Maternal Programming: Application of a Developmental Psychopathology Perspective

The fetal phase of life has long been recognized as a sensitive period of development. Here we posit that pregnancy represents a simultaneous sensitive period for the adult female with broad and persisting consequences for her health and development, including risk for psychopathology. In this review, we examine the transition to motherhood through the lens of developmental psychopathology. Specifically, we summarize the typical and atypical changes in brain and behavior that characterize the perinatal period. We highlight how the exceptional neuroplasticity exhibited by women during this life phase may account for increased vulnerability for psychopathology. Further, we discuss several modes of signaling that are available to the fetus to affect maternal phenotypes (hormones, motor activity, and gene transfer) and also illustrate how evolutionary perspectives can help explain how and why fetal functions may contribute to maternal psychopathology. The developmental psychopathology perspective has spurred advances in understanding risk and resilience for mental health in many domains. As such, it is surprising that this major epoch in the female life span has yet to benefit fully from similar applications

Women’s Pregnancy Life History and Alzheimer’s Risk: Can Immunoregulation Explain the Link?

Background: Pregnancy is associated with improvement in immunoregulation that persists into the geriatric phase. Impaired immunoregulation is implicated in Alzheimer’s disease (AD) pathogenesis. Hence, we investigate the relationship between pregnancy and AD. Methods: Cross-sectional cohort of British women (N = 95). Cox proportional hazards modeling assessed the putative effects of cumulative months pregnant on AD risk and the mutually adjusted effects of counts of first and third trimesters on AD risk. Results: Cumulative number of months pregnant, was associated with lower AD risk (β = −1.90, exp(β) = 0.15, P = .02). Cumulative number of first trimesters was associated with lower AD risk after adjusting for third trimesters (β = −3.83, exp(β) = 0.02, P \u3c .01), while the latter predictor had no significant effect after adjusting for the former. Conclusions: Our observation that first trimesters (but not third trimesters) conferred protection against AD is more consistent with immunologic effects, which are driven by early gestation, than estrogenic exposures, which are greatest in late gestation. Results may justify future studies with immune biomarkers

Intra-Individual Consistency in Endocrine Profiles Across Successive Pregnancies

Context: It is yet unknown how similar women’s hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women’s reproductive life-histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here we address this important lacuna in the literature. Objective: To investigate how consistent are women’s hormone profiles across two successive pregnancies. Design and Main Outcome Measures: This longitudinal, prospective study followed a cohort of 28 women across two pregnancies (PREG 1; PREG 2). Women’s circulating hormone levels were assessed from blood samples at 25, 31, and 37 weeks’ gestation for adrenocorticotropic hormone (ACTH), placental corticotropin-releasing hormone (pCRH), cortisol, estradiol, and progesterone. ACTH and cortisol levels were assessed 3-months postpartum. Research questions include: Are hormone levels in PREG 2 significantly different from levels in PREG 1?Whatproportion of variance in PREG 2 hormone levels is attributable to variance in PREG 1 levels? Are hormone levels more stable between PREG 1 and PREG 2 compared with postpartum phases following these pregnancies? Is pCRH, which is completely placentally derived, less similar than other hormones across successive pregnancies? Setting: Psychobiology laboratory. Participants: Pregnant women in California. Results and Conclusions: Comparisons of hormone concentrations across women’s successive pregnancies via paired t-test revealed substantial consistency from one pregnancy to another, with only significant differences between pregnancies for pCRH. Regressions revealed substantial predictability from one pregnancy to another, with between 17%–56% of PREG 2 variances accounted for by PREG 1 values. Women exhibited lower degrees of consistency and predictability in hormone levels across postpartum phases compared with gestational concentrations. This is the first study to describe maternal and placental hormone levels across successive pregnancies

A Longitudinal Study of Women’s Depression Symptom Profiles During and After the Postpartum Phase

Background An issue of critical importance for psychiatry and women\u27s health is whether postpartum depression (PPD) represents a unique condition. The Diagnostic and Statistical Manual of Mental Disorders asserts that major depressive disorder (MDD) may present with peripartum onset, without suggesting any other differences between MDD and PPD. The absence of any distinct features calls into question the nosologic validity of PPD as a diagnostic category. The present study investigates whether symptom profiles differ between PPD and depression occurring outside the postpartum phase. Methods In a prospective, longitudinal study of parturient women (N = 239), we examine the manifestation of depression symptoms. We assess factor structure of symptom profiles, and whether factors are differentially pronounced during and after the postpartum period. Results Factors were revealed representing: Worry, Emotional/Circadian/Energetic Dysregulation, Somatic/Cognitive, Appetite, Distress Display, and Anger symptoms. The factor structure was validated at postpartum and after‐postpartum timepoints. Interestingly, the Worry factor, comprising anxiety and guilt, was significantly more pronounced during the postpartum timepoint, and the Emotional/Circadian/Energetic Dysregulation factor, which contained sadness and anhedonia, was significantly less pronounced during the postpartum period. Conclusions These results suggest that PPD may be a unique syndrome, necessitating research, diagnosis, and treatment strategies distinct from those for MDD. Results indicate the possibility that Worry is an enhanced feature of PPD compared to depression outside the postpartum period, and the crucial role of sadness/anhedonia in MDD diagnosis may be less applicable to PPD diagnosis

Mothers’ Prenatal Distress Accelerates Adrenal Pubertal Development in Daughters

Human life history schedules vary, partly, because of adaptive, plastic responses to early-life conditions. Little is known about how prenatal conditions relate to puberty timing. We hypothesized that fetal exposure to adversity may induce an adaptive response in offspring maturational tempo. In a longitudinal study of 253 mother-child dyads followed for 15 years, we investigated if fetal exposure to maternal psychological distress related to children’s adrenarche and gonadarche schedules, assessed by maternal and child report and by dehydroepiandrosterone sulfate (DHEA-S), testosterone, and estradiol levels. We found fetal exposure to elevated maternal prenatal psychological distress predicted earlier adrenarche and higher DHEA-S levels in girls, especially first-born girls, and that associations remained after covarying indices of postnatal adversity. No associations were observed for boys or for gonadarche in girls. Adrenarche orchestrates the social-behavioral transition from juvenility to adulthood; therefore, significant findings for adrenarche, but not gonadarche, suggest that prenatal maternal distress instigates an adaptive strategy in which daughters have earlier social-behavioral maturation. The stronger effect in first-borns suggests that, in adverse conditions, it is in the mother’s adaptive interest for her daughter to hasten social maturation, but not necessarily sexual maturation, because it would prolong the duration of the daughter allomothering younger siblings. We postulate a novel evolutionary framework that human mothers may calibrate the timing of first-born daughters’ maturation in a way that optimizes their own reproductive success

Contact with Caregivers is Associated with Composition of the Infant Gastrointestinal Microbiome in the First 6 Months of Life

Objectives Little is known about how physical contact at birth and early caregiving environments influence the colonization of the infant gastrointestinal microbiome. We investigated how infant contact with caregivers at birth and within the first 2 weeks of life relates to the composition of the gastrointestinal microbiome in a sample of U.S. infants (n = 60). Methods Skin-to-skin and physical contact with caregivers at birth and early caregiving environments were surveyed at 2 weeks postpartum. Stool samples were collected from infants at 2 weeks, 2, 6, and 12 months of age and underwent 16S rRNA sequencing as a proxy for the gastrointestinal microbiome. Associations between early caregiving environments and alpha and beta diversity, and differential abundance of bacteria at the genus level were assessed using PERMANOVA, and negative binomial mixed models in DEseq2. Results Time in physical contact with caregivers explained 10% of variation in beta diversity at 2 weeks\u27 age. The number of caregivers in the first few weeks of life explained 9% of variation in beta diversity at 2 weeks and the number of individuals in physical contact at birth explained 11% of variation in beta diversity at 6 months. Skin-to-skin contact on the day of birth was positively associated with the abundance of eight genera. Infants held for by more individuals had greater abundance of eight genera. Discussion Results reveal a potential mechanism (skin-to-skin and physical contact) by which caregivers influence the infant gastrointestinal microbiome. Our findings contribute to work exploring the social transmission of microbes

Development of the Infant Gut Microbiome Predicts Temperament Across the First Year of Life

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment

The COS-Halos Survey: Physical Conditions and Baryonic Mass in the Low-Redshift Circumgalactic Medium

We analyze the physical conditions of the cool, photoionized (T $\sim 10^4$ K) circumgalactic medium (CGM) using the COS-Halos suite of gas column density measurements for 44 gaseous halos within 160 kpc of $L \sim L^*$ galaxies at $z \sim 0.2$. These data are well described by simple photoionization models, with the gas highly ionized (n$_{\rm HII}$/n$_{\rm H} \gtrsim 99\%$) by the extragalactic ultraviolet background (EUVB). Scaling by estimates for the virial radius, R$_{\rm vir}$, we show that the ionization state (tracked by the dimensionless ionization parameter, U) increases with distance from the host galaxy. The ionization parameters imply a decreasing volume density profile n$_{\rm H}$ = (10$^{-4.2 \pm 0.25}$)(R/R$_{\rm vir})^{-0.8\pm0.3}$. Our derived gas volume densities are several orders of magnitude lower than predictions from standard two-phase models with a cool medium in pressure equilibrium with a hot, coronal medium expected in virialized halos at this mass scale. Applying the ionization corrections to the HI column densities, we estimate a lower limit to the cool gas mass M$_{\rm CGM}^{\rm cool} > 6.5 \times 10^{10}$ M$_{\odot}$ for the volume within R $<$ R$_{\rm vir}$. Allowing for an additional warm-hot, OVI-traced phase, the CGM accounts for at least half of the baryons purported to be missing from dark matter halos at the 10$^{12}$ M$_{\odot}$ scale.Comment: 19 pages, 12 Figures, and a 37-page Appendix with 36 additional figures. Accepted to ApJ June 21 201