Fetal Origins of Mental Health: The Developmental Origins of Health and Disease Hypothesis.
01 Apr 2017-American Journal of Psychiatry (American Psychiatric AssociationArlington, VA)-Vol. 174, Iss: 4, pp 319-328
TL;DR: These findings parallel studies showing that antenatal maternal emotional well-being likewise predicts the risk for later psychopathology, and form the basis for integrative models of fetal neurodevelopment, which find little support for such integrated models.
Abstract: The quality of fetal growth and development predicts the risk for a range of noncommunicable, chronic illnesses. These observations form the basis of the "developmental origins of health and disease" hypothesis, which suggests that the intrauterine signals that compromise fetal growth also act to "program" tissue differentiation in a manner that predisposes to later illness. Fetal growth also predicts the risk for later psychopathology. These findings parallel studies showing that antenatal maternal emotional well-being likewise predicts the risk for later psychopathology. Taken together, these findings form the basis for integrative models of fetal neurodevelopment, which propose that antenatal maternal adversity operates through the biological pathways associated with fetal growth to program neurodevelopment. The authors review the literature and find little support for such integrated models. Maternal anxiety, depression, and stress all influence neurodevelopment but show modest, weak, or no associations with known stress mediators (e.g., glucocorticoids) or with fetal growth. Rather, compromised fetal development appears to establish a "meta-plastic" state that increases sensitivity to postnatal influences. There also remain serious concerns that observational studies associating either fetal growth or maternal mental health with neurodevelopmental outcomes fail to account for underlying genetic factors. Finally, while the observed relation between fetal growth and adult health has garnered considerable attention, the clinical relevance of these associations remains to be determined. There are both considerable promise and important challenges for future studies of the fetal origins of mental health.
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TL;DR: This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome.
653 citations
Cites background from "Fetal Origins of Mental Health: The..."
...Since it is important to give clear, unambiguous information about the type of stress measured in human prenatal stress studies (Graignic-Philippe et al., 2014; O’Donnell and Meaney, 2016), we include the name of the self-report or life event scales used and reported, or of the disaster exposed to, for studies reviewed in Tables 1-4 (cf....
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...Nevertheless, in DOHaD models that are based on preclinical research, maternal-fetal transfer of cortisol is thought to be the key pathway through which maternal stress is transferred to the fetus (O’Donnell and Meaney, 2016)....
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TL;DR: A multi‐scale framework for fundamental research on depression is proposed, aimed at identifying the brain circuits that are dysfunctional in several animal models of depression as well the changes in gene expression that are associated with these models.
286 citations
Cites background from "Fetal Origins of Mental Health: The..."
...genetic factors (Rasgon and McEwen, 2016) and stressful experiences before conception (Rodgers and Bale, 2015) and during gestation (Entringer et al., 2017; O’Donnell and Meaney, 2017) also have important influences....
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...Preconception epigenetic factors (Rasgon and McEwen, 2016) and stressful experiences before conception (Rodgers and Bale, 2015) and during gestation (Entringer et al., 2017; O’Donnell and Meaney, 2017) also have important influences....
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...Importantly, many of these reports reveal gender-dependent influences, with increased effects of childhood adversity on girls that are not unique to mental health outcomes (Buss et al., 2007; Buss et al., 2012; ODonnell and Meaney, 2017)....
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TL;DR: Elucidating the role of epigenetic mechanisms in intergenerational effects through prospective, multi‐generational studies may ultimately yield a cogent understanding of how individual, cultural and societal experiences permeate the authors' biology.
239 citations
TL;DR: FinnBrain syntymäkohorttitutkimus perustettiin tutkimaan erityisesti raskaudenaikaisten olosuhteiden and perimän yhteyksiä lapsen aivojen kehitykseen and terveyteen.
Abstract: Turun yliopiston FinnBrain syntymäkohorttitutkimus perustettiin tutkimaan erityisesti raskaudenaikaisten olosuhteiden ja perimän yhteyksiä lapsen aivojen kehitykseen ja terveyteen. Julkaistussa artikkelissa kuvataan tutkimuksen asetelma ja aineisto sekä keskeisimmät tutkimuskysymykset. Julkaisusarja on tarkoitettu erityisesti isojen kohorttitutkimusten kuvaamiseen. Artikkelissa kuvataan FinnBrain-aineisto: lasta odottavat äidit (n=3808), heidän puolisonsa (n=2623) ja tulevat lapsensa (n=3837;mukaan lukien 29 kaksosparia), jotka rekrytoitiin raskausviikolla 12 Lounais-Suomessa joulukuun 2011 ja huhtikuun 2015 välillä. Lisäksi kuvataan raskausajan arviointiin kuuluivat kyselylomakkeet (raskausviikot 14, 24, 24) sekä verinäytteet äidiltä ja isältä (raskausviikko 24) seerumin ja DNA:n analysoimiseksi. Lapsen syntymän jälkeen tutkittavia seurataan kyselylomakkeilla 3-36 kuukauden välein. Lisäksi nk. Fokuskohortissa verrataan raskaudenaikaista stressiä raportoineiden äitien lapsia ja heidän verrokkejaan käyttämällä esimerkiksi aivokuvantamista ja lapsen kehityksen neuropsykologisen toiminnan arviointia. Muissa alatutkimuksissa tutkitaan esimerkiksi hiuskortisolipitoisuuden merkitystä biomarkkerina, äidinmaidon ravintoaineja hormonipitoisuuksia sekä arvioidaan vanhempien neuropsykologisia toimintoja. Kaikkia osatutkimuksia ei ollut mahdollisuutta kuvata artikkelin puitteissa, vaan julkaisussa keskityttiin yleiskuvaan raskausaikana sekä ensimmäisen puolen vuoden aikana lapsen syntymän jälkeen.
155 citations
TL;DR: It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.
Abstract: There is clear evidence that the mother's stress, anxiety, or depression during pregnancy can alter the development of her fetus and her child, with an increased risk for later psychopathology. We are starting to understand some of the underlying mechanisms including the role of the placenta, gene-environment interactions, epigenetics, and specific systems including the hypothalamic-pituitary-adrenal axis and cytokines. In this review we also consider how these effects may be different, and potentially exacerbated, in different parts of the world. There can be many reasons for elevated prenatal stress, as in communities at war. There may be raised pregnancy-specific anxiety with high levels of maternal and infant death. There can be raised interpersonal violence (in Afghanistan 90.2% of women thought that "wife beating" was justified compared with 2.0% in Argentina). There may be interactions with nutritional deficiencies or with extremes of temperature. Prenatal stress alters the microbiome, and this can differ in different countries. Genetic differences in different ethnic groups may make some more vulnerable or more resilient to the effects of prenatal stress on child neurodevelopment. Most research on these questions has been in predominantly Caucasian samples from high-income countries. It is now time to understand more about prenatal stress and psychopathology, and the role of both social and biological differences, in the rest of the world.
143 citations
Cites background from "Fetal Origins of Mental Health: The..."
...Further, it does not seem that in general the effects on later psychopathology are mediated by effects of fetal growth (O’Donnell & Meaney, 2017)....
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References
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TL;DR: It is proposed that one of the major long-term consequences of inadequate early nutrition is impaired development of the endocrine pancreas and a greatly increased susceptibility to the development of Type 2 diabetes.
Abstract: In this contribution we put forward a novel hypothesis concerning the aetiology of Type 2 (non-insulin dependent) diabetes mellitus. The concept underlying our hypothesis is that poor foetal and early post-natal nutrition imposes mechanisms of nutritional thrift upon the growing individual. We propose that one of the major long-term consequences of inadequate early nutrition is impaired development of the endocrine pancreas and a greatly increased susceptibility to the development of Type 2 diabetes. In the first section we outline our research which has led to this hypothesis. We will then review the relevant literature. Finally we show that the hypothesis suggests a reinterpretation of some findings and an explanation of others which are at present not easy to understand.
3,107 citations
"Fetal Origins of Mental Health: The..." refers background in this paper
...These studies (1, 2) contributed to the emphasis on maternal health as a global priority for the World Health Organization (http://www....
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...The association between birth weight and cardiometabolic health catalyzed interest in the fetal origins of noncommunicable disease (1, 2)....
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TL;DR: A meta-analysis of 193 studies was conducted to examine the strength of the association between mothers’ depression and children’s behavioral problems or emotional functioning, with implications for theoretical models that move beyond main effects models in order to more accurately identify which children of depressed mothers are more or less at risk for specific outcomes.
Abstract: Although the association between maternal depression and adverse child outcomes is well established, the strength of the association, the breadth or specificity of the outcomes, and the role of moderators are not known This information is essential to inform not only models of risk but also the design of preventive interventions by helping to identify subgroups at greater risk than others and to elucidate potential mechanisms as targets of interventions A meta-analysis of 193 studies was conducted to examine the strength of the association between mothers’ depression and children’s behavioral problems or emotional functioning Maternal depression was significantly related to higher levels of internalizing, externalizing, and general psychopathology and negative affect/behavior and to lower levels of positive affect/behavior, with all associations small in magnitude These associations were significantly moderated by theoretically and methodologically relevant variables, with patterns of moderation found to vary somewhat with each child outcome Results are interpreted in terms of implications for theoretical models that move beyond main effects models in order to more accurately identify which children of depressed mothers are more or less at risk for specific outcomes
2,044 citations
TL;DR: Theoretical perspectives generate a novel hypothesis: that there is a curvilinear, U-shaped relation between early exposures to adversity and the development of stress-reactive profiles, with high reactivity phenotypes disproportionately emerging within both highly stressful and highly protected early social environments.
Abstract: Biological reactivity to psychological stressors comprises a complex, integrated, and highly conserved repertoire of central neural and peripheral neuroendocrine responses designed to prepare the organism for challenge or threat. Developmental experience plays a role, along with heritable, polygenic variation, in calibrating the response dynamics of these systems, with early adversity biasing their combined effects toward a profile of heightened or prolonged reactivity. Conventional views of such high reactivity suggest that it is an atavistic and pathogenic legacy of an evolutionary past in which threats to survival were more prevalent and severe. Recent evidence, however, indicates that (a) stress reactivity is not a unitary process, but rather incorporates counterregulatory circuits serving to modify or temper physiological arousal, and (b) the effects of high reactivity phenotypes on psychiatric and biomedical outcomes are bivalent, rather than univalent, in character, exerting both risk-augmenting and risk-protective effects in a context-dependent manner. These observations suggest that heightened stress reactivity may reflect, not simply exaggerated arousal under challenge, but rather an increased biological sensitivity to context, with potential for negative health effects under conditions of adversity and positive effects under conditions of support and protection. From an evolutionary perspective, the developmental plasticity of the stress response systems, along with their structured, context-dependent effects, suggests that these systems may constitute conditional adaptations: evolved psychobiological mechanisms that monitor specific features of childhood environments as a basis for calibrating the development of stress response systems to adaptively match those environments. Taken together, these theoretical perspectives generate a novel hypothesis: that there is a curvilinear, U-shaped relation between early exposures to adversity and the development of stress-reactive profiles, with high reactivity phenotypes disproportionately emerging within both highly stressful and highly protected early social environments.
1,725 citations
"Fetal Origins of Mental Health: The..." refers background in this paper
...The quality of intrauterine environment might explain, in part, the wide diversity among children in the degree to which developmental outcomes are influenced by prevailing context (84), a possibility that could inform and improve early interventions strategies....
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TL;DR: Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status.
Abstract: Context Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). Objective To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. Data Sources and Study Selection We searched for English-language and non–English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB ( Data Extraction Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. Data Synthesis Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. Conclusions Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.
1,552 citations
"Fetal Origins of Mental Health: The..." refers background in this paper
...birth outcome is strong in developing but not developed countries (53)....
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...Likewise, a meta-analysis examining maternal depression and birth weight (53) revealed a relation using categorical measures of depression, reflecting symptoms in the clinical range, but little or no association between birth weight and continuous measures of depressive symptoms, despite the fact that these same measures predict neurodevelopmental outcomes (see above)....
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TL;DR: A meta-analysis of observed differences in cognitive development between breast-fed and formula-fed children indicated that, after adjustment for appropriate key cofactors, breast-feeding was associated with significantly higher scores for cognitive development than was formula feeding.
1,231 citations
"Fetal Origins of Mental Health: The..." refers background in this paper
...The effect of breastfeeding on cognitive development is greater in low compared with normal birth weight children (85)....
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