Cytokine concentrations throughout pregnancy and risk for psychosis in adult offspring: a longitudinal case-control study

Allswede, Dana; Yolken, Robert H.; Buka, Stephen L.; Cannon, Tyrone D.

doi:10.1016/s2215-0366(20)30006-7

Cited by 71 publications

(49 citation statements)

References 25 publications

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“…This study outcomes may have major implications on the clinical management of pregnant women in the state of Qatar. The main goal of this longitudinal cohort is to apply a multi-omics approach to understand the multifactorial causes of pregnancy complications and avoid the pitfalls generated by other studies that evaluated these factors separately [ 50 – 52 ]. The project will serve primarily to identify potential predictive diagnostic biomarkers for the early detection of pregnancy complications, as well as infant health and early-life causes of NCDs.…”

Section: Discussionmentioning

confidence: 99%

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar

Kumar

Saadaoui

Elhag

et al. 2021

BMC Pregnancy Childbirth

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Background Pregnancy is governed by multiple molecular and cellular processes, which might influence pregnancy health and outcomes. Failure to predict and understand the cause of pregnancy complications, adverse pregnancy outcomes, infant’s morbidity and mortality, have limited effective interventions. Integrative multi-omics technologies provide an unbiased platform to explore the complex molecular interactions with an unprecedented depth. The objective of the present protocol is to build a longitudinal mother-baby cohort and use multi-omics technologies to help identify predictive biomarkers of adverse pregnancy outcomes, early life determinants and their effect on child health. Methods/design : One thousand pregnant women with a viable pregnancy in the first trimester (6–14 weeks of gestation) will be recruited from Sidra Medicine hospital. All the study participants will be monitored every trimester, at delivery, and one-year post-partum. Serial high-frequency sampling, including blood, stool, urine, saliva, skin, and vaginal swabs (mother only) from the pregnant women and their babies, will be collected. Maternal and neonatal health, including mental health and perinatal growth, will be recorded using a combination of questionnaires, interviews, and medical records. Downstream sample processing including microbial profiling, vaginal immune response, blood transcriptomics, epigenomics, and metabolomics will be performed. Discussion It is expected that the present study will provide valuable insights into predicting pregnancy complications and neonatal health outcomes. Those include whether specific microbial and/or epigenomics signatures, immune profiles are associated with a healthy pregnancy and/or complicated pregnancy and poor neonatal health outcome. Moreover, this non-interventional cohort will also serve as a baseline dataset to understand how familial, socioeconomic, environmental and lifestyle factors interact with genetic determinants to influence health outcomes later in life. These findings will hold promise for the diagnosis and precision-medicine interventions.

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Section: Discussionmentioning

confidence: 99%

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar

Kumar

Saadaoui

Elhag

et al. 2021

BMC Pregnancy Childbirth

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“…Specifically, pregnant women are considered a risk group for developing severe symptoms upon SARS-CoV-2 infection ( Allotey et al, 2020 ). Activation of maternal immune response has, in turn, been repeatedly correlated with an increased risk for neurodevelopmental disorders in the offspring ( Meyer, 2019 ; Allswede et al, 2020 ).…”

Section: Viral Infections With Vertical Transmission From Mother To Fetusmentioning

confidence: 99%

The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids

Sarieva

Mayer

2021

Front. Mol. Biosci.

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Over the past decades, a growing body of evidence has demonstrated the impact of prenatal environmental adversity on the development of the human embryonic and fetal brain. Prenatal environmental adversity includes infectious agents, medication, and substances of use as well as inherently maternal factors, such as diabetes and stress. These adversities may cause long-lasting effects if occurring in sensitive time windows and, therefore, have high clinical relevance. However, our knowledge of their influence on specific cellular and molecular processes of in utero brain development remains scarce. This gap of knowledge can be partially explained by the restricted experimental access to the human embryonic and fetal brain and limited recapitulation of human-specific neurodevelopmental events in model organisms. In the past years, novel 3D human stem cell-based in vitro modeling systems, so-called brain organoids, have proven their applicability for modeling early events of human brain development in health and disease. Since their emergence, brain organoids have been successfully employed to study molecular mechanisms of Zika and Herpes simplex virus-associated microcephaly, as well as more subtle events happening upon maternal alcohol and nicotine consumption. These studies converge on pathological mechanisms targeting neural stem cells. In this review, we discuss how brain organoids have recently revealed commonalities and differences in the effects of environmental adversities on human neurogenesis. We highlight both the breakthroughs in understanding the molecular consequences of environmental exposures achieved using organoids as well as the on-going challenges in the field related to variability in protocols and a lack of benchmarking, which make cross-study comparisons difficult.

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“…The above findings suggest that an altered neuroimmune state could be a candidate endophenotype for BD and in particular it speaks about a neuro-immune-developmental pathogenesis of BD. In particular, an early proinflammatory state either during pregnancy (Allswede et al 2020 ) or adolescence (Mesman et al 2015 ; Snijders et al 2017 ) may perturb the fetal and young brain development shaping brain structures and in particular WM, followed by a virtually normalized immune state at adulthood with a background of continuously low-grade inflammation responsible of shortening telomere length and accelerated aging, leading to the characteristics symptoms of BD.…”

Section: Molecular Endophenotypesmentioning

confidence: 99%

Evaluating endophenotypes for bipolar disorder

Guglielmo

Hasler

2021

Int J Bipolar Disord

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Background Phenotypic heterogeneity is a major impediment to the elucidation of the neurobiology and genetics of bipolar disorder. Endophenotype could help in reducing heterogeneity by defining biological traits that are more direct expressions of gene effects. The aim of this review is to examine the recent literature on clinical, epidemiological, neurobiological, and genetic findings and to select and evaluate candidate endophenotypes for bipolar disorder. Evaluating putative endophenotype could be helpful in better understanding the neurobiology of bipolar disorder by improving the definition of bipolar-related phenotypes in genetic studies. In this manner, research on endophenotypes could be useful to improve psychopathological diagnostics in the long-run by dissecting psychiatric macro phenotypes into biologically valid components. Main body The associations among the psychopathological and biological endophenotypes are discussed with respect to specificity, temporal stability, heritability, familiarity, and clinical and biological plausibility. Numerous findings regarding brain function, brain structure, neuropsychology and altered neurochemical pathways in patients with bipolar disorder and their relatives deserve further investigation. Overall, major findings suggest a developmental origin of this disorder as all the candidate endophenotypes that we have been able to select are present both in the early stages of the disorder as well as in subjects at risk. Conclusions Among the stronger candidate endophenotypes, we suggest circadian rhythm instability, dysmodulation of emotion and reward, altered neuroimmune state, attention and executive dysfunctions, anterior cingulate cortex thickness and early white matter abnormalities. In particular, early white matter abnormalities could be the result of a vulnerable brain on which new stressors are added in young adulthood which favours the onset of the disorder. Possible pathways that lead to a vulnerable brain are discussed starting from the data about molecular and imaging endophenotypes of bipolar disorder.

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Cytokine concentrations throughout pregnancy and risk for psychosis in adult offspring: a longitudinal case-control study

Cited by 71 publications

References 25 publications

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar

The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids

Evaluating endophenotypes for bipolar disorder

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