Prenatal Developmental Origins of Future Psychopathology: Mechanisms and Pathways

In the paper

“Human studies relate maternal prenatal distress and maternal HPA activation to an increased risk for autism spectrum disorder (ASD), schizophrenia, depression, anxiety, and ADHD in offspring (Chan et al. 2018).”

What the sources say

• Not checked yetcites Chan et al. 2018

In the paper

“Results were similar for prenatal depression and included potential confounders (i.e., maternal postnatal anxiety and depression, socioeconomic factors, obstetrical risks, and maternal parenting) in the statistical models.”

What the sources say

• Not checked yetcites O’Donnell et al. 2014

In the paper

“Exposure to these more ecologically valid social stressors early in gestation often results in pregnancy loss, whereas later exposure appears to have long-lasting cognitive, neurological, and behavioral effects in offspring, including hyperresponsiveness to stress and increased anxiety (Brunton 2013).”

What the sources say

• Not checked yetcites Brunton 2013

In the paper

“PS exposure affects stress neurocircuitry in mice, including increasing corticotropin-releasing factor in the amygdala and reducing hippocampal glucocorticoid receptor expression (Mueller & Bale 2008).”

What the sources say

• Not checked yetcites Mueller & Bale 2008

In the paper

“a Danish study that included 10,000 children with autism found associations between maternal viral infection during the first trimester and maternal bacterial infection during the second trimester and ASD risk in children (Atladóttir et al. 2010).”

What the sources say

• Not checked yetcites Atladóttir et al. 2010

In the paper

“A recent prospective longitudinal study documented that both prenatal maternal depression and cortisol levels during the first and second trimesters were related to emotional reactivity in preschool-age offspring, suggesting that both of these prenatal exposures may have independent, sex-specific effects (Swales et al. 2018).”

What the sources say

• Not checked yetcites Swales et al. 2018

In the paper

“An offspring’s sex appears to play a critical role in determining outcomes and, further complicating matters, interacts with the timing and type of PS exposure (Brunton & Russell 2010).”

What the sources say

• Not checked yetcites Brunton & Russell 2010

In the paper

“Since prenatal maternal distress may be associated with alterations in HPA axis regulation and higher levels of circulating glucocorticoids—which can affect placenta functioning and cross the placenta and reach the fetus (Monk et al. 2016, Stirrat et al. 2018)”

What the sources say

• Not checked yetcites Monk et al. 2016
• Not checked yetcites Stirrat et al. 2018

In the paper

“maternal socioeconomic adversity has been associated with lower levels of placental HSD11B2 methylation, with greater effects in males than females (Appleton et al. 2013).”

What the sources say

• Not checked yetcites Appleton et al. 2013

In the paper

“The hypothalamic–pituitary–adrenal (HPA) axis is a central component of the hormonal stress response system. It is responsible for secreting glucocorticoids, including cortisol, which alerts the organism to potential threat and maintains homeostasis (Herman & Cullinan 1997).”

What the sources say

• Not checked yetcites Herman & Cullinan 1997

In the paper

“MIA [indexed via levels of interleukin-6 (IL-6) and C-reactive protein] is related to potentially important intermediate phenotypes in the fetus and infant: decreased fetal heart rate variability (considered a physiological substrate of emotion regulation), alterations in functional connectivity between the medial prefrontal cortex and temporoparietal junction, and larger right amygdala volume and”

What the sources say

• Not checked yetcites Rudolph et al. 2018
• Not checked yetcites Spann et al. 2018

In the paper

“Overall, animal studies suggest that prenatal stress (PS for animal models) results in elevated levels of basal and reactivity (i.e., poststressor) corticosteroids and decreased negative feedback of the HPA axis (Maccari et al. 1995).”

What the sources say

• Not checked yetcites Maccari et al. 1995

In the paper

“Environmental insults can alter placental biology, in part via epigenetic modifications, and lead to perturbation of the transport and waste removal functions, such as a deficiency in nutrient transport leading to altered fetal growth (Angiolini et al. 2006).”

What the sources say

• Not checked yetcites Angiolini et al. 2006

In the paper

“These changes have been documented in rats alongside increased cognitive problems in offspring, anxiety, and depression-like behaviors, even through adulthood (Brunton & Russell 2010, St-Cyr et al. 2017).”

What the sources say

• Not checked yetcites Brunton & Russell 2010
• Not checked yetcites St-Cyr et al. 2017

In the paper

“maternal cytokines can impact the fetus by (a) crossing the placenta and entering the fetal compartment (see the section titled Placental Functioning: DNA Modification), (b) affecting the placenta itself and causing placental inflammation and associated cytokine production, (c) creating fetal immune dysregulation, or (d) a combination of the three (Meltzer & Van de Water 2016).”

What the sources say

• Not checked yetcites Meltzer & Van de Water 2016

In the paper

“In many studies, male offspring appear to be the most strongly affected. Interestingly, they often present with what is known as a dysmasculinized phenotype (i.e., with behaviors and gene expression patterns most commonly seen in females) (Bale 2016).”

What the sources say

• Not checked yetcites Bale 2016 source

In the paper

“one study of 116 women with elevated cortisol levels during the second and third trimesters found increased stress responses in newborns but did not find an association between maternal distress and cortisol (Davis et al. 2011)”

What the sources say

• Not checked yetcites Davis et al. 2011

In the paper

“Because cytokines are known to be involved in dendritic growth and neuronal survival and differentiation (Marx et al. 2001), MIA may exert its effect on offspring’s outcomes through multiple aspects of brain development”

What the sources say

• Not checked yetcites Marx et al. 2001

In the paper

“maternal stress was associated with increased placental DNA methylation of HSD11B2, which, in turn, was associated with a reduction in fetal coupling, indicative of delayed neurobehavioral development (N = 61, 51% female) (Monk et al. 2016).”

What the sources say

• Not checked yetcites Monk et al. 2016

In the paper

“None of these papers identified sex effects in infant outcomes.”

In the paper

“Placental DNA methylation of these two genes predicted poorer self-regulation, lower muscle tone, and more lethargy in neonates (N = 482, 47% female) (Conradt et al. 2013).”

What the sources say

• Not checked yetcites Conradt et al. 2013

In the paper

“it is likely that maternal distress affects the development of the offspring’s HPA circuitry and brain development, as well as the subsequent risk for psychopathology.”

In the paper

“Given the array of disorders that have been associated with maternal perinatal inflammation, is it likely that the specific cause of inflammation (i.e., in response to bacterial infection versus experienced stress), the timing of exposure, and other environmental and individual factors (e.g., the offspring’s sex, genetic risk for a specific disease) interact and result in different processes”

In the paper

“This critical period, also subserving corticogenesis, is characterized by considerable plasticity and, thus, vulnerability, yet also opportunity (Scheinost et al. 2017, Werker & Hensch 2015).”

What the sources say

• Not checked yetcites Scheinost et al. 2017
• Not checked yetcites Werker & Hensch 2015

In the paper

“In one provocative paper, concordance between maternal prenatal (at 25 gestational weeks) and postpartum depression versus nonconcordance (so, two hits of depression versus only one in a traditional diathesis model) was associated with superior scores on the Bayley Scales of Infant and Toddler Development at 3, 6, and 12 months (Sandman et al. 2012).”

What the sources say

• Not checked yetcites Sandman et al. 2012

In the paper

“Barker (1995) describes the fetus as adapting to his or her environment with changes in their biology that become programmed, meaning embedded and long-lasting, with the idea that these programmed changes potentially put the offspring at risk for future disease.”

What the sources say

• Not checked yetcites Barker 1995

In the paper

“Thus, it is likely that the type of infectious agent and timing of maternal inflammation interact with an offspring’s sex and possibly underlie some of the inconsistency in findings (Rana et al. 2012).”

What the sources say

• Not checked yetcites Rana et al. 2012

In the paper

“Glover (2011) and Sandman et al. (2013) suggest that fetal adaptations are aimed at ensuring survival and that exposure to maternal prenatal distress functions as a communication foreshadowing characteristics of the postnatal world for which the fetus can begin to prepare via biological adaptations.”

What the sources say

• Not checked yetcites Glover 2011
• Not checked yetcites Sandman et al. 2013

In the paper

“The direction of findings has also varied, with some studies documenting blunted HPA axis and stress responses in offspring (Vedhara et al. 2012) and others documenting the opposite (Capron et al. 2015).”

What the sources say

• Not checked yetcites Vedhara et al. 2012
• Not checked yetcites Capron et al. 2015

In the paper

“At the midpoint of gestation, 20 weeks, the end of the early fetal period, the brain has the necessary structures for mature functioning, albeit with a smooth, lissencephalic versus ridged cortical plate, as the ridges (gyri) and depressions (sulci) are just beginning to form (Encha-Razavi & Sonigo 2003, Fogliarini et al. 2005).”

What the sources say

• Not checked yetcites Encha-Razavi & Sonigo 2003
• Not checked yetcites Fogliarini et al. 2005

In the paper

“a viral challenge with polyinosinic:polycytidylic acid on GD9 resulted in hindered spatial exploration in offspring, whereas the same exposure on GD17 led to poorer performance on a discrimination reversal learning task (i.e., increased perseverative behavior) (Meyer et al. 2006).”

What the sources say

• Not checked yetcites Meyer et al. 2006

In the paper

“a significant association between maternal prenatal depression and risk for depression at 18 years old in females but not males (Quarini et al. 2015).”

What the sources say

• Not checked yetcites Quarini et al. 2015

In the paper

“some studies show that males are more likely to be affected and have a 72% increased risk of developing childhood attention-deficit/hyperactivity disorder (ADHD) if their mother lost a spouse or child during pregnancy (van den Bergh et al. 2017)”

What the sources say

• Not checked yetcites van den Bergh et al. 2017

In the paper

“Finally, a newer premise in the DOHaD model is that adaptation itself is being programmed prenatally. Here, exposure to prenatal distress fosters offspring’s sensitivity to the environmental context, which is viewed as a risk or opportunity factor, depending on the qualities of the child’s life (Hartman et al. 2018).”

What the sources say

• Not checked yetcites Hartman et al. 2018

In the paper

“Alternatively, prenatal adaptations are hypothesized as inherently coming at a cost—that is, a short-term survival benefit associated with future risk for poor neurodevelopmental outcomes.”

In the paper

“high maternal prenatal anxiety related to greater likelihood of ADHD in 4-year-old males and emotion regulation problems in females (O’Donnell et al. 2014).”

What the sources say

• Not checked yetcites O’Donnell et al. 2014

In the paper

“In a preclinical study, PS induced in rats was associated with depression-like behavior and with a reduction of PGC-1α protein (a regulator of mitochondrial biogenesis) in the frontal cortex and hippocampus of their 3-month-old male offspring (Glombik et al. 2015).”

What the sources say

• Not checked yetcites Glombik et al. 2015

In the paper

“Myelin, which is first detected at between 20 and 28 weeks, enhances the speed and accuracy of neuronal communication (Tau & Peterson 2010).”

What the sources say

• Not checked yetcites Tau & Peterson 2010

In the paper

“The vast majority of this work has examined infection-related MIA, and as in the rodent literature, findings vary depending on the timing of inflammation and type of infectious agent (Careaga et al. 2017).”

What the sources say

• Not checked yetcites Careaga et al. 2017

In the paper

“administering bacterial versus viral insults at the same time (GD 9) in males results in, respectively, brain and behavioral differences associated with schizophrenia [i.e., enlarged ventricles and reduced prepulse inhibition in males (Li et al. 2009)] or increases in anxiety and depression-like behaviors (Depino 2018).”

What the sources say

• Not checked yetcites Li et al. 2009
• Not checked yetcites Depino 2018

In the paper

“Maternal sleep patterns undergo changes throughout pregnancy due to alterations in reproductive hormones, increased nocturia, and body aches (Pien & Schwab 2004).”

What the sources say

• Not checked yetcites Pien & Schwab 2004

In the paper

“MSD has been found to impair hippocampal neurogenesis (Zhao et al. 2015) and synaptic plasticity (Yu et al. 2018), which have been causally linked to disruptions in emotional and cognitive functioning.”

What the sources say

• Not checked yetcites Zhao et al. 2015
• Not checked yetcites Yu et al. 2018

In the paper

“Early in pregnancy, deficits in maternal nutrient intake have been shown to affect cell proliferation, while deficits later in pregnancy have been shown in preclinical studies to affect cell differentiation, synaptogenesis, and dendritic arborization (Monk et al. 2013, Prado & Dewey 2014).”

What the sources say

• Not checked yetcites Monk et al. 2013
• Not checked yetcites Prado & Dewey 2014

In the paper

“Based on a nonnutritive sucking paradigm, 3-day-old infants showed they identified their mother’s voice (reading Dr. Seuss) over another woman’s and sucked more to elicit hearing it (DeCasper & Fifer 1980).”

What the sources say

• Not checked yetcites DeCasper & Fifer 1980

In the paper

“Before birth, fetuses register sensory experience, and there is evidence of transnatal learning—that is, learning that occurs as a fetus is carried across the birth divide (Busnel et al. 2017, Moon & Fifer 2000).”

What the sources say

• Not checked yetcites Busnel et al. 2017
• Not checked yetcites Moon & Fifer 2000

In the paper

“Because the developing brain exerts a high metabolic demand, microbial colonization may significantly influence brain maturation and, potentially, the risk for neuropsychiatric disease (Keunen et al. 2014).”

What the sources say

• Not checked yetcites Keunen et al. 2014

In the paper

“Finally, because poor prenatal sleep is related to elevations in both maternal circulating cytokines (Okun et al. 2009) and cortisol levels (Bleker et al. 2017),”

What the sources say

• Not checked yetcites Okun et al. 2009
• Not checked yetcites Bleker et al. 2017

In the paper

“this preference for the maternal voice over another woman’s likely subserves bonding while transnatal memory for language-specific properties may undergird language development.”

What the sources say

• Not checked yetcites Busnel et al. 2017
• Not checked yetcites DeCasper & Fifer 1980

In the paper

“Rodent models have typically examined a gestational period comparable to third-trimester human MSD (Radhakrishnan et al. 2015, Yu et al. 2018, Zhao et al. 2015), and the studies examining first- and second-trimester MSD have been inconsistent in documenting emotional deficits (Calegare et al. 2010).”

What the sources say

• Not checked yetcites Radhakrishnan et al. 2015
• Not checked yetcites Yu et al. 2018
• Not checked yetcites Zhao et al. 2015

In the paper

“Because childhood sleep problems are predictive of future psychopathology (Gregory & O’Connor 2002), it is possible that poor maternal prenatal sleep increases offspring’s risk of mental illness through this pathway.”

What the sources say

• Not checked yetcites Gregory & O’Connor 2002

In the paper

“These reductions were more pronounced in male offspring, suggesting increased susceptibility to metabolic programing of the developing brain in males (Jašarević et al. 2015),”

What the sources say

• Not checked yetcites Jašarević et al. 2015

In the paper

“Given emerging fetal imaging studies demonstrating sensory-driven plasticity (Anderson & Thomason 2013), these findings suggest the possibility of in utero shaping of fetal neural organization and infant postnatal behavior based on the pairing of varying maternal emotions”

What the sources say

• Not checked yetcites Anderson & Thomason 2013
• Not checked yetcites Tallet et al. 2016

In the paper

“For example, infants born via vaginal delivery show a bacterial composition resembling their mothers’ vaginal microbiome, whereas babies born via Cesarean section show more skin-like microbiomes (Dominguez-Bello et al. 2010).”

What the sources say

• Not checked yetcites Dominguez-Bello et al. 2010

In the paper

“Altered sleep is a common occurrence, yet any further sleep loss—including that associated with maternal distress—can place both mother and offspring at risk for negative health trajectories, including poor birth outcomes (reviewed elsewhere, see Palagini et al. 2014).”

What the sources say

• Not checked yetcites Palagini et al. 2014

In the paper

“Moreover, recent rodent studies challenge the existence of a sterile in utero environment, suggesting an even earlier mother–infant microbiome transmission, likely through the placental barrier or fetal ingestion of amniotic fluid (Walker et al. 2017).”

What the sources say

• Not checked yetcites Walker et al. 2017

In the paper

“Both maternal experiences of stress and inadequate nutrition may affect the fetus via related biological pathways (Monk et al. 2013).”

What the sources say

• Not checked yetcites Monk et al. 2013

In the paper

“In humans, maternal consumption of a high-fat diet during pregnancy has been associated with an increased incidence of behavioral problems, poorer regulatory capacity, and lower surgency (i.e., low interest and motivation) in infants and children (Gustafsson et al. 2015, Pina-Camacho et al. 2015, Steenweg-de Graaff et al. 2014).”

What the sources say

• Not checked yetcites Gustafsson et al. 2015
• Not checked yetcites Pina-Camacho et al. 2015
• Not checked yetcites Steenweg-de Graaff et al. 2014

In the paper

“This is especially important given the likelihood that distress during pregnancy is highly predictive of postpartum distress and future parenting (Glover & Capron 2017).”

What the sources say

• Not checked yetcites Glover & Capron 2017

In the paper

“Maternal prenatal distress is only one of many, many influences on children’s futures; distress during pregnancy is typically a modifiable factor, and interventions with distressed pregnant women can help women and may positively affect their children as well.”

In the paper

“research into prenatal distress must be considered in context such that prenatal programming via maternal distress occurs as one of a multitude of factors influencing fetal and infant neural organization and brain–behavior development.”

In the paper

“There is no doubt that women feel immense pressure regarding the mothering role (Howorth 2017);”

What the sources say

• Not checked yetcites Howorth 2017

In the paper

“The identification of maternal distress as a factor in prenatal programming, with implications for future neurobehavioral development of the child, introduces a possible time point for providing preventative interventions targeting fetal and child adaptations that may signal risk,”

In the paper

“As indicated, maternal distress may serve as a marker for another variable that is the true agent affecting offspring’s outcome, for example, poor nutrition.”

In the paper

“Indeed, the best rodent models of PS cross-foster the pups during rearing because previously stressed dams parent differently (and/or their PS-exposed offspring elicit different caregiving) (Weinstock 2017), and these models still identify PS effects on offspring’s outcomes.”

What the sources say

• Not checked yetcites Weinstock 2017

In the paper

“For example, prenatal SSRI exposure is associated with gray matter expansion in the amygdala and insula in sleeping newborns and greater connectivity between the two regions, possibly indicating a potential for heightened fear conditioning and risk for future anxiety disorders (Lugo-Candelas et al. 2018).”

What the sources say

• Not checked yetcites Lugo-Candelas et al. 2018

In the paper

“improvement in mood during pregnancy is thought to diminish risks for postpartum depression and the associated effects on the child and to foster more positive representations of the child in utero that will carry over into the quality of the mother–child attachment system (Glover & Capron 2017).”

What the sources say

• Not checked yetcites Glover & Capron 2017

In the paper

“Pregestational diabetes and GDM have been associated with altered cognitive outcomes in the offspring (Adane et al. 2016) and with an increased risk for ASD (Sacks et al. 2016, Xiang et al. 2015).”

What the sources say

• Not checked yetcites Adane et al. 2016
• Not checked yetcites Sacks et al. 2016
• Not checked yetcites Xiang et al. 2015

In the paper

“This lack of diversity and representation in research samples is not only an ethical dilemma but also a scientific one, given that the effects of race and ethnicity on disease risk and treatment response are well documented.”

In the paper

“Psychological stress, anxiety, and depression are risk factors for infection (Cohen et al. 1991) as well as for diseases, such as diabetes (Hackett & Steptoe 2017), and hypertensive disorders, such as preeclampsia (Zhang et al. 2013),”

What the sources say

• Not checked yetcites Cohen et al. 1991
• Not checked yetcites Hackett & Steptoe 2017
• Not checked yetcites Zhang et al. 2013

In the paper

“Results indicated there was an independent effect of prenatal maternal distress on children’s risk for antisocial behavior and anxiety (i.e., the risk was present in both related and unrelated children) but not for ADHD (i.e., it was seen uniquely in children related to their mother) (Rice et al. 2010).”

What the sources say

• Not checked yetcites Rice et al. 2010

In the paper

“Further, it is important to acknowledge that exposures and mechanisms may exert an influence on each other, as we and others have observed to be the case for maternal nutrition and stress (Lindsay et al. 2019, Monk et al. 2013), and others have hypothesized for prenatal inflammation and the microbiome (Kim et al. 2017).”

What the sources say

• Not checked yetcites Lindsay et al. 2019
• Not checked yetcites Monk et al. 2013
• Not checked yetcites Kim et al. 2017

In the paper

“Hypertensive disorders during pregnancy are associated with higher risks of offspring developing behavioral problems, ADHD, affective disorder, and schizophrenia (reviewed in Dachew et al. 2018).”

What the sources say

• Not checked yetcites Dachew et al. 2018

In the paper

“With respect to feasibility and costs, it is terrifically challenging to assess, and thereby control for, the extent of postnatal influences on children’s development that might be foreshadowed by, and thus associated with, maternal prenatal distress.”

In the paper

“Experiencing multiple exposures may result in either additive or interactive effects that, if unaccounted for, may contribute to mixed findings in the literature.”

In the paper

“Because brain development begins before birth, parenting begins before birth (Glover & Capron 2017).”

What the sources say

• Not checked yetcites Glover & Capron 2017