Prenatal Developmental Origins of Future Psychopathology: Mechanisms and Pathways

In the paper

“We have found higher levels of maternal distress related to greater fetal heart rate in response to stimuli, an early marker of heightened alertness (Posner et al. 2016).”

What the sources say

• Not checked yetcites Posner et al. 2016

In the paper

“Higher prenatal levels of maternal plasma corticotropin-releasing hormone are associated with greater cortical thinning and decrements in cognitive functioning in school-age children (Sandman et al. 2018).”

What the sources say

• Not checked yetcites Sandman et al. 2018

In the paper

“high maternal anxiety is associated with a twofold increase in the risk of probable mental disorder in children”

• Also stated in: § Maternal Prenatal Distress Is a Risk Factor for Future Psychopathology in Children · plain

  “High levels of maternal anxiety were associated with a twofold increased risk in probable mental disorder in male and female children at ages 4, 7, 9, 11.5, and 13 years.”

What the sources say

• Not checked yetcites O’Donnell et al. 2014

In the paper

“maternal distress across different gestational time points predicts behavioral problems in both males and females, such as externalizing or internalizing symptoms, anxiety, and depression, as well as conduct problems and overall psychiatric disturbances”

What the sources say

• Not checked yetcites van den Bergh et al. 2017

In the paper

“maternal distress is associated with children’s increased risk for psychopathology”

• Also stated in: § Maternal Prenatal Distress Is a Risk Factor for Future Psychopathology in Children · plain

  “elevated maternal distress during pregnancy increases the future child’s risk for mental health disorders, including anxiety, depression, ADHD, and schizophrenia”

What the sources say

• Not checked yetcites van den Bergh et al. 2017
• Not checked yetcites O’Donnell et al. 2014

In the paper

“Maternal infection also may be a risk factor for affective disorders in offspring (reviewed in Simanek & Meier 2015).”

What the sources say

• Not checked yetcites Simanek & Meier 2015

In the paper

“Several studies suggest that changes in placental DNA methylation at least partly mediate the effect of environmental factors on an offspring’s future risk for behavioral problems.”

In the paper

“studies find elevated serum levels of proinflammatory cytokines across trimesters in mothers with high psychological stress and low social support (Coussons-Read et al. 2007).”

What the sources say

• Not checked yetcites Coussons-Read et al. 2007

In the paper

“another found an association only between maternal distress and slightly lower awakening, and not diurnal, cortisol (N = 170 mothers) (van den Heuvel et al. 2018).”

What the sources say

• Not checked yetcites van den Heuvel et al. 2018

In the paper

“yet another found a positive association with overall cognition at 14 months (Spann et al. 2018).”

What the sources say

• Not checked yetcites Spann et al. 2018

In the paper

“results from one study indicated that maternal inflammation was related to decreased working memory at 24 months (Rudolph et al. 2018)”

What the sources say

• Not checked yetcites Rudolph et al. 2018

In the paper

“Juvenile and adult female offspring, however, had increased basal levels only in response to GD50 PS (Kapoor & Matthews 2008).”

What the sources say

• Not checked yetcites Kapoor & Matthews 2008

In the paper

“Maternal depression has been associated with greater placental DNA methylation of NR3C1, a gene encoding for a glucocorticoid receptor, and HSD11B2, a gene producing an enzyme that converts active cortisol into inactive cortisone.”

What the sources say

• Not checked yetcites Conradt et al. 2013

In the paper

“Studies on MIA in humans also document an increased risk for offspring psychopathology, notably ASD and schizophrenia.”

What the sources say

• Not checked yetcites Careaga et al. 2017

In the paper

“Another study showed an increased proportion of affective disorders occurring in children conceived during the influenza type A2/Singapore epidemic in Helsinki, Finland (Machon et al. 1997).”

What the sources say

• Not checked yetcites Machon et al. 1997

In the paper

“Birth cohorts and longitudinal studies have expanded our understanding of the fetal programing of the HPA axis, yet findings have been equivocal in associating maternal distress with HPA axis dysfunction and psychopathology.”

What the sources say

• Not checked yetcites Davis et al. 2011
• Not checked yetcites van den Heuvel et al. 2018

In the paper

“Together, these studies suggest that prenatal MIA exposure can impact the early development of the autonomic nervous system and brain networks involved in cognition, sensory processing, learning, and emotion.”

In the paper

“Abnormal functioning of the HPA axis is implicated in the pathophysiological mechanisms underlying a range of psychiatric illnesses (Buitelaar 2013).”

What the sources say

• Not checked yetcites Buitelaar 2013

In the paper

“Deregulation of this placental function has been shown to impact the offspring’s neurobehavioral development (Conradt et al. 2013, Monk et al. 2016, Paquette et al. 2014).”

What the sources say

• Not checked yetcites Conradt et al. 2013
• Not checked yetcites Monk et al. 2016
• Not checked yetcites Paquette et al. 2014

In the paper

“The relation between MIA and compromised neurodevelopmental and psychiatric functioning has been widely investigated in recent years, with both animal models and studies in humans predominantly supporting such an association.”

In the paper

“juvenile and adult male guinea pigs exposed to late-gestation PS [gestational day (GD) 50 or 60; gestation length approximately 65–70 days] had increased basal and adrenocorticotropic hormone–stimulated cortisol levels (Kapoor & Matthews 2005).”

What the sources say

• Not checked yetcites Kapoor & Matthews 2005

In the paper

“Animal models support MIA leading to increased risk for psychopathology in offspring. Findings include symptoms and behaviors representative of autism (Kang et al. 2014), schizophrenia (Li et al. 2009), and anxiety and depression (Depino 2018).”

What the sources say

• Not checked yetcites Kang et al. 2014
• Not checked yetcites Li et al. 2009
• Not checked yetcites Depino 2018

In the paper

“The placenta regulates fetal cortisol exposure, in part via placental DNA methylation of glucocorticoid-related genes such as FKBP5, HSD11B2, and NR3C1.”

What the sources say

• Not checked yetcites Conradt et al. 2013
• Not checked yetcites Monk et al. 2016
• Not checked yetcites Paquette et al. 2014

In the paper

“In humans, placental DNA methylation of FKBP5 (FK506 binding protein, a molecular chaperone of glucocorticoid receptor regulation) has been associated with reduced placental FKBP5 gene expression and increased risk of high arousal in newborns (N = 61, 49% female) (Paquette et al. 2014).”

What the sources say

• Not checked yetcites Paquette et al. 2014

In the paper

“A recent meta-analysis supports small-to-moderate effects of maternal distress on an offspring’s glucocorticoid levels across preclinical and human studies (Thayer et al. 2018).”

What the sources say

• Not checked yetcites Thayer et al. 2018

In the paper

“A recent review (Depino 2018) underscores these issues by documenting that in animal models the specific methodology used to elicit maternal perinatal inflammation often results in different symptomatology.”

What the sources say

• Not checked yetcites Depino 2018

In the paper

“In human pregnancies, one study found a decrease in placental mitochondrial copy number with exposure to prenatal stress (Brunst et al. 2017).”

What the sources say

• Not checked yetcites Brunst et al. 2017

In the paper

“one study found initial increases in early offspring cortisol reactivity (at 5 weeks), but decreases in later reactivity (at 8 weeks and 12 months); stressors have varied across offspring assessments, possibly contributing to the variability (Tollenaar et al. 2011).”

What the sources say

• Not checked yetcites Tollenaar et al. 2011

In the paper

“In one elegant model in mice based on the X-linked gene OGT (O-linked N-acetylglucosamine transferase), male placentas with typically lower levels of OGT are poised for epigenetic alterations that appear to produce robust transcriptional responses to maternal prenatal stress that result in increased stress sensitivity as adults (Bale 2016).”

What the sources say

• Not checked yetcites Bale 2016 source

In the paper

“Because the foundations of the central nervous system develop prenatally, variations originating from this critical period will impact subsequent neural network patterns and have significant relevance for neurobehavioral development (Anderson & Thomason 2013).”

What the sources say

• Not checked yetcites Anderson & Thomason 2013

In the paper

“as Glover (2011) summarizes, children’s outcomes related to prenatal exposure to maternal distress—anxiety, ADHD, impulsivity, aggression—may have been adaptive in life-threatening environments by increasing vigilance and prioritizing attunement to danger cues, more exploration, and a willingness to fight predators.”

What the sources say

• Not checked yetcites Glover 2011

In the paper

“Mitochondria are involved in the one-carbon metabolism pathway that uses nutrients from the diet to provide methyl (CH3) groups for the methylation of DNA (Bao et al. 2016).”

What the sources say

• Not checked yetcites Bao et al. 2016

In the paper

“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.”

In the paper

“It is important to consider that maternal stress—versus a subclinical or clinical infection—may have a more pervasive inflammatory profile, as studies find elevated serum levels of proinflammatory cytokines across trimesters in mothers with high psychological stress and low social support (Coussons-Read et al. 2007).”

What the sources say

• Not checked yetcites Coussons-Read et al. 2007

In the paper

“In one study, prairie voles exposed to prenatal maternal stress showed varying levels of behavioral and physiological stress reactivity as adults, depending on the quality of their rearing environments, while controls showed no effect of rearing condition (Hartman et al. 2018).”

What the sources say

• Not checked yetcites Hartman et al. 2018

In the paper

“This assertion of the fetal origins of future development as relevant to mental health commenced, in part, with the Fels Longitudinal Study in the 1930s”

What the sources say

• Not checked yetcites DiPietro et al. 2015 source

In the paper

“sex as it moderates fetal brain development and placental functioning [and possibly maternal stress biology (DiPietro et al. 2011)] is central to characterizing prenatal programming processes and neurobehavioral trajectories”

What the sources say

• Not checked yetcites DiPietro et al. 2011

In the paper

“the Iowa Flood Study of pregnant women found increased cortisol in response to stress in female toddlers, but not in male toddlers (aged 2.5 years) (Yong Ping et al. 2015).”

What the sources say

• Not checked yetcites Yong Ping et al. 2015

In the paper

“there is significant variation in outcomes depending on the timing of inflammation, even when the methods utilized to elicit it are kept constant (Li et al. 2009).”

What the sources say

• Not checked yetcites Li et al. 2009

In the paper

“there is a lack of specificity with respect to the gestational timing of prenatal maternal distress and differentiated child outcomes (van den Bergh et al. 2017).”

What the sources say

• Not checked yetcites van den Bergh et al. 2017

In the paper

“and increased expression was negatively correlated with infant temperament indices of activity, smile, and laughter at 6 months of age (Lambertini et al. 2015).”

What the sources say

• Not checked yetcites Lambertini et al. 2015

In the paper

“In addition, mitochondrial signaling regulates gene expression in the cell nucleus and the DNA methylation machinery, DNA methyltransferases, which contribute to DNA methylation and transcriptional reprogramming in the placenta (Picard et al. 2014).”

What the sources say

• Not checked yetcites Picard et al. 2014

In the paper

“Sex differences identifying greater male vulnerability point to the slower development of the male brain—such that there is an extended critical period of prenatal vulnerability—as an explanatory model”

In the paper

“higher self-reported trait anxiety, state anxiety, and perceived stress were associated with increased MT-ND2 gene expression,”

What the sources say

• Not checked yetcites Lambertini et al. 2015

In the paper

“It has become increasingly evident that the gut microbiome has a significant role in health and disease, including in neurodevelopment and psychiatric functioning (Lima-Ojeda et al. 2017).”

What the sources say

• Not checked yetcites Lima-Ojeda et al. 2017

In the paper

“Studies of prenatal maternal sleep deprivation (MSD) have consistently documented compromised development and functioning in offspring of dams with MSD.”

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

“A study from our group showed that in a sample of 292 teenage mothers (ages 14–19 years), emotional abuse during childhood was indirectly associated with lower third-trimester fetal heart rate variability via abuse-related maternal sleep disturbances throughout pregnancy (Gustafsson et al. 2017).”

What the sources say

• Not checked yetcites Gustafsson et al. 2017

In the paper

“For example, one study of 74 mothers found evidence for delays in social development in 1-year-olds born to mothers who experienced sleep-disordered breathing during pregnancy (Tauman et al. 2015).”

What the sources say

• Not checked yetcites Tauman et al. 2015

In the paper

“In animals, maternal consumption of a high-fat diet during gestation has been associated with hyperactivity, anxiety-like behavior, depressive behavior, and cognitive delays in the offspring (Sullivan et al. 2015).”

What the sources say

• Not checked yetcites Sullivan et al. 2015

In the paper

“Decades of innovative work have demonstrated late-term fetal discrimination of various sound categories, including musical tones and short melodies (Busnel et al. 2017),”

What the sources say

• Not checked yetcites Busnel et al. 2017

In the paper

“Rodent models show early and late gestational stress resulting in Lactobacillus depletion in both the maternal vaginal microbiome and the offspring’s gut microbiome (Gur et al. 2017),”

What the sources say

• Not checked yetcites Gur et al. 2017

In the paper

“A study in nonhuman primates demonstrated that the offspring of prenatally stressed mothers showed altered gut microbiomes (Bailey et al. 2004).”

What the sources say

• Not checked yetcites Bailey et al. 2004

In the paper

“The availability of methyl donors, such as folate and choline, as well as cofactors, including zinc and vitamins B2, B6, and B12, is essential for typical DNA methylation and placental function (Niculescu & Zeisel 2002).”

What the sources say

• Not checked yetcites Niculescu & Zeisel 2002

In the paper

“Preclinical studies provide some evidence of probiotic administration influencing concentrations of inflammatory cytokines, gamma-aminobutyric acid, glutamate, and brain-derived neurotrophic factor, all of which play important parts in cognitive functioning and are implicated across psychiatric diseases (Cerdó et al. 2017).”

What the sources say

• Not checked yetcites Cerdó et al. 2017

In the paper

“the maternal microbiome may be another plausible pathway for prenatal maternal stress to exert an influence on an offspring’s neurodevelopment (Culhane et al. 2001).”

What the sources say

• Not checked yetcites Culhane et al. 2001

In the paper

“Importantly, no direct human evidence of in utero infant gut colonization exists (although see Oki et al. 2018 for emerging work in this area).”

What the sources say

• Not checked yetcites Oki et al. 2018

In the paper

“Deficiencies in folate, vitamin B12, calcium, iron, selenium, zinc, and magnesium have been associated with symptoms of depression in pregnant women (Leung & Kaplan 2009, Singh et al. 2017).”

What the sources say

• Not checked yetcites Leung & Kaplan 2009
• Not checked yetcites Singh et al. 2017

In the paper

“Microbiota colonize the infant gut and guide critical processes, such as metabolism and nutrient extraction (Cilieborg et al. 2012).”

What the sources say

• Not checked yetcites Cilieborg et al. 2012

In the paper

“Stress and depressive symptoms have been shown to alter eating patterns, resulting in increased selection of less-nutritious food, particularly food high in fat and sugar, and processed foods, and decreased selection of fruits and vegetables (reviewed in Baskin et al. 2015).”

What the sources say

• Not checked yetcites Baskin et al. 2015

In the paper

“As prenatal stress is known to alter the composition of the maternal microbiota, the maternal microbiome may be another”

What the sources say

• Not checked yetcites Culhane et al. 2001

In the paper

“That is, maternal distress may be a marker variable for unexamined subclinical health and lifestyle factors that also affect fetal and child development.”

In the paper

“Alterations in the composition of the gut microbiota have been found in clinical populations, including populations with depression, stress, anxiety, and autism (Cenit et al. 2017).”

What the sources say

• Not checked yetcites Cenit et al. 2017

In the paper

“Concerns about the long-term effects of maternal prenatal malnutrition initially arose from epidemiological studies of the Dutch famine (1944–1945) showing that children conceived during a period of starvation had a higher risk of disease later in life, including neurodevelopmental disorders such as schizophrenia (Hoek et al. 1998).”

What the sources say

• Not checked yetcites Hoek et al. 1998

In the paper

“compared with control piglets whose mothers did not undergo manipulation and with those exposed to the voice paired with positive brushing, those exposed to the voice paired with maternal aversive prenatal treatment emitted more distress calls.”

What the sources say

• Not checked yetcites Tallet et al. 2016

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

“The majority of studies of prenatal distress control for potential confounds such as postpartum maternal depression and the quality of parenting (van den Bergh et al. 2017).”

What the sources say

• Not checked yetcites van den Bergh et al. 2017

In the paper

“Until the field moves toward including assessments of multiple, simultaneous exposures, particularly for exposures that tend to co-occur frequently, DOHaD studies of the effects of maternal distress will lack ecological validity and rigor.”

In the paper

“The quality of the father’s sperm also influences development (Dias & Ressler 2014),”

What the sources say

• Not checked yetcites Dias & Ressler 2014

In the paper

“Decades of epidemiological, clinical translational, and preclinical animal research have converged, demonstrating that maternal prenatal distress affects fetal brain–behavior development and influences children’s neurobehavioral trajectory, often increasing their risk for psychopathology.”

In the paper

“Oberlander et al. (2010) have found that prenatal maternal distress interacts with a child’s 5-HTTLPR genotype—which codes for the serotonin transporter gene—in predicting offspring’s behavioral dysregulation.”

What the sources say

• Not checked yetcites Oberlander et al. 2010

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

“Some studies have investigated the effect of maternal prenatal distress while controlling for parental history of psychiatric symptoms as a proxy for genetic vulnerability and showed an independent effect of prenatal maternal distress on children’s risk for psychopathology (e.g., MacKinnon et al. 2018).”

What the sources say

• Not checked yetcites MacKinnon et al. 2018

In the paper

“Decades of epidemiological, clinical translational, and preclinical animal research have converged, demonstrating that maternal prenatal distress affects fetal brain–behavior development and influences children’s neurobehavioral trajectory, often increasing their risk for psychopathology.”

In the paper

“However, it is important to note that rodent models of PS, which aim to control for genetic strain, consistently show independent effects of PS exposure in offspring on brain–behavior outcomes (van den Bergh et al. 2017).”

What the sources say

• Not checked yetcites van den Bergh et al. 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

“Prior to this policy directive, prescriptions of selective serotonin reuptake inhibitors (SSRIs) to pregnant women already had increased four- to eightfold during the past 30 years (Lugo-Candelas et al. 2018).”

What the sources say

• Not checked yetcites Lugo-Candelas et al. 2018

In the paper

“For example, we found that maternal untreated depression was associated with increased inverse functional connectivity between the amygdala and dorsal prefrontal cortex in sleeping, nonsedated young infants (Posner et al. 2016).”

What the sources say

• Not checked yetcites Posner et al. 2016

In the paper

“Decades of epidemiological, clinical translational, and preclinical animal research have converged, demonstrating that maternal prenatal distress affects fetal brain–behavior development and influences children’s neurobehavioral trajectory, often increasing their risk for psychopathology.”

In the paper

“However, many human studies have been criticized for confounding by indication—that is, the difficulty of specifying children’s altered brain–behavior development as the result of SSRI exposure via changes in 5-HT signaling or the indication (e.g., maternal depression) that precipitated the SSRI use and its associated factors, or some of both (Oberlander & Vigod 2016).”

What the sources say

• Not checked yetcites Oberlander & Vigod 2016

In the paper

“Children’s behavioral outcomes may be more or less impacted by prenatal maternal distress based on interindividual maternal genetic variability, leading to either increased susceptibility or protective influences.”

In the paper

“It is unfortunate that even after passing S.1, the National Institutes of Health Revitalization Act of 1993, the past two decades have not seen increases in minority participation that parallel their distributions in the US population (Burchard et al. 2015, Oh et al. 2015).”

What the sources say

• Not checked yetcites Burchard et al. 2015
• Not checked yetcites Oh et al. 2015