Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk

BackgroundPost-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD.MethodsThe Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables.ResultsAt baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated.ConclusionPTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata

Characterization of glucocorticoid-induced loss of DNA methylation of the stress-response gene Fkbp5 in neuronal cells

Exposure to stress or glucocorticoids (GCs) is associated with epigenetic and transcriptional changes in genes that either mediate or are targets of GC signalling. FKBP5 (FK506 binding protein 5) is one such gene that also plays a central role in negative feedback regulation of GC signalling and several stress-related psychiatric disorders. In this study, we sought to examine how the mouse Fkbp5 gene is regulated in a neuronal context and identify requisite factors that can mediate the epigenetic sequelae of excess GC exposure. Mice treated with GCs were used to establish the widespread changes in DNA methylation (DNAm) and expression of Fkbp5 across four brain regions. Then two cell lines were used to test the persistence, decay, and functional significance of GC-induced methylation changes near two GC response elements (GREs) in the fifth intron of Fkbp5. We also tested the involvement of DNMT1, cell proliferation, and MeCP2 in mediating the effect of GCs on DNAm and gene activation. DNAm changes at some CpGs persist while others decay, and reduced methylation states are associated with a more robust transcriptional response. Importantly, the ability to undergo GC-induced DNAm loss is tied to DNMT1 function during cell division. Further, GC-induced DNAm loss is associated with reduced binding of MeCP2 at intron 5 and a physical interaction between the fifth intron and promoter of Fkbp5. Our results highlight several key factors at the Fkbp5 locus that may have important implications for GC- or stress-exposure during early stages of neurodevelopment

Individual and combined association between prenatal polysubstance exposure and childhood risk of attention-deficit/hyperactivity disorder.

IMPORTANCE: Polysubstance use among pregnant women has increased because of the opioid epidemic and the increasing legalization of cannabis along with persistent tobacco and alcohol consumption. Previous research on prenatal substance use and the child’s risk of attention-deficit/hyperactivity disorder (ADHD) has mostly focused on single-substance exposures; simultaneous examination of multiple substance use and assessment of their synergistic health consequences is needed. OBJECTIVES: To assess the consequences of the use of specific substances during pregnancy, investigate whether the interaction of multiple prenatal substance exposures is associated with increases in the risk of childhood ADHD, and estimate the aggregate burden of polysubstance exposure during gestation. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from the Boston Birth Cohort from 1998 to 2019. The sample of the present study comprised a multiethnic urban cohort of mother-child pairs who were predominantly low income. A total of 3138 children who were enrolled shortly after birth at Boston Medical Center were included and followed up from age 6 months to 21 years. EXPOSURES: Substance use during pregnancy was identified based on self-reported tobacco smoking, alcohol consumption, and use of cannabis, cocaine, or opioids in any trimester of pregnancy. Diagnostic codes for neonatal opioid withdrawal syndrome or neonatal abstinence syndrome from the International Classification of Diseases, Ninth Revision, and the International Classification of Diseases, Tenth Revision, were also used to identify opioid exposure during gestation. MAIN OUTCOMES AND MEASURES: ADHD diagnosis in the child’s electronic medical record. RESULTS: Among 3138 children (1583 boys [50.4%]; median age, 12 years [IQR, 9-14 years]; median follow-up, 10 years [IQR, 7-12 years]) in the final analytic sample, 486 (15.5%) had an ADHD diagnosis and 2652 (84.5%) were neurotypical. The median postnatal follow-up duration was 12 years (IQR, 9-14 years). Among mothers, 46 women (1.5%) self-identified as Asian (non–Pacific Islander), 701 (22.3%) as Hispanic, 1838 (58.6%) as non-Hispanic Black, 227 (7.2%) as non-Hispanic White, and 326 (10.4%) as other races and/or ethnicities (including American Indian or Indigenous, Cape Verdean, Pacific Islander, multiracial, other, or unknown). A total of 759 women (24.2%) reported the use of at least 1 substance during pregnancy, with tobacco being the most frequently reported (580 women [18.5%]). Cox proportional hazards models revealed that opioid exposure (60 children) had the highest adjusted hazard ratio (HR) for ADHD (2.19; 95% CI, 1.10-4.37). After including main statistical effects of all individual substances in an elastic net regression model, the HR of opioids was reduced to 1.60, and evidence of a statistical interaction between opioids and both cannabis and alcohol was found, producing 1.42 and 1.15 times higher risk of ADHD, respectively. The interaction between opioids and smoking was also associated with a higher risk of ADHD (HR, 1.17). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that it is important to consider prenatal concurrent exposure to multiple substances and their possible interactions when counseling women regarding substance use during pregnancy, the future risk of ADHD for their children, and strategies for cessation and treatment programs

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata

DataSheet_1_Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.docx

BackgroundPost-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD.MethodsThe Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables.ResultsAt baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated.ConclusionPTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.</p

Abstracts of Tanzania Health Summit 2020

This book contains the abstracts of the papers/posters presented at the Tanzania Health Summit 2020 (THS-2020) Organized by the Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender, and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); &amp; Tindwa Medical and Health Services (TMHS) held on 25–26 November 2020. The Tanzania Health Summit is the annual largest healthcare platform in Tanzania that attracts more than 1000 participants, national and international experts, from policymakers, health researchers, public health professionals, health insurers, medical doctors, nurses, pharmacists, private health investors, supply chain experts, and the civil society. During the three-day summit, stakeholders and decision-makers from every field in healthcare work together to find solutions to the country’s and regional health challenges and set the agenda for a healthier future. Summit Title: Tanzania Health SummitSummit Acronym: THS-2020Summit Date: 25–26 November 2020Summit Location: St. Gasper Hotel and Conference Centre in Dodoma, TanzaniaSummit Organizers: Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); &amp; Tindwa Medical and Health Services (TMHS)