Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes
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PROVIDER: PRJNA472864 | ENA |
REPOSITORIES: ENA
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Project description:Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We analyzed transcriptome-wide gene expression profiles of 149 UCB samples from neonates born to mothers with prenatal PTSD (n=20), depression (n=31) and PTSD with comorbid depression (PTSD/Dep; n=13), compared to neonates born to carefully matched trauma exposed controls without meeting PTSD criteria (TE; n=23) and healthy mothers (n=62). We also evaluated physiological and developmental measures in these infants at birth, six months and twenty-four months. A multistep analytic approach was used that specifically sought to: 1) identify dysregulated genes, molecular pathways and discrete groups of co-regulated gene modules in UCB associated with prenatal maternal psychopathologies; and 2) to determine the impact of perinatal PTSD and depression on early childhood development outcomes.
2018-05-25 | GSE114852 | GEO
Project description:The purpose of this study is to describe type and extent of psychological distress (adverse effects) in patients undergoing surgery for colorectal cancer with peritoneal metastases and after surgery for colorectal cancer with involvement of the urinary bladder.
| 2382857 | ecrin-mdr-crc
Project description:Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n?=?20), depression (n?=?31) and PTSD with comorbid depression (n?=?13), compared to carefully matched trauma exposed controls (n?=?23) and healthy mothers (n?=?62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.
| S-EPMC6191930 | biostudies-literature
Project description:Interventions: Targeted selection of patients with psychological distress. Enhanced care
by the clinical nurse specialist. Stepped care: The steps include: (i) Watchful waiting. (ii) If psychological distress persists, the guided self-help program. (iii) If psychological distress persists, a problem analysis is performed and an agreement is made with the patient on the next step; treatment consists of problem solving therapy (face-to-face). (iv) If psychological distress persists, psychotherapy, medication or a referral for other services (e.g. social work) is offered.
The TES intervention is compared to usual care.
Primary outcome(s): Psychological distress:
- Hospital Anxiety and Depression Scale (HADS)
Study Design: Randomized controlled trial, Single blinded (masking used), Active, Parallel
| 18256 | ecrin-mdr-crc
Project description:Micronutrient deficiencies and environmental exposures have been to known to adversely impact brain and nervous system functions in adults and children worldwide. However, few studies have examined the short and long-term impact of these risk factors on neurodevelopmental outcomes in children in low-income countries, where the effects are likely to be more pronounced due to limited resources for monitoring and insufficient regulations. Biological risk factors of relevance include micronutrient deficiencies such as zinc and exposure to heavy metals such as lead and mercury. Studies have suggested an association between neurodevelopmental impairment and micronutrient deficiency as well as exposure to a number of heavy metals and environmental toxins. Moreover, findings also suggest that risk factors for adverse developmental outcomes that are independently significant may have the potential for causing cumulative increases in adverse effects. In Sub-Saharan Africa, severe malaria is a leading risk factor for long-term neurocognitive impairment in children. Zinc deficiency or exposure to heavy metals could influence risk of severe malaria, modify the risk of neurocognitive impairment in children with severe malaria, or independently affect risk of neurocognitive impairment. Untargeted analyses for potential environmental exposures or metabolomic changes in children with cerebral malaria vs. without cognitive impairment or in children with higher vs. lower cognitive scores, could also identify new risk factors for neurodevelopmental impairment in Ugandan children with cerebral malaria.In our completed study in Kampala, we assessed neurologic and developmental impairment in children with cerebral malaria [CM] or severe malarial anemia [SMA], as compared to health community children from the same extended household as the children with CM or SMA. As an extension of this study, we are interested in determining levels of micronutrients such as zinc in the population, and in addition, determining exposure levels of heavy metals (lead, mercury, copper, manganese etc.) in samples collected from children with severe malaria and community controls. The primary hypotheses of this study is that nutrient deficiencies or exposure to heavy metals influence short and long term neurocognitive outcomes in healthy community children and in children with severe malaria, and that children with cerebral malaria have specific metabolomic changes that relate to long-term neurocognitive impairment. The specific aims of our study are:Aim 1: To determine levels of zinc, heavy metals, and biomarkers associated with inflammation in children presenting with different forms of severe malaria (SM) and in healthy community children (CC). The working hypothesis of this aim is that 1) children with SM will have lower zinc levels compared to CC; 2) children with SM will present with higher toxic metal exposure and higher levels of biomarkers associated with inflammation than CC.Aim 2: To investigate how micronutrient deficiency, toxic metal exposure and inflammatory biomarkers affect short and long term neurodevelopmental outcomes and growth in children with severe malaria and community children (CC).The working hypothesis of this aim is that the lower levels of zinc, and presence of toxic metals in high concentrations will independently contribute to worsening neurodevelopmental outcomes and worsening growth over time in children with severe malaria and in community children. An alternate hypothesis is that micronutrient deficiency, toxic metal exposure and inflammatory states may interact with each other and with severe malaria to produce greater neurodevelopmental impairment, i.e., that the contribution is not independent but interactive.Aim 3: To determine whether the CSF metabolome differs according to level of neurodevelopmental impairment in children with cerebral malaria. The working hypothesis of this aim is that neurodevelopmental impairment in children with cerebral malaria is associated with changes in the CSF metabolome.
2017-09-27 | ST000877 | MetabolomicsWorkbench
Project description:Prenatal exposure to the anti-seizure drug sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. First, we assessed the effect of gestational VPA on fetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses which are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied - inbred Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic generalized epilepsy, and inbred Non-Epileptic Control (NEC) rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Fetuses were extracted via C-section on gestational day 21 (one day prior to birth) and fetal brains were snap frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The set of genes down-regulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function, and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic fetal VPA exposure and adverse neurodevelopmental outcomes mediated by VPA-induced transcriptional dysregulation.
2022-05-08 | GSE198756 | GEO
Project description:Blood plasma was collected from 9 naval aviation students 24 hours prior to and no more than 20 minutes after Modular Egress Training (psychological stressor).
2009-12-01 | PRD000158 | Pride
Project description:Individual differences in basal leukocyte gene expression profiles as a function of hedonic and eudaimonic well-being, and psychological and social sub-dimensions of eudaimonic well-being. Gene expression profiling was carried out on peripheral blood mononuclear cell RNA samples collected from 122 healthy adults measured for hedonic and eudaimonic dimensions of well-being using the Short Flourishing Scale (Keyes, C (2014). The Mental Health Continuum-Short Form (MHC-SF) for adults). Higher values of the hedonic well-being scale indicate greater levels of positive affect, higher values of eudaimonic well-being scale indicate greater experience of purpose and meaning in life, higher values of social well-being scale indicate greater experience of social well-being in life, higher values of psychological well-being scale indicate greater experience of psychological well-being in life, greater TotalMHCSF scores indicate greater experience of all forms of well-being measured by the MHC-SF, the FlourishGroup indicates idividuals showing flourishing mental health as defined by the MHC-SF scoring instructions referenced above, greater BrownPsychological scores indicate greater experience of psychological well-being as measured by the MHC-SF with an alternative scoring, and greater BrownSocial scores indicate greater experience of social well-being as measured by the MHC-SF with an alternative scoring.
2015-03-28 | E-GEOD-55762 | biostudies-arrayexpress
Project description:BackgroundExposure to adverse childhood experiences (ACEs) constitutes public health problems linked to adverse mental outcomes such as psychological distress during adulthood. This study examines the prevalence of ACEs and psychological distress and explores the association between ACEs and psychological distress and demographic factors among young adults.MethodsWe conducted a cross-sectional study of 330 students from May 2018 to July 2018. The participants completed the Adverse Childhood Experiences International Questionnaire (ACE-IQ), Kessler Psychological Distress Scale (K10), and the sociodemographic profile scale. We used descriptive statistics to describe the prevalence of ACEs and psychological distress in our sample. After adjusting for the demographic covariates, ACEs' association with psychological distress was determined using binary and multivariate logistic regressions.ResultsA total of 203 students with a mean age of 20.76 ± 2.73 years completed the study. The total mean ACE score was 4.58 ± 1.59, and the total mean psychological distress score was 20.76 ± 6.31. Most of the participants (86.7%) experienced ACEs, 14.8% reported experiencing one ACE, 30.5% reported experiencing 2-3 ACEs, and 41.3% reported experiencing 4+ ACEs. Further, about 85% of the youth have experienced at least one form of sexual abuse during childhood, and females reported a higher number of ACEs than males. Sexual abuse (OR = 2.36; 95% CI: 2.36, 7.65), physical neglect (OR = 2.87; 95% CI: 1.57, 5.31), overall ACE exposure (OR = 6.66; 95% CI: 2.41, 18.42), having 1 ACE (OR = 4.40; 95% CI: 1.32, 14.70), having 2-3 ACEs (OR = 4.13; 95% CI: 1.39, 12.29), and having 4+ (OR = 11.67; 95% CI: 3.95, 34.45) were significantly associated with psychological distress.ConclusionsACEs are prevalent among young adults and are associated with psychological distress in adulthood. Furthermore, parental factors are associated with ACEs and psychological distress. Thus, implementation of school, community-and facility-based routine mental health screening programs is essential for prompt identification, prevention, and treatment of youth with childhood adversities and poor mental health outcomes.
| S-EPMC8086118 | biostudies-literature
Project description:BackgroundAdverse childhood experiences (ACES) have been linked to poor health and well-being outcomes, including poor mental health such as psychological distress. Both ACEs and psychological distress pose a significant public health burden, particularly in low to middle income countries. Contemporaneous stress events in adulthood may also impact psychological distress. The aims of this study were to describe the prevalence of ACEs and psychological distress and to assess the separate and cumulative effect of ACEs on psychological distress, while accounting for the effect of adult stress.MethodsIn this cross-sectional study, we used retrospectively measured ACEs from a sample of 1223 young adults aged between 22 and 23 years (52% female) from the Birth to Twenty Plus Study. Psychological distress and adult life stress were measured with a six-month recall period. Hierarchical logistic regression was employed to assess the associations between the exposures and outcome.ResultsNearly 90% of the sample reported at least one ACE and 28% reported psychological distress. The median number of ACEs reported was three (range 0-11). After accounting for demographic and socio-economic factors, all ACEs were individually associated with psychological distress except for parental divorce and unemployment. The individual ACEs increased the odds of PD by between 1.42 and 2.79 times. Compared to participants experiencing no ACEs, those experiencing one to five ACEs were three times more likely to report psychological distress (AOR 3.2 95% CI: 1.83-5.63), while participants who experienced six or more ACEs had nearly eight times greater odds of reporting psychological distress (AOR 7.98 95% CI: 4.28-14.91). Interaction analysis showed that in the absence of adult life stress, the effect of low ACEs compared to high ACEs on PD was not significantly different.Discussion and conclusionThe prevalence of ACEs in this young adult population is high, similar to other studies in young adult populations. A significant direct association exists between ACEs and psychological distress. Adult life stress seems to be a mediator of this relationship. Interventions targeted at psychological distress should address both early life adversity and contemporary stress.
| S-EPMC6034311 | biostudies-literature