Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence.

OBJECTIVE: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth. METHOD: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed. RESULTS: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy. CONCLUSION: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Association of prenatal modifiable risk factors with attention-deficit hyperactivity disorder outcomes at age 10 and 15 in an extremely low gestational age cohort.

Background: The increased risk of developing attention-deficit hyperactivity disorder (ADHD) in extremely preterm infants is well-documented. Better understanding of perinatal risk factors, particularly those that are modifiable, can inform prevention efforts. Methods: We examined data from the Extremely Low Gestational Age Newborns (ELGAN) Study. Participants were screened for ADHD at age 10 with the Child Symptom Inventory-4 (N = 734) and assessed at age 15 with a structured diagnostic interview (MINI-KID) to evaluate for the diagnosis of ADHD (N = 575). We studied associations of pre-pregnancy maternal body mass index (BMI), pregestational and/or gestational diabetes, maternal smoking during pregnancy (MSDP), and hypertensive disorders of pregnancy (HDP) with 10-year and 15-year ADHD outcomes. Relative risks were calculated using Poisson regression models with robust error variance, adjusted for maternal age, maternal educational status, use of food stamps, public insurance status, marital status at birth, and family history of ADHD. We defined ADHD as a positive screen on the CSI-4 at age 10 and/or meeting DSM-5 criteria at age 15 on the MINI-KID. We evaluated the robustness of the associations to broadening or restricting the definition of ADHD. We limited the analysis to individuals with IQ ≥ 70 to decrease confounding by cognitive functioning. We evaluated interactions between maternal BMI and diabetes status. We assessed for mediation of risk increase by alterations in inflammatory or neurotrophic protein levels in the first week of life. Results: Elevated maternal BMI and maternal diabetes were each associated with a 55-65% increase in risk of ADHD, with evidence of both additive and multiplicative interactions between the two exposures. MSDP and HDP were not associated with the risk of ADHD outcomes. There was some evidence for association of ADHD outcomes with high levels of inflammatory proteins or moderate levels of neurotrophic proteins, but there was no evidence that these mediated the risk associated with maternal BMI or diabetes. Conclusion: Contrary to previous population-based studies, MSDP and HDP did not predict ADHD outcomes in this extremely preterm cohort, but elevated maternal pre-pregnancy BMI, maternal diabetes, and perinatal inflammatory markers were associated with increased risk of ADHD at age 10 and/or 15, with positive interaction between pre-pregnancy BMI and maternal diabetes.

An exploration of posttraumatic growth, loneliness, depression, resilience, and social capital among survivors of Hurricane Katrina and the Deepwater Horizon Oil Spill.

The aim of this study was to examine the relationships among posttraumatic growth (PTG), loneliness, depression, psychological resilience, and social capital among survivors of Hurricane Katrina in 2005 and the Deepwater Horizon oil spill in 2010. The survey was administered to a spatially stratified, random sample of households in the three coastal counties of Mississippi. A total of 216 participants were included in this study who lived in close proximity to the Gulf of Mexico coastline during both disasters. Results from structural equation modeling analyses indicated that there was a significant and inverse relationship between PTG and loneliness. Conversely, a direct relationship was not found between PTG and depressive symptoms; instead, the results revealed an indirect relationship between PTG and depressive symptoms through loneliness. Social capital was related to loneliness only indirectly through PTG, while psychological resilience was related to loneliness both directly and indirectly through PTG. Understanding the relationships among these factors, particularly the importance of PTG, can provide insight into the long-term adaptation among those who have survived multiple disasters. Further, these findings may lead to nuanced methods for behavioral health practitioners in assessing and treating individuals with symptoms of depression in disaster-prone communities.

Community Resilience, Psychological Resilience, and Depressive Symptoms: An Examination of the Mississippi Gulf Coast 10 Years After Hurricane Katrina and 5 Years After the Deepwater Horizon Oil Spill.

OBJECTIVE: This study examined the role of community resilience and psychological resilience on depressive symptoms in areas on the Mississippi Gulf Coast that have experienced multiple disasters. METHODS: Survey administration took place in the spring of 2015 to a spatially stratified, random sample of households. This analysis included a total of 294 subjects who lived in 1 of the 3 counties of the Mississippi Gulf Coast at the time of both Hurricane Katrina in 2005 and the Deepwater Horizon oil spill in 2010. The survey included the Communities Advancing Resilience Toolkit (CART) scale, the Connor-Davidson Resilience Scale (CD-RISC 10), and the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: There was a significant inverse relationship between psychological resilience and depressive symptoms and a significant positive relationship between community resilience and psychological resilience. The results also revealed that community resilience was indirectly related to depressive symptoms through the mediating variable of psychological resilience. CONCLUSIONS: These findings highlight the importance of psychological resilience in long-term disaster recovery and imply that long-term recovery efforts should address factors associated with both psychological and community resilience to improve mental health outcomes. (Disaster Med Public Health Preparedness. 2018;12:241-248).

Adapting to Life after Hurricane Katrina and the Deepwater Horizon Oil Spill: An Examination of Psychological Resilience and Depression on the Mississippi Gulf Coast.

The purpose of this study was to examine relationships among depression, psychological resilience, and other sociodemographic factors of individuals who were highly exposed to Hurricane Katrina in 2005 and the Deepwater Horizon Oil Spill in 2010. A spatially stratified random sample of 294 Mississippi Gulf Coast residents living in close proximity to the Gulf of Mexico were surveyed. Findings indicated that low education attainment, financial hardship, and disaster-related damages increased the likelihood of depression, whereas psychological resilience and having health insurance reduced the odds of depression. Implications for enhancing psychological resilience and increasing access to health insurance are discussed.

Radiation dose to the lens during craniospinal irradiation-an improvement in proton radiotherapy technique.

PURPOSE: To evaluate the effect of angle modification of cranial field proton beam therapy on the radiation dose delivered to the lens during craniospinal irradiation (CSI). METHODS AND MATERIALS: Thirty-nine patients with central nervous system tumors who received CSI with a posterior fossa boost were analyzed for the radiation dose to the lens. Thirteen patients received cranial field treatment using standard opposed-lateral proton beams, and 26 patients received treatment with angled posterior-oblique proton beams. The lens dose in a test case also was evaluated by comparing conventional X-rays with the two proton beam planning methods by using a CMS/Xio three-dimensional planning system. RESULTS: Substantial lens dose sparing was realized with the angling of the cranial proton beams 15 degrees -20 degrees to the posterior. In the 39 treated patients who were analyzed (median age, 7 years), average dose delivered to the lens was decreased by approximately 50% by angling of the proton beams, with the average maximum dose decreasing from 74% to 40% of the prescribed dose (p < 0.0001). Significant lens sparing was seen in patients 10 years and younger (median age, 6 years; p < 0.0001), whereas an insignificant decrease was seen in older patients (median age, 16 years; p = 0.14). With the opposed-lateral technique (median age, 6 years), the lens dose increased significantly with decreasing age (p = 0.002), whereas there was no effect of age on lens dose in the angled beam-treated group (median age, 8.5 years; p = 0.73). CONCLUSION: The present study clearly shows an advantage in sparing of the lens dose by angling the beams used during proton beam CSI. This effect is most pronounced in patients 10 years and younger because of anatomic effects of sinus development.

Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models.

The role of placenta growth factor (PlGF) in pathologic angiogenesis is controversial. The effects of PlGF on growth, angiogenesis, and metastasis from orthotopic tumors are not known. To this end, we stably transfected three human cancer cell lines (A549 lung, HCT116 colon, and U87-MG glioblastoma) with human plgf-2 full-length cDNA. Overexpression of PlGF did not affect tumor cell proliferation or migration in vitro. The growth of PlGF-overexpressing tumors grown orthotopically or ectopically was impaired in all three tumor models. This decrease in tumor growth correlated with a decrease in tumor angiogenesis. The PlGF-overexpressing tumors had decreased vessel density and increased vessel diameter, but vessel permeability was not different from the parental tumors. Tumors overexpressing PlGF exhibited higher levels of PlGF homodimers and PlGF/vascular endothelial growth factor (VEGF) heterodimers but decreased levels of VEGF homodimers. Our study shows that PlGF overexpression decreases VEGF homodimer formation and inhibits tumor progression.

Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model.

Renal cell carcinoma is a highly malignant and often fatal disease of the kidney. It is difficult to treat, often because metastases are common at the time of presentation. Platelet-derived growth factor-D (PDGF-D) is a newly discovered member of the PDGF family; its function in tumor progression is largely unknown. Here, we examined the expression level of PDGF-D in human renal cell carcinoma by immunohistochemical staining using tissue arrays. We showed that human renal cell carcinoma expresses high levels of PDGF-D protein. The human renal cell carcinoma cell line SN12-C was stably transfected with pdgf-d cDNA. Overexpression of PDGF-D in SN12-C cells promoted tumor growth, angiogenesis, and metastasis of human renal cell carcinoma in an orthotopic severe combined immunodeficient (SCID) mouse model. PDGF-D overproduction in SN12-C cells increased the proliferation and migration of mural cells in vitro and improved perivascular cell coverage in vivo. Overexpression of PDGF-D led to increased expression of angiopoietin-1 and matrix metalloproteinase-9 in tumor tissues. ShRNAi and Gleevec were used to block PDGF-D expression and PDGF receptor beta (PDGFRbeta) signaling. Inhibition of PDGF-D expression by short hairpin RNA interference (shRNAi) and blockage of PDGFRbeta signaling by Gleevec inhibited the growth and lung metastasis of SN12-C cells grown orthotopically in SCID mice. Thus, PDGF-D is a potential candidate for controlling the progression of metastatic renal cell carcinoma. This opens up an avenue of investigation into novel therapeutic strategies for the treatment of renal cell carcinoma, including the use of recently developed tyrosine kinase inhibitors, such as Gleevec, which inhibit PDGF activity through inhibition of its receptor tyrosine kinase.