD). Methods Subjects included mothers of 306 childhood incident cases of ADHD and mothers of 617 age/gender matched controls from a 1976–1982 birth cohort. Results Compared to mothers of controls, mothers of children with ADHD were significantly more likely to be diagnosed prior to the child’s birth with a depressive disorder (adjusted odds ratio (aOR), 3.1; 95% confidence interval (CI), 1.3–7.7), an adjustment disorder (aOR, 8.1; 95% CI, 1.7–39.5), or any psychiatric disorder (aOR, 2.5; 95% CI, 1.61–4.7) and were likewise significantly more likely to be diagnosed with a de novo (i.e., first diagnosed after the child’s birth) depressive disorder (adjusted hazard ratio (aHR), 1.7; 95% CI, 1.2–2.4), de novo adjustment disorder (aHR, 2.0; 95% CI, 1.4–2.7), or any de novo psychiatric disorder (aHR, 1.7; 95% CI, 1.4–2.2) during the 21 years after the child’s birth. Conclusions This study provides an opportunity to study the natural occurrence of psychiatric disorders in mothers of children with ADHD and suggests that the likelihood of having a child with ADHD is associated with maternal psychopathology both before and after the birth. This adds to existing knowledge of maternal psychopathology for children with ADHD and has implications for screening and monitoring. Future research is needed to clarify the role that both genetic and environmental risk factors play in the increased rates of psychopathology in mothers of children with ADHD.
  • Book
    Cambridge Core - Philosophy of Science - What Biological Functions Are and Why They Matter - by Justin Garson
  • Article
    Extensive evidence now shows that adversity during the perinatal period is a significant risk factor for the development of neurodevelopmental disorders long after the causative event. Despite stemming from a variety of causes, perinatal compromise appears to have similar effects on the developing brain, thereby resulting in behavioural disorders of a similar nature. These behavioural disorders occur in a sex‐dependent manner, with males affected more by externalizing behaviours such as attention deficit hyperactivity disorder (ADHD) and females by internalizing behaviours such as anxiety. Regardless of the causative event or the sex of the offspring, these disorders may begin in childhood or adolescence but extend into adulthood. A mechanism by which adverse events in the perinatal period impact later in life behaviour has been shown to be the changing epigenetic landscape. Methylation of the GAD1/GAD67 gene, which encodes the key glutamate‐to‐GABA synthesizing enzyme Glutamate Decarboxylase 1, resulting in increased levels of glutamate is one epigenetic mechanism that may account for a tendency towards excitation in disorders such as ADHD. Exposure of the fetus or the neonate to high levels of cortisol may be the mediator between perinatal compromise and poor behavioural outcomes as evidence suggests that increased glucocorticoid exposure triggers widespread changes in the epigenetic landscape. This review summarises the current evidence and recent literature about the impact of various perinatal insults on the epigenome and the common mechanisms that may explain the similarity of behavioural outcomes that occur following diverse perinatal compromise.
  • Chapter
    Es besteht ein wechselseitiger Zusammenhang zwischen Borderline-Persönlichkeitsstörung (BPS), Trauma und Traumafolgestörungen, insbesondere der Posttraumatischen Belastungsstörung (PTBS). In diesem Kapitel werden zunächst die aktuellen Klassifikationen (ICD, DSM), ätiologischen Modelle, Prävalenzen und Komorbiditäten der BPS sowie der PTBS dargestellt. Anschließend werden relevante Befunde zum Zusammenhang zwischen BPS und PTBS hinsichtlich Genetik, Stressverarbeitung, struktureller und funktioneller Neuroanatomie und Bindungsverhalten diskutiert. Außerdem wird die Rolle von Kindheitstrauma für die Ätiologie der BPS erläutert, und Befunde, die auf ein erhöhtes Risiko von BPS-Patienten für traumatische Erlebnisse hinweisen, werden berichtet. Abschließend werden die komplexe PTBS und die Developmental Trauma Disorder (DTD) als neue diagnostische Konzepte, die den Zusammenhang zwischen BPS und PTBS widerspiegeln, beschrieben.
  • Article
    Prenatal developmental plasticity in response to various environmental and social adversities can affect multiple aspects of offspring phenotype including social behavior strategies with effects that can last into adulthood. Here, we (1) identify adaptive social behavior strategies and their underlying mechanisms as potential targets of developmental plasticity in primates, (2) derive predictions about social behavior outcomes of prenatal adversity from different types of evolutionary models, (3) review the primate evidence for prenatal stress effects on offspring cognitive function, social, and non-social behavior, and (4) discuss avenues for future research. The scarce evidence currently available points towards increased distress behavior, particularly in infant offspring, and reductions of activity, exploration, and affiliative behavior in response to experimental prenatal adversity. Not all effects are stable, the results do not replicate well, and, for the most part, the current data cannot be used to test predictions of evolutionary models because relevant aspects of social behavior were not quantified and not assessed in the complex social environments they evolved for. More comprehensive research in developmental plasticity needs to incorporate sex differences and the interaction of effects from different sensitive periods including adolescence. Moreover, future research needs to assess the role of social buffering in mediating intergenerational effects and trade-offs between the pace of life and social cognitive performance.
  • Article
    Full-text available
    Sex-dependent effects of mismatched prenatal-postnatal maternal conditions are predicted by combining two evolutionary hypotheses: that foetal conditions provide a forecast of likely postnatal environments (Predictive Adaptive Response), and that the female foetus is better adapted than the male to maternal adversity (Trivers-Willard hypothesis). Animal studies have implicated glucocorticoid mechanisms modifiable by effects of postnatal tactile stimulation on glucocorticoid receptor gene expression. In this study we examined behavioural predictions in humans based on these evolutionary and epigenetic models. Mothers in a general population cohort provided self-reported anxiety scores at 20 weeks pregnancy, and at 9 weeks, 14 months and 3.5 years postpartum, and frequency of infant stroking at 9 weeks. Mothers and teachers reported child symptoms at 7 years. SEM models with maximum-likelihood estimates made use of data from 887 participants. There was a three-way interaction between prenatal and postnatal anxiety and maternal stroking in the prediction of irritability, seen only in girls. This arose because lower maternal stroking was associated with higher irritability, only in the mismatched, low-high and high-low maternal anxiety groups. We provide evidence that mechanisms likely to have evolved well before the emergence of humans, contribute to the development of children’s emotionality and risk for depression.
  • Article
    Full-text available
    Background: Self-reported maternal mood symptoms during pregnancy have been related to poor birth outcomes, including low birth weight, increased risk of premature delivery, and pre-eclampsia among pregnant women. A non-pharmacological method is needed to overcome mood symptoms such as anxiety during pregnancy. Purpose: This study aimed to evaluate the effects of yoga relaxation on anxiety levels among pregnant women at the third trimester. Methods: This study employed a quasi-experimental research design and involved 30 pregnant women at the third trimester who were equally divided into two groups. The levels of anxiety were measured by using Hamilton Anxiety Rating Scale (HARS). Data were analysed using the independent t-test and the paired sample t-test. Results: The results showed that there was a significant difference in the anxiety levels before and after the intervention in the experimental group (t=7.56, p=0.005), and there was a significant difference in the anxiety levels after the intervention between the experimental and control group (t=-9.289, p=0.005). Conclusion: Yoga relaxation had an effect on reducing anxiety levels among pregnant women at the third trimester. It is expected that pregnant women use yoga relaxation to decrease anxiety.
  • Article
    Full-text available
    Background: Childhood obesity presents a significant public health challenge globally. The period from conception to two years after birth, the first 1000 days, represents a critical period during which the experience of maternal stress may be related to the development of childhood obesity. Research to date suggests some positive associations between maternal stress during the first 1000 days and childhood obesity, but findings are inconsistent and have not yet been comprehensively synthesised. The purpose of this review is to systematically examine the association between maternal stress during the first 1000 days and the risk of child overweight and obesity. Methods: The following electronic databases will be searched from inception using a detailed search strategy: the Cochrane Library, MEDLINE, PsycINFO, EMBASE, CINAHL, Maternity and Infant Care, and Web of Science. Cohort, case-control, and cross-sectional studies examining maternal stress during the first 1000 days and child overweight and obesity up to the age of 10 years will be included. Titles, abstracts and full articles will be screened by two investigators independently to identify eligible studies. A standardised data extraction form will be used to extract data including: study design; maternal stress exposure; child outcome; exclusion criteria; participant characteristics; and assessment methods. The Cochrane Collaboration’s bias classification tool for observational studies will be used to assess study quality. This protocol is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol (PRISMA-P) checklist, and the systematic review will be conducted and reported following the PRISMA checklist. If possible, random effects models will be used to perform meta-analyses. Ethics and dissemination: Ethical approval is not required for this study as it will not involve conducting experimental research, nor include identifying personal data. The systematic review will be disseminated in peer-reviewed journals. PROSPERO registration number:CRD42018100363
  • Article
    Guided primarily by life history theory, this study was designed to identify how and why early exposure to caregiver intimate relationship instability uniquely predicts children's externalizing symptoms in the context of other dimensions of unpredictability characterized by residential and parental job transitions. Participants included 243 preschool children (M age = 4.60 years) and their mothers who participated in 3 annual measurement occasions (i.e., preschool, kindergarten, first grade). Supporting the first link in the hypothesized mediational chain, the results of structural equation modeling analyses indicated that caregiver intimate relationship instability uniquely predicted a pattern of response processes over a 1-year period characterized by negative family representations, dominant interpersonal strategies for regulating resources, and diminished task persistence. Latent difference score analyses of each of these response processes over the 1-year period, in turn, uniquely predicted a multiinformant (i.e., mother, teacher, experimenter) assessment of children's externalizing symptoms over a 2-year period. Mediational findings were robust after accounting for the negligible roles of residential and occupational changes as simultaneous predictors. Results are interpreted in the context of how they inform and support life history theory as well as other conceptual (e.g., attachment and emotional security theory) models.
  • Article
    Full-text available
    Background: Childhood obesity presents a significant public health challenge globally. The period from conception to two years after birth, the first 1000 days, represents a critical period during which the experience of maternal stress may be related to the development of childhood obesity. Research to date suggests some positive associations between maternal stress during the first 1000 days and childhood obesity, but findings are inconsistent and have not yet been comprehensively synthesised. The purpose of this review is to systematically examine the association between maternal stress during the first 1000 days and the risk of child overweight and obesity. Methods: The following electronic databases will be searched from inception using a detailed search strategy: the Cochrane Library, MEDLINE, PsycINFO, EMBASE, CINAHL, Maternity and Infant Care, and Web of Science. Cohort, case-control, and cross-sectional studies examining maternal stress during the first 1000 days and child overweight and obesity up to the age of 10 years will be included. Titles, abstracts and full articles will be screened by two investigators independently to identify eligible studies. A standardised data extraction form will be used to extract data including: study design; maternal stress exposure; child outcome; exclusion criteria; participant characteristics; and assessment methods. The Cochrane Collaboration’s bias classification tool for observational studies will be used to assess study quality. This protocol is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol (PRISMA-P) checklist, and the systematic review will be conducted and reported following the PRISMA checklist. If possible, random effects models will be used to perform meta-analyses. Ethics and dissemination: Ethical approval is not required for this study as it will not involve conducting experimental research, nor include identifying personal data. The systematic review will be disseminated in peer-reviewed journals. PROSPERO registration number:CRD42018100363
  • Chapter
    Attention Deficit Hyperactivity Disorder (AD/HD) is among the most common behavioral-developmental disorders, affecting 5–15% of children in developed countries. This rate has risen rapidly in the past 20 years as a result of better recognition, more treatment options, and perhaps an actual increase in prevalence. AD/HD is likely to be common in developing countries as well, although less frequently recognized as a medical condition. As awareness of developmental problems grows and life-threatening infectious diseases decline, physicians in developing countries will be called upon to identify and manage AD/HD. Regardless of setting, diagnosis and management of ADHD must occur at the level of primary care because there are simply not enough sub-specialists available. The hallmarks of AD/HD are readily apparent, and effective and safe medications exist. However, there are many diverse conditions that may mimic the condition or co-exist with it, and it can be difficult to find the right medication and titrate it to the optimal dose, which may change over time. Non-medication treatments can be effective for many of the behaviors that accompany AD/HD, but these require education of parents, children, and teachers. With these complexities in mind, this chapter seeks to present strategies and tools that facilitate efficient and thorough management of AD/HD in the outpatient setting.
Literature Review
  • Article
    Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of developmental plasticity, the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development. Recent observations have shown that impaired growth in infancy and rapid childhood weight gain exacerbate the effects of impaired prenatal growth. A new vision of optimal early human development is emerging which takes account of both short and long-term outcomes.
  • Article
    How often has anyone said after reading a textbook, “Wow, what a great read!”? That is what I just did. Peter Gluckman, along with Alan Beedle and Mark Hanson, have written a wonderful introduction to the principles of evolutionary biology and defined ways in which these principles can be applied to understanding human disease. I would recommend the first part of the book, “Fundamentals of Evolutionary Biology” (150 pp) to any reader, whether medical professional or layperson, interested in a clear, concise, complete, yet eminently readable introduction to modern evolutionary theory. The authors not only manage to give the reader a sense of how human beings are inextricably linked to their evolutionary past—hairless apes, as it were—but also provide examples of traits, such as menstruation, menopause, having unusually fat infants and an unusually short intestinal tract, needing vitamins C and D, that are unique to humans and a few of their ape relatives, and how these create exciting medical puzzles for evolutionary biologists to explain and physicians to treat.
  • Article
    Animal studies suggest that psychological factors may interfere with the development of brain asymmetry during gestation. We evaluated whether psychological exposure in pregnancy was associated with mixed-handedness in the offspring. In a follow-up design study, 824 Danish-speaking women with singleton pregnancies provided information on psychological distress and the occurrence of life events in the early second and third trimesters of pregnancy. Handedness of the children was based on maternal reports when the children were 3 years of age. Among the 419 males and 405 females, 7% and 5% respectively were mixed-handed whereas mixed-handedness was found in 3% of the parents. Psychological distress in the third trimester as well as higher levels of stressful life events were related to a higher prevalence of mixed-handedness in the offspring. About 16% of the women reported more than one life event in the third trimester of pregnancy and among the offspring of these women 11% were mixed-handed (odds ratio=2.3; 95% confidence interval 1.2 to 4.4). Women who at the same time reported a high level of distress and stressful life events, had a three- to four-fold higher prevalence of mixed-handedness in their offspring.
  • Article
    We review a significant body of evidence from independent prospective studies that if a mother is stressed while pregnant, her child is substantially more likely to have emotional or cognitive problems, including an increased risk of attentional deficit/hyperactivity, anxiety, and language delay. These findings are independent of effects due to maternal postnatal depression and anxiety. We still do not know what forms of anxiety or stress are most detrimental, but research suggests that the relationship with the partner can be important in this respect. The magnitude of these effects is clinically significant, as the attributable load of emotional/behavioral problems due to antenatal stress and/or anxiety is approximately 15%. Animal models suggest that activity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal end-product cortisol are involved in these effects in both mother and offspring. The fetal environment can be altered if stress in the mother changes her hormonal profile, and in humans, there is a strong correlation between maternal and fetal cortisol levels. However, many problems remain in understanding the mechanisms involved in this interaction. For example, maternal cortisol responses to stress decline over the course of pregnancy, and earlier in pregnancy, the link between maternal and fetal cortisol is less robust. It is possible that the effects of maternal anxiety and stress on the developing fetus and child are moderated by other factors such as a maternal diet (e.g., protein load). It is suggested that extra vigilance or anxiety, readily distracted attention, or a hyper-responsive HPA axis may have been adaptive in a stressful environment during evolution, but exists today at the cost of vulnerability to neurodevelopmental disorders.
  • Article
    Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of developmental plasticity, the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development. Recent observations have shown that impaired growth in infancy and rapid childhood weight gain exacerbate the effects of impaired prenatal growth. A new vision of optimal early human development is emerging which takes account of both short and long-term outcomes.
  • Article
    Full-text available
    This article reviews the evolutionary origins and functions of the capacity for anxiety, and relevant clinical and research issues. Normal anxiety is an emotion that helps organisms defend against a wide variety of threats. There is a general capacity for normal defensive arousal, and subtypes of normal anxiety protect against particular kinds of threats. These normal subtypes correspond somewhat to mild forms of various anxiety disorders. Anxiety disorders arise from dysregulation of normal defensive responses, raising the possibility of a hypophobic disorder (too little anxiety). If a drug were discovered that abolished all defensive anxiety, it could do harm as well as good. Factors that have shaped anxiety-regulation mechanisms can explain prepotent and prepared tendencies to associate anxiety more quickly with certain cues than with others. These tendencies lead to excess fear of largely archaic dangers, like snakes, and too little fear of new threats, like cars. An understanding of the evolutionary origins, functions, and mechanisms of anxiety suggests new questions about anxiety disorders.
  • Article
    Human social interaction is rarely guided by pure reason. Instead, in situation in which humans have the option to cooperate, to defect, or to punish non-cooperative behavior of another person, they quite uniformly tend to reciprocate “good” deeds, reject unfair proposals, and try to enforce obedience to social rules and norms in non-cooperative individuals (“free-riders”), even if the punishment incurs costs to the punisher. Abundant research using various game theoretical approaches has examined these apparently irrational human behaviors. This article reviews the evolutionary rationale of how such behavior could have been favored by selection. It explores the cognitive mechanisms required to compute possible scenarios of cooperation, defection, and the detection of cheating. Moreover, the article summarizes recent research developments into individual differences in behavior, which suggest that temperament and character as well as between- and within-sex differences in hormonal status influence behavior in social exchange. Finally, we present an overview over studies that have addressed the question of how neuropsychiatric disorders may alter performance in game theoretical paradigms, and propose how empirical approaches into this fascinating field can advance our understanding of human nature.
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    Full-text available
    Like humans engaged in risky activities, group members of some animal societies take turns acting as sentinels. Explanations of the evolution of sentinel behavior have frequently relied on kin selection or reciprocal altruism, but recent models suggest that guarding may be an individual's optimal activity once its stomach is full if no other animal is on guard. This paper provides support for this last explanation by showing that, in groups of meerkats (Suricata suricatta), animals guard from safe sites, and solitary individuals as well as group members spend part of their time on guard. Though individuals seldom take successive guarding bouts, there is no regular rota, and the provision of food increases contributions to guarding and reduces the latency between bouts by the same individual.
  • Article
    Experimental animal studies suggest that early glucocorticoid exposure may have lasting effects on the neurodevelopment of the offspring; animal studies also suggest that this effect may be eliminated by positive postnatal rearing. The relevance of these findings to humans is not known. We prospectively followed 125 mothers and their normally developing children from pregnancy through 17 months postnatal. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infants were assessed at an average age of 17 months with the Bayley Scales of Infant Development, and ratings of infant-mother attachment classification were made from the standard Ainsworth Strange Situation assessment. Prenatal cortisol exposure, indexed by amniotic fluid levels, negatively predicted cognitive ability in the infant, independent of prenatal, obstetric, and socioeconomic factors. This association was moderated by child-mother attachment: in children with an insecure attachment, the correlation was [r(54) = -.47, p < .001]; in contrast, the association was nonexistent in children who had a secure attachment [r(70) = -.05, ns]. These findings mimic experimental animal findings and provide the first direct human evidence that increased cortisol in utero is associated with impaired cognitive development, and that its impact is dependent on the quality of the mother-infant relationship.
  • Article
    Problems with language and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood and adolescence are often strongly linked to low scholastic performance. Early recognition of children who are at increased risk is necessary. Our objective was to determine whether mixed-handedness, which is associated with atypical cerebral laterality, is associated with language, scholastic, and ADHD symptoms in childhood and adolescence. Prospective data come from the Northern Finland Birth Cohort 1986, a longitudinal, population-based birth cohort with assessments when children were 7 to 8 and 16 years of age (N = 7871). Teacher, parent, and/or adolescent reports were used to assess language difficulties, scholastic performance, and mental health, including ADHD symptoms. Mixed-handed children, relative to right-handed, had approximately a twofold increase in odds of having difficulties with language and scholastic performance at the age of 8 years. Eight years later, as 16-year-olds, adolescents had twofold increase in odds concerning difficulties in school with language and with ADHD symptoms. Mixed-handed children were more likely to have scores indicating probable psychiatric disturbance, including ADHD symptoms. As adolescents, mixed-handed children with previous behavioral problems were at considerably higher risk for scoring within the range of probable ADHD-inattention or ADHD-combined case. Mixed-handedness was associated with greater symptom severity in children and adolescents (P = .01) concerning psychiatric disturbance and ADHD inattention but not ADHD hyperactivity. The results indicate that mixed-handed children have a greater likelihood of having language, scholastic, and mental health problems in childhood and that these persist into adolescence. Thus, these results suggest that mixed-handedness, particularly in the presence of difficulties, could aid in the recognition of children who are at risk for stable problems. Additional research is needed to understand the connections between neural substrates related to atypical cerebral asymmetry, mixed-handedness, and mental health problems including ADHD symptoms.
  • Article
    There is extensive evidence in rats that prenatal environmental stress (PES) exposure and early postnatal altered maternal care, as a consequence of stress during gestation, can detrimentally affect the brain and behavioral development of the offspring. In order to separate the effect of PES on the fetuses from that on the behavior of the mother, in the present study, we used a cross-fostering procedure in which PES-fetuses were raised by non-stressed mothers and non PES-fetuses were raised by stressed mothers. In Experiment 1, non-stressed mothers showed significantly more maternal behavior than stressed mothers. In Experiment 2, when the female offspring from Experiment 1 reached maturity, they were tested for: (1) induced maternal behavior (MB), (2) plasma levels of corticosterone (Cpd B), progesterone (P), and estradiol (E2), (3) number of accessory olfactory bulb (AOB) mitral cells, and (4) c-fos expression measured in AOB and medial preoptic area (MPOA) neurons. We replicated our previous findings that the PES group reared by their own stressed mothers, when adult, attacked the young, expressed disorganized MB and showed altered Cpd B, P and E2 levels, plus a male-like neuro-morphological pattern in the AOB, by comparison with the non-PES group, reared by their own non-stressed mothers. By contrast, when adult, the PES group reared by non-stressed mothers showed hormonal and morphological neuronal alterations, but they displayed appropriate (full) MB. The non-PES group raised by stressed mothers also showed altered hormone levels, but showed full MB and no morphological neuronal changes. Significant differences in the AOB and MPOA c-fos activity, related to whether or not MB was expressed, were found in the non-PES groups, but not in the PES group reared by non-stressed mothers.
  • Article
    Exposure to stress during critical periods of an organism's maturation can result in permanent behavioral changes and induced hyper-responsive to aversive stimuli as adult. Hippocampus is a plastic and vulnerable brain structure that is susceptible to damage during aging and repeated stress. The present study examines the effect of maternal restraint stress on the level of GAP-43, pGAP-43 and synaptophysin in the hippocampus of rat pups. Prenatal stress (PS) causes a significant increase of GAP-43 and pGAP-43 (p<or=0.001) in the pup's hippocampus during postnatal days 7 and 14, but not at later ages. Up-regulation of GAP-43 and pGAP-43 may alter the pattern of axonal growth and synapses' formation in the pup's brain since the first two postnatal weeks are correlated with peak period of synaptogenesis in the rat brain. We also examined the level of synaptophysin, a synaptic vesicle membrane protein, in the pup's brain. Our finding revealed that, PS causes a significant decrease of synaptophysin in the pup's hippocampus as compared to control (p<or=0.001). These changes are due to the direct effects of maternal stress hormone since repeated injection with corticosterone (CORT, 40 mg/kg) to pregnant rat during gestation days (GDs) 14-21 also gave the same results. Abnormal axonal sprouting and reorganization together with the alterations in synaptic vesicle membrane protein during the critical period of synaptogenesis may lead to a defect in synapse formation and axonal pruning in the hippocampus. These changes may be associated with stress-induced impairment of hippocampal function that occurs in later life of the offspring.
  • Article
    There are several independent prospective studies showing that a wide variety of forms of prenatal stress can have long-term effects on the behavioural and cognitive outcome for the child. Animal studies have shown that prenatal stress, as well as affecting behaviour, can also reprogram the function of the HPA axis in the offspring. However, the effects on the HPA axis are very variable depending on the nature of the stress, its timing in gestation, the genetic strain of the animal, the sex and age of the offspring and whether basal or stimulated HPA axis responses are studied. There are also several recent studies showing long-term effects of prenatal stress on basal cortisol levels, or cortisol responses to stress, in humans. The designs of these studies differ considerably, many are small, and the effects on outcome are also varied. There is little evidence, so far, that altered function of the HPA axis in the child mediates the behavioural or cognitive alterations observed to be associated with prenatal stress.
  • Article
    It is well established in animal models that the prenatal environment can have a major impact on stress axis function throughout life. These changes can predispose to various metabolic, cardiovascular, and neurobiological pathophysiologies. Emerging evidence indicates that the same programming effects occur in humans. It is now becoming clear that the pathophysiological effects are not confined to the first-generation offspring and that there is transgenerational memory of fetal experience that can extend across multiple generations. The complex mechanisms by which transgenerational transmission of stress responsiveness occur are rapidly becoming a focus of investigation. Understanding these fundamental biological processes will allow for development of intervention strategies that prevent or reverse adverse programming of the stress response.
  • The goal of our study was to characterise the relationships between trait anxiety symptoms of women during their pregnancies and birth outcomes of their offspring using a longitudinal cohort from the Maternal Health Practices and Child Development Project. We used the State-Trait Personality Index anxiety measure that is based on Spielberger's State-Trait Anxiety Inventory to measure self-reported trait anxiety at two gestational assessments (fourth and seventh months, representing the first and second trimesters, respectively) and at a third assessment shortly after delivery (representing the third trimester). Demographic, social, psychological, substance use and medical factors were assessed prenatally, and outcomes of the 763 live, singleton births were determined at delivery. In regression models, trait anxiety at the second and third trimesters predicted lower birthweight and shorter birth length, controlling for confounders. Anxiety reported at the third trimester predicted shortened gestational age, controlling for confounders. At the first and second trimesters, the relationship of birthweight and birth length to maternal trait anxiety was only significant for severe anxiety. Women whose anxiety reached severe levels for at least two trimesters were significantly more likely to deliver offspring of lower birthweight and shorter birth length than those women who reported severe anxiety at none or only one of the trimesters. Additionally, offspring of women who experienced severe anxiety during all three trimesters had shorter mean gestational age than offspring of women who did not report severe anxiety at any trimester. Women who report chronic, severe trait anxiety are at the highest risk of having shorter gestations and delivering smaller babies.
  • Article
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    "Barker's hypothesis" emerged almost 25 years ago from epidemiological studies of birth and death records that revealed a high geographic correlation between rates of infant mortality and certain classes of later adult deaths as well as an association between birthweight and rates of adult death from ischemic heart disease. These observations led to a theory that undernutrition during gestation was an important early origin of adult cardiac and metabolic disorders due to fetal programming that permanently shaped the body's structure, function, and metabolism and contributed to adult disease. This theory stimulated interest in the fetal origins of adult disorders, which expanded and coalesced approximately 5 years ago with the formation of an international society for developmental origins of health and disease (DOHaD). Here we review a few examples of the many emergent themes of the DOHaD approach, including theoretical advances related to predictive adaptive responses of the fetus to a broad range of environmental cues, empirical observations of effects of overnutrition and stress during pregnancy on outcomes in childhood and adulthood, and potential epigenetic mechanisms that may underlie these observations and theory. Next, we discuss the relevance of the DOHaD approach to reproductive medicine. Finally, we consider the next steps that might be taken to apply, evaluate, and extend the DOHaD approach.
  • Article
    Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (+/-0.83), 25 (+/-0.9) and 31 (+/-0.9) weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel-based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.
  • Article
    Although postnatal psychologic distress has been widely studied for many years, particularly with a focus on postpartum depression, symptoms of maternal depression, stress, and anxiety are not more common or severe after childbirth than during pregnancy. This paper reviews the newer body of research aimed at identifying the effects of women's antenatal psychologic distress on fetal behavior and child development, and the biologic pathways for this influence. These studies are in line with the growing body of literature supporting the "fetal origins hypothesis" that prenatal environmental exposures--including maternal psychologic state-based alterations in in utero physiology--can have sustained effects across the lifespan.
  • Article
    Full-text available
    The aim of the present study was to examine the association between prenatal psychosocial stress exposure and subsequent prefrontal cortex-dependent working memory performance in human adults. Working memory performance was assessed using an item-recognition task under 10 mg hydrocortisone (cortisol) and placebo conditions in a sample of 32 healthy young women (mean age = 25 +/- 4.34 years) whose mothers experienced a major negative life event during their pregnancy (Prenatal Stress, PS group), and in a comparison group of 27 healthy young women (mean age = 24 +/- 3.4 years). The two groups did not differ in the placebo condition, however, subjects in the PS group showed longer reaction times after hydrocortisone administration compared with subjects in the comparison group (p = .02). These findings provide support for an association between prenatal stress exposure and the potential modulatory effect of cortisol on working memory performance in young adults, which may reflect compromised development of the prefrontal cortex in prenatal life.
  • Article
    Maternal stress and anxiety during pregnancy are related to negative developmental outcomes for offspring, both physiological and psychological, from the fetal period through early adolescence. This robust relationship is likely to be partly explained by alterations in fetal neurodevelopmental programming, calling for further examination of neurophysiologically-based cognitive markers that may be related to the altered structure-function relationships that contribute to these negative developmental outcomes. The current investigation examined the relationship between perinatal maternal anxiety and neonatal auditory evoked responses (AERs) to mother and stranger voices. Results indicated that neonates of low-anxiety mothers displayed more negative frontal slow wave amplitudes in response to their mother's voice compared to a female stranger's voice, while neonates of high-anxiety mothers showed the opposite pattern. These findings suggest that neonates of perinatally anxious mothers may demonstrate neurophysiologically-based differences in attentional allocation. This could represent one pathway to the negative psychological outcomes seen throughout development in offspring of anxious mothers.
  • Article
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    Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.
  • Article
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    Recent human studies have shown that a wide variety of prenatal stressors, from anxiety and partner relationship problems, to natural disasters, increase the risk for a diverse range of adverse neurodevelopmental outcomes in the child. These include impaired cognitive development and behavioral problems, autism and schizophrenia. However, many questions remain about the underlying processes. Much of the research, based on animal studies, has focussed on the maternal HPA axis, with mixed results. Maternal stress or anxiety during pregnancy has been found to be weakly associated with raised maternal cortisol, if at all. The placenta may be a more promising programming vector, because it controls fetal exposure to the maternal environment. Animal studies indicate that prenatal stress can affect the activity of the placental barrier enzyme 11-betaHSD2, which metabolises cortisol. We review the evidence for a similar mechanism in humans and how maternal stress may cause other changes in the placenta which affect fetal neurodevelopment.
  • Article
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    Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring. A 'prenatal cross-fostering' design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother-child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother-offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother-offspring pairs and therefore was attributable to inherited factors. Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects.
  • Article
    To assess the association between maternal anxiety during pregnancy and the brain activity of 17 year old adolescents performing two cognitive control tasks. Twenty-three 17 year old boys of mothers whose level of anxiety was measured during pregnancy were investigated using ERP while performing a Go/Nogo paradigm assessing exogenous cognitive control and a Gambling paradigm requiring endogenous cognitive control. No effects of antenatal maternal anxiety were observed in the Go/Nogo paradigm. However, in the Gambling paradigm adolescents of the high anxiety group (n=8) showed a less efficient pattern of decision making compared to the adolescents in the low-average anxiety group (n=15). Moreover, only for this task the ERP data showed an enlarged early frontal P2a component in the high anxiety group. The brain activity of adolescents during an endogenous cognitive control task is associated to the level of anxiety experienced by their mother during pregnancy. This association was not observed during an exogenous cognitive control task. This study indicates that a child's brain functionality is related to its mother's anxiety during pregnancy. Endogenous cognitive control is regarded the cognitive function most affected by the level of antenatal maternal anxiety.
  • Article
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    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making.
  • Article
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    Dermatoglyphic asymmetry of fingertip ridge counts is more frequent in schizophrenia patients than normal controls, and may reflect disruptions in fetal development during Weeks 14-22 when fingerprints develop. However, there are no data in humans linking specific adverse events at specific times to dermatoglyphic asymmetries. Our objective was to determine whether prenatal exposure to a natural disaster (1998 Quebec ice storm) during Weeks 14-22 would result in increased dermatoglyphic asymmetry in children, and to determine the roles of maternal objective stress exposure, subjective stress reaction, and postdisaster cortisol. Ridge counts for homologous fingers were scored for 77 children (20 target exposed [Weeks 14-22] and 57 nontarget exposed [exposed during other gestation weeks]). Children in the target group had more than 0.50 SD greater asymmetry than the nontarget group. Within the target group, children whose mothers had high subjective ice storm stress had significantly greater asymmetry than those with lower stress mothers, and maternal postdisaster cortisol had a significant negative correlation with the children's dermatoglyphic asymmetry (r = -.56). Prenatal maternal stress during the period of fingerprint development results in greater dermatoglyphic asymmetry in their children, especially in the face of greater maternal distress.
  • Article
    Prenatal stress has been linked to several adverse neurobehavioral outcomes, which may share a common pathophysiology with autism. We aimed to examine whether prenatal stress exposure after maternal bereavement is associated with an increased risk of autism later in life. We conducted a nationwide population-based cohort study of all 1492709 singletons in Denmark born from 1978 to 2003. A total of 37275 children were born to women who lost a close relative during pregnancy or up to 1 year before pregnancy. These children were included in the exposed group, and the remaining children were in the unexposed group. All children were followed up from birth until their death, migration, onset of autism, or the end of 2006. Information on autism was obtained from the Danish Psychiatric Central Register. We used Cox regression models to estimate hazard ratios in the exposed group compared with those in the unexposed group. Maternal bereavement during the prenatal period was not associated with an increased risk of autism in the offspring. The hazard ratios did not differ by the nature of the exposure (maternal relationship to the deceased or cause of death). The hazard ratios were comparable between the 5 prenatal exposure periods under study (7-12 months before pregnancy, 0-6 months before pregnancy, first trimester, second trimester, and third trimester). This is the first population-based cohort study to examine the effect of prenatal stress on autism in childhood. Our data do not support any strong association between prenatal stress after maternal bereavement and the risk of autism.
  • Article
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    Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
  • Article
    The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birth weight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects.
  • Article
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    Emotions research is now routinely grounded in evolution, but explicit evolutionary analyses of emotions remain rare. This article considers the implications of natural selection for several classic questions about emotions and emotional disorders. Emotions are special modes of operation shaped by natural selection. They adjust multiple response parameters in ways that have increased fitness in adaptively challenging situations that recurred over the course of evolution. They are valenced because selection shapes special processes for situations that have influenced fitness in the past. In situations that decrease fitness, negative emotions are useful and positive emotions are harmful. Selection has partially differentiated subtypes of emotions from generic precursor states to deal with specialized situations. This has resulted in untidy emotions that blur into each other on dozens of dimensions, rendering the quest for simple categorically distinct emotions futile. Selection has shaped flexible mechanisms that control the expression of emotions on the basis of an individual's appraisal of the meaning of events for his or her ability to reach personal goals. The prevalence of emotional disorders can be attributed to several evolutionary factors.
  • Article
    Sex differences are found in animal studies concerning the relationship between prenatal maternal stress and outcome of the offspring. Most human studies in this field have not addressed sex differences, although differences between boys and girls may elucidate the biochemical as well as psychological processes involved. Associations between prenatal maternal emotional complaints and behavioural problems of toddlers and preschoolers as assessed by both mothers and fathers are studied separately for boys and girls. Healthy Dutch Caucasian singleton, pregnant women (N=444) answered questionnaires about anxiety and depression in every trimester of pregnancy. When their children (227 boys, 217 girls) were between 14 and 54 months old, both parents reported on their current feelings of depression and anxiety and on the behavioural problems of their children. Prenatal maternal emotional complaints were found to be associated with child behavioural problems both in boys and in girls, but in different ways. Prenatal maternal emotional complaints during the first trimester were associated with total and internalizing behavioural problems for boys. Emotional complaints during the third trimester were associated with total, internalizing, as well as externalizing behavioural problems for girls. Differentiation according to sex and information on timing of emotional complaints during pregnancy is needed in studies concerning the relation between prenatal maternal emotional complaints and child outcome.
  • Article
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    The current study sought to determine whether prenatal 3,4-methylenedioxy-N-methamphetamine (MDMA) exposure from E14-20 in the rat resulted in behavioral sequelae in adult offspring. Prenatal MDMA exposure results in increased dopaminergic fiber density in the prefrontal cortex, striatum and nucleus accumbens of young rats. Since these areas are critical in response to novelty, reward, attention and locomotor activity, we hypothesized that prenatal MDMA exposure would produce significant changes in the performance of tasks that examine such behaviors in adult rats. Adult rats prenatally exposed to MDMA exhibited greater activity and spent more time in the center during a novel open field test as compared to controls. This increased activity was not reflected in normal home cage activity. Prenatal exposure to MDMA did not affect feeding or food reward. It did not alter cocaine self-administration behaviors, nor did it have an effect on the locomotor response to amphetamine challenge. Finally, while prenatal MDMA did not affect performance in the radial arm maze or the Morris water maze (MWM), these animals demonstrated altered performance in a cued MWM paradigm. Prenatal MDMA exposure resulted in perseverative attendance to a hanging cue when the platform in the MWM was removed as compared to controls. Together, these data demonstrate that prenatal exposure to MDMA results in a behavioral phenotype in adult rats characterized by reduced anxiety, a heightened response to novelty, and "hyperattentiveness" to environmental cues during spatial learning.
  • Article
    Epidemiological studies have reported associations between measures of size and weight at birth and disease risk in later life. Alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to prenatal stress has been proposed as one underlying mechanism. The present study investigated in humans the association of prenatal psychosocial stress exposure with subsequent HPA axis regulation in adult life, with a focus on measures of response to challenge and feedback sensitivity. Healthy young adults whose mothers experienced severe stress during their pregnancy in form of major negative life events (e.g. death of someone close; prenatal stress (PS) group, n=31) and an age-matched comparison group (CG, n=30) underwent the Trier Social Stress Test (TSST) and a 1 microg ACTH(1-24) stimulation test. In addition, a diurnal cortisol profile was assessed. ACTH concentrations following a standardized behavioural challenge paradigm (TSST) were marginally significantly higher in PS subjects than in CG subjects (p=.06). Pre-TSST adrenocortical (cortisol) levels were lower (p=.007), whereas the increase in cortisol in response to the TSST was higher (p=.03) in PS subjects compared to CG subjects. Cortisol concentrations following a pharmacological stimulation test simulating pituitary activity (ACTH(1-24) test) were significantly lower in PS than in CG subjects (p=.006). No differences emerged between the two groups in basal diurnal cortisol levels. This study provides first evidence in humans of an association between prenatal psychosocial stress exposure and subsequent alterations in the regulation of the HPA axis.
  • Article
    Animal studies have shown that prenatal stress has persisting effects on several aspects of offspring development; more recent studies show that this effect may be eliminated by positive postnatal rearing. Human studies of prenatal anxiety/stress are now also beginning to document links between antenatal stress/anxiety and behavioural and cognitive development of the child; however, there is no human evidence as to whether the early caregiving environment moderates the effect of antenatal anxiety/stress on child outcomes. Antenatal and postnatal measures of stress were collected on 123 women who were recruited from an antenatal clinic. Laboratory-based assessment of the children's cognitive development and fearfulness were assessed when the children were aged 17 months. In addition, child-parent attachment quality was assessed using the Strange Situation. Attachment classification moderated the link between antenatal stress and observed fearfulness. The effect of antenatal stress on fearfulness was most accentuated in children with an Insecure/Resistant attachment classification; the significant antenatal stress x attachment classification interaction held after controlling for postnatal stress and obstetric, social and demographic factors. Attachment did not moderate the effects of antenatal anxiety on cognitive development. These findings provide the first human evidence that postnatal parenting may moderate the adverse effects of antenatal stress. These results raise developmental questions about the timing and effect of interventions to reduce the adverse effects of antenatal stress exposure.
  • Article
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    Postpartum depression (PPD) is considered a major public health problem that conveys risk to mothers and offspring. Yet PPD typically occurs in the context of a lifelong episodic illness, and its putative effects might derive from the child's exposure to other episodes, in pregnancy or later childhood. The aim of the study is to test two hypotheses: (1) that the effects of PPD on adolescent outcomes are partly explained by antepartum depression (APD) and (2) that the effects of APD and PPD are both explained by later exposure to the mother's depression. A random sample of 178 antenatal patients was drawn from two general medical practices in South London; 171 gave birth to live infants, and 150 (88%) were assessed at 3 months post partum, with 121 of their offspring (81%) assessed for emotional disorders (ED), disruptive behaviour disorders (DBD) and IQ, at 11 and 16 years of age. When APD and subsequent episodes of depression were taken into account, PPD had a significant effect on adolescent IQ, especially for boys, but did not predict psychopathology. ED and DBD in adolescence were predicted by the extent of exposure to maternal depression after 3 months post partum; a significant effect of APD on ED in girls was accounted for by later exposure to the mother's illness. Mothers' symptoms of anxiety, smoking and alcohol use in pregnancy did not predict adolescent outcomes, once maternal depression was taken into account. Some effects attributed to mothers' mental health problems in pregnancy or post partum may be mediated by cumulative exposure to maternal illness, probably reflecting genetic influence and gene-environment correlation. However, PPD has a direct effect on cognition. Clinicians should endeavour to identify women with depression in pregnancy (31% of this sample) and help them to manage their lifelong illness.
  • Prenatal maternal stress (PNMS) has been linked with adverse health outcomes in the offspring through experimental studies using animal models and epidemiological studies of human populations. The purpose of this review article is to establish a parallel between animal and human studies, while focusing on methodological issues and gaps in knowledge. The review examines the quality of recent evidence for prevailing PNMS theoretical models, namely the biopsychosocial model for adverse pregnancy outcomes and the fetal programming model for chronic diseases. The investigators used PubMed (2000-06) to identify recently published original articles in the English language literature. A total of 103 (60 human and 43 animal) studies were examined. Most human studies originated from developed countries, thus limiting generalisability to developing nations. Most animal studies were conducted on non-primates, rendering extrapolation of findings to pregnant women less straightforward. PNMS definition and measurement were heterogeneous across studies examining similar research questions, thus precluding the conduct of meta-analyses. In human studies, physical health outcomes were often restricted to birth complications while mental health outcomes included postnatal developmental disorders and psychiatric conditions in children, adolescents and adults. Diverse health outcomes were considered in animal studies, some being useful models for depression, schizophrenia or attention deficit hyperactivity disorder in human populations. The overall evidence is consistent with independent effects of PNMS on perinatal and postnatal outcomes. Intervention studies and large population-based cohort studies combining repeated multi-dimensional and standardised PNMS measurements with biomarkers of stress are needed to further understand PNMS aetiology and pathophysiology in human populations.
  • Article
    Prenatal stress is associated with an increased vulnerability to neurodevelopmental disorders, including autism and schizophrenia. To determine the critical time window when fetal antecedents may induce a disease predisposition, we examined behavioral responses in offspring exposed to stress during early, mid, and late gestation. We found that male offspring exposed to stress early in gestation displayed maladaptive behavioral stress responsivity, anhedonia, and an increased sensitivity to selective serotonin reuptake inhibitor treatment. Long-term alterations in central corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, as well as increased hypothalamic-pituitary-adrenal (HPA) axis responsivity, were present in these mice and likely contributed to an elevated stress sensitivity. Changes in CRF and GR gene methylation correlated with altered gene expression, providing important evidence of epigenetic programming during early prenatal stress. In addition, we found the core mechanism underlying male vulnerability may involve sex-specific placenta responsivity, where stress early in pregnancy significantly increased expression of PPARalpha (peroxisome proliferator-activated receptor alpha), IGFBP-1 (insulin-like growth factor binding protein 1), HIF3alpha (hypoxia-inducible factor 3a), and GLUT4 (glucose transporter 4) in male placentas but not females. Examination of placental epigenetic machinery revealed basal sex differences, providing further evidence that sex-specific programming begins very early in pregnancy, and may contribute to the timing and vulnerability of the developing fetus to maternal perturbations. Overall, these results indicate that stress experience early in pregnancy may contribute to male neurodevelopmental disorders through impacts on placental function and fetal development.
  • This was a prospective study designed to determine the extent to which the degree of exposure to prenatal maternal stress due to a natural disaster explains variance in the intellectual and language performance of offspring at age 5(1/2) while controlling for several potential confounding variables. Subjects were eighty-nine 5(1/2)-year-old children whose mothers were pregnant during a natural disaster: the January 1998 ice storm crisis in the Canadian province of Québec that resulted in power losses for 3 million people for as long as 40 days. In June 1998, women completed several questionnaires including those about the extent of objective stress (Storm 32) and subjective distress (Impact of Events Scale-Revised) experienced due to the storm. Their children were assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised (IQ) and Peabody Picture Vocabulary Test-Revised (language) at 5(1/2) years of age, and mothers completed assessments of recent life events and psychological functioning. Children exposed in utero to high levels of objective stress had lower Full Scale IQs, Verbal IQs, and language abilities compared to children exposed to low or moderate levels of objective prenatal maternal stress; there were no effects of subjective stress or objective stress on Performance IQs. Trend analyses show that for all outcome variables except Block Design, there was a significant curvilinear association between objective stress and functioning. Prenatal exposure to a moderately severe natural disaster is associated with lower cognitive and language abilities at 5(1/2) years of age.
  • Article
    Sexually dimorphic rough-and-tumble play patterns were compared in male and female rats derived from control mothers and mothers stressed from days 14-21 of pregnancy. Animals were weaned into groups of 8 consisting of 2 males and 2 females from each treatment. Play in the home cage was recorded at 25, 28, 31, 34, 37 and 45 days of age and was most intense on day 31. The overall level of play was significantly higher in control males than in females or stressed males. Control males showed higher levels of the pinning component of rough-and-tumble play than females or stressed males. No play partner preferences were detected in any group. In adulthood, a higher percentage of stressed than control males displayed the female lordotic pattern. No deficits in ejaculatory behavior occurred in the stressed males. Since maternal stress alters patterns of plasma testosterone in male fetuses, the data suggest that the sexual differentiation of social play begins during prenatal ontogeny in the rat. The present results show that sexually dimorphic behaviors displayed before puberty are incompletely masculinized in prenatally stressed males, a finding similar to that reported for a number of adult behaviors.
  • Article
    This study compared hyperactive and normal girls and boys on their mother-child interactions, family psychiatric status and ratings on the Personality Inventory for Children (PIC). Hyperactive children were less compliant and more negative, and their mothers responded more negatively to their compliance than mothers of normal children. Mothers of hyperactive children reported more depression, marital discord and psychiatric problems in their relatives, and rated their children more deviant on 15 of 16 PIC scales than normal children. Hyperactive boys received more direction and praise, and had greater maternal concern about their adjustment than hyperactive girls or normal children.