Placental Gene Expression and Offspring Temperament Trajectories: Predicting Negative Affect in Early Childhood.

Exposure to prenatal stress increases offspring risk for long-term neurobehavioral impairments and psychopathology, such as Attention Deficit Hyperactivity Disorder (ADHD). Epigenetic regulation of glucocorticoid pathway genes may be a potential underlying mechanism by which maternal conditions 'program' the fetal brain for downstream vulnerabilities. The present study aims to investigate whether mRNA expression of glucocorticoid pathway genes in the placenta predict offspring negative affect during early childhood (between 6 and 24 months). Participants include 318 mother-child dyads participating in a longitudinal birth cohort study. Placental mRNA expression of glucocorticoid pathway genes (HSD11B1, HSD11B2, NR3C1, NCOR2) were profiled and negative affect traits of the offspring were measured at 6, 12, 18, and 24 months. HSD11B1 mRNA expression significantly predicted negative affect (ß = -.09, SE = .04; p = .036), and Distress to Limitations trajectories (ß = -.13, SE = .06; p = .016). NCOR2 mRNA expression significantly predicted Distress to Limitations (ß = .43, SE = .21; p = .047), and marginally predicted Sadness trajectories (ß = .39, SE = .21; p = .068). HSD11B2 and NR3C1 did not predict trajectories of Negative Affect or subscale scores. Infant negative affect traits were assessed via maternal self-report, and deviated from linearity across follow-up. mRNA expression of glucocorticoid pathway genes in the placenta may be a potentially novel tool for early identification of infants at greater risk for elevated negative affect. Further study is needed to validate the utility of mRNA expression of glucocorticoid pathway genes in the placenta.

Racial disparities in pre-operative pain, function and disease activity for patients with rheumatoid arthritis undergoing Total knee or Total hip Arthroplasty: a New York based study.

BACKGROUND: Black and Hispanic patients with osteoarthritis have more pain and worse function than Whites at the time of arthroplasty. Whether this is true for patients with rheumatoid arthritis (RA) is unknown. METHODS: This cross-sectional study used data on RA patients acquired between October 2013 and November 2018 prior to elective total knee (TKA) or hip arthroplasty (THA). Pain, function, and disease activity were assessed using the visual analogue scale (VAS), the Multidimensional Health Assessment Questionnaire (MDHAQ), and the Disease Activity Score (DAS28-ESR). We linked the cases to census tracts using geocoding to determine the community poverty level. Race, education, income, insurance and medications were collected via self-report. Using multivariable linear and logistic models we examined whether minority status predicted pain, function and RA disease activity at the time of arthroplasty. RESULTS: Thirty seven (23%) of the 164 patients were Black or Hispanic (minorities). The MDHAQ and DAS28-ESR were not significantly worse while VAS pain score was significantly worse in minority patients (p = 0.03). There was no significant difference in education between the groups. Insurance varied significantly; 29% of minority patients had Medicaid vs. 0% of Whites (p < 0.0001). In the multivariable analyses minority status was not significantly associated with DAS28-ESR [p = 0.66], MDHAQ [p = 0.26], or VAS pain [p = 0.18]. CONCLUSIONS: For Black and/or Hispanic patients with RA undergoing THA or TKA at a high-volume specialty hospital, unlike Black or Hispanic patients with osteoarthritis (OA), there was no association with worse pain, function, or RA disease activity at the time of elective arthroplasty.

The children of Superstorm Sandy: Maternal prenatal depression blunts offspring electrodermal activity.

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.

Prenatal Exposure to Famine and Risk for Development of Psychopathology in Adulthood: A Meta-Analysis.

Prenatal famine, resulting in intrauterine malnutrition, impacts offspring psychopathology later in adulthood. In addition, the specific impact of intrauterine malnutrition of different psychopathology differs by the timing of the exposure. Using a meta-analysis, the current study assessed the specific risk of developing affective, psychotic, and personality disorders. Studies were identified using PubMed and PsycINFO. Studies met the following criteria for inclusion in the analysis: availability in peer-reviewed English journals, use of human subjects, prenatal exposure to famine, and psychopathology in adulthood defined by diagnostic criteria as an outcome. Fixed effect relative risks (RRs) were calculated for affective, psychotic, and personality domains. Furthermore, timing of exposure was assessed as an effect modifier in our analysis, defined by the index trimester at the height of famine. Our meta-analysis found that adults exposed in utero during the 1st trimester were at a significant increased risk of psychotic disorders (RR=1.46, 95% CI=1.08, 1.97, p=0.014), and personality disorders (RR=2.31, 95% CI=1.36, 3.92, p=0.002). Those exposed during the 2nd trimester were at a significant increased risk of affective disorders (RR=1.45, 95% CI=1.22, 1.72, p<0.0001), and psychotic disorders (RR=1.46, 95% CI=1.13, 1.89, p=0.004). Similarly, those exposed in the 3rd trimester were at a significant increased risk of affective disorders (RR=1.33, 95% CI=1.13, 1.57, p=0.0001), and psychotic disorders RR=1.47, 95% CI=1.10, 1.97, p=0.010). Our findings suggest that there is differential risk across the different domains of psychopathology by trimester of exposures. This meta-analysis underscores the need for further investigation into the mechanisms underlying prenatal maternal nutrition and offspring psychopathology where magnitude of elevated risk differs by the exposure timing during pregnancy.

Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.