Dataset Information

Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

ABSTRACT: Importance:The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero. Objective:To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy. Design, Setting, and Participants:A total of 1?791?520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018. Exposures:Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection. Main Outcomes and Measures:Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring. Results:A total of 1?791?520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32?125?813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero. Conclusions and Relevance:These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.

SUBMITTER: Al-Haddad BJS

PROVIDER: S-EPMC6551852 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

Al-Haddad Benjamin J S BJS Jacobsson Bo B Chabra Shilpi S Modzelewska Dominika D Olson Erin M EM Bernier Raphael R Enquobahrie Daniel A DA Hagberg Henrik H Östling Svante S Rajagopal Lakshmi L Adams Waldorf Kristina M KM Sengpiel Verena V

JAMA psychiatry 20190601 6

<h4>Importance</h4>The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero.<h4>Objective</h4>To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy.<h4>Design, setting, and participants</h4>A total of ...[more]

PMID: 30840048

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Project description:Importance:Emerging yet contrasting evidence associates air pollution with incident dementia, and the potential role of cardiovascular disease (CVD) in this association is unclear. Objective:To investigate the association between long-term exposure to air pollution and dementia and to assess the role of CVD in that association. Design, Setting, and Participants:Data for this cohort study were extracted from the ongoing Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a longitudinal population-based study with baseline assessments from March 21, 2001, through August 30, 2004. Of the 5111 randomly selected residents in the Kungsholmen district of Stockholm 60 years or older and living at home or in institutions, 521 were not eligible (eg, due to death before the start of the study or no contact information). Among the remaining 4590 individuals, 3363 (73.3%) were assessed. For the current analysis, 2927 participants who did not have dementia at baseline were examined, with follow-up to 2013 (mean [SD] follow-up time, 6.01?[2.56] years). Follow-up was completed February 18, 2013, and data were analyzed from June 26, 2018, through June 20, 2019. Exposures:Two major air pollutants (particulate matter ?2.5 ?m [PM2.5] and nitrogen oxide [NOx]) were assessed yearly from 1990, using dispersion models for outdoor levels at residential addresses. Main Outcomes and Measures:The hazard of dementia was estimated using Cox proportional hazards regression models. The potential of CVD (ie, atrial fibrillation, ischemic heart disease, heart failure, and stroke) to modify and mediate the association between long-term exposure to air pollution and dementia was tested using stratified analyses and generalized structural equation modeling. Results:At baseline, the mean (SD) age of the 2927 participants was 74.1 (10.7) years, and 1845 (63.0%) were female. Three hundred sixty-four participants with incident dementia were identified. The hazard of dementia increased by as much as 50% per interquartile range difference in mean pollutant levels during the previous 5 years at the residential address (hazard ratio [HR] for difference of 0.88 ?g/m3 PM2.5, 1.54 [95% CI, 1.33-1.78]; HR for difference of 8.35 ?g/m3 NOx, 1.14 [95% CI, 1.01-1.29]). Heart failure (HR for PM2.5, 1.93 [95% CI, 1.54-2.43]; HR for NOx, 1.43 [95% CI, 1.17-1.75]) and ischemic heart disease (HR for PM2.5, 1.67 [95% CI, 1.32-2.12]; HR for NOx, 1.36 [95% CI, 1.07-1.71]) enhanced the dementia risk, whereas stroke appeared to be the most important intermediate condition, explaining 49.4% of air pollution-related dementia cases. Conclusions and Relevance:This study found that long-term exposure to air pollution was associated with a higher risk of dementia. Heart failure and ischemic heart disease appeared to enhance the association between air pollution and dementia, whereas stroke seemed to be an important intermediate condition between the association of air pollution exposure with dementia.

Project description:IntroductionVulnerability to psychiatric manifestations is achieved by the influence of genetic and environment including stress and cannabis consumption. Here, we used a psychosocial stress model based on resident-intruder confrontations to study the brain corticostriatal-function, since deregulation of corticostriatal circuitries has been reported in many psychiatric disorders. CB1 receptors are widely expressed in the central nervous system and particularly, in both cortex and striatum brain structures.Aims and methodsThe investigation presented here is addressed to assess the impact of repeated stress following acute cannabinoid exposure on behavior and corticostriatal brain physiology by assessing mice behavior, the concentration of endocannabinoid and endocannabinoid-like molecules and changes in the transcriptome.ResultsStressed animals urinated frequently; showed exacerbated scratching activity, lower striatal N-arachidonylethanolamine (AEA) levels and higher cortical expression of cholinergic receptor nicotinic alpha 6. The cannabinoid agonist WIN55212.2 diminished locomotor activity while the inverse agonist increased the distance travelled in the center of the open field. Upon CB1 activation, N-oleoylethanolamide and N-palmitoylethanolamide, two AEA congeners that do not interact directly with cannabinoid receptors, were enhanced in the striatum. The co-administration with both cannabinoids induced an up-regulation of striatal FK506 binding protein 5. The inverse agonist in controls reversed the effects of WIN55212.2 on motor activity. When Rimonabant was injected under stress, the cortical levels of 2-arachidonoylglycerol were maximum. The agonist and the antagonist influenced the cortical expression of cholinergic receptor nicotinic alpha 6 and serotonin transporter neurotransmitter type 4 in opposite directions, while their co-administration tended to produce a null effect under stress.ConclusionsThe endocannabinoid system had a direct effect on serotoninergic neurotransmission and glucocorticoid signaling. Cholinergic receptor nicotinic alpha-6 was shown to be deregulated in response to stress and following synthetic cannabinoid drugs thus could confer vulnerability to cannabis addiction and psychosis. Targeting the receptors of endocannabinoids and endocannabinoid-like mediators might be a valuable option for treating stress-related neuropsychiatric symptoms.

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Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

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Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

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