1,721,346 research outputs found
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Posttraumatic Stress Disorder in Civilian Women: A Longitudinal Investigation on Cognition, Epigenetics, and Inflammation
No full textPost-traumatic stress disorder (PTSD) is a debilitating mental condition that develops in some individuals following exposure to traumatic events such as physical or sexual assault, combat, natural disasters, and accidents. The lifetime prevalence of PTSD is estimated to be 3.9% globally and 6.8% in the United States (US), and it is approximately twice as common in women than men.
A growing body of research has associated PTSD with various negative health outcomes, including cognitive impairments. However, much less is known about whether the elevated health risks persist after PTSD symptoms remit. In addition, more work is needed to elucidate the underlying mechanisms of how trauma-related distress becomes biologically embedded and subsequently leads to increased disease risks. One such mechanism is DNA methylation (DNAm), a widely-studied epigenetic modification that has shown great potential in tracing the long-term impact of environmental exposures and life experiences. Despite the increasing DNAm research on PTSD in civilian and female populations, longitudinal investigations of DNAm in PTSD have been limited to predominantly male military samples. Moreover, systematic chronic inflammation is another potential mechanism underlying PTSD that may also mediate the adverse impact of PTSD on subsequent health outcomes. However,
population studies have largely relied on assay-based measures of acute inflammatory biomarkers as proxies for chronic inflammation, and the fluctuating nature of these biomarkers may have contributed to inconsistent findings in PTSD-inflammation research. Recent studies indicate that DNAm may offer a more reliable measure of chronic inflammation, but no study has yet examined these DNAm-based proxies of inflammation in relation to PTSD.
This dissertation attempted to address these research gaps through a longitudinal investigation using data from trauma-exposed women in the Nurses' Health Study II, a large prospective cohort of nurses in the US. In Chapter 1, we examined PTSD symptom remission in relation to cognitive function and changes over time. We found that unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later, with accelerated cognitive decline observed among women with either unresolved or remitted moderate-severe PTSD symptoms. In Chapter 2, we performed epigenome-wide association analyses of lifetime PTSD diagnosis and symptom severity, utilizing blood samples collected twice over a decade apart. We identified 26 loci and 140 regions where DNAm level or changes were associated with PTSD. In Chapter 3, we examined multiple epigenetic signatures of C-reactive protein (CRP) and interleukin-6 (IL-6) based on published and newly-developed models. Our results showed that PTSD was associated with elevated levels of epigenetic signatures of CRP and a faster increase in these levels over time, as well as a suggestive association between PTSD and increased epigenetic IL-6 levels.
These findings highlight the importance of monitoring cognitive function and inflammation in women with PTSD and advance our understanding of the biological pathways underlying PTSD pathophysiology
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War-Related Trauma and Psychosocial Health in South Sudan and Liberia
No full textThe study of psychological trauma in humanitarian settings has consistently revealed the negative mental health impact of exposure to war atrocities, especially high rates of post-traumatic stress disorder. However, there is little consensus on what is meant by war trauma, how it should be measured, how ‘levels’ of trauma vary across sociodemographic groups, what individual narratives tell us about culture-specific conceptualizations of trauma, and how this trauma interacts with other factors to influence long-term risk and resilience. The conceptualization, measurement, and impact of war trauma remains a critical area of scientific inquiry, especially given the growing research on the mental health of war-affected populations globally. Moreover, studies on trauma and mental health with conflict-affected populations have mostly employed measurement tools developed in the West, and thus may not accurately reflect the cultural norms of the specific population they were targeting. There is thus an urgent need to incorporate culturally validated tools to understand the war atrocities that people experience, witness, and perpetuate, so that psychosocial services can be appropriately designed.
This dissertation uses mixed-methods to examine war-related trauma in internally displaced civilians and combatants in two African countries that are in different stages of post-conflict rehabilitation and recovery: Liberia and South Sudan. Overall, the findings highlight the role of robust measurement research and the cultural richness of qualitative research in contextualizing war-related adversities and their impact. Specifically, Paper 1 uses psychometric analyses to understand how trauma expression is manifested across men and women in South Sudan, and make recommendations for the use of survey measures in global health. Paper 2 uses structural equation modeling to study the complex relations between ethnicity, gender, combat stress, trauma, post-traumatic stress disorder, and perceived security in South Sudan. Paper 3 uses qualitative thematic analysis to understand the long-term determinants of risk and resilience in adults exposed to armed violence in post-conflict Liberia. This dissertation aims to provide the first critical step in the design of appropriate measures and targeted psychosocial interventions in these conflict-affected settings, with the goal of helping policymakers incorporate local priorities into national programs.Trauma; PTSD; South Sudan; Liberia; Conflict; Mixed-method
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The Relation Between Age at Immigration and Mental Health
No full textImmigrants in the United States are a growing population, but little is known about how their mental health may vary by their age at immigration.
In Chapter 1, we used logistic regression to estimate the odds of incident depression and anxiety in a large, nationally-representative sample of US adults. We found those who immigrated between ages 0-5 years old (early-childhood) were more likely than those born in the US to develop depression and anxiety, while those who immigrated during adolescence or later were less likely to develop depression and anxiety.
In Chapter 2, we used Poisson regression to estimate the effect of childhood adversities on the risk for depression and anxiety in a large sample of immigrants. We also estimated and decomposed the joint effects of childhood adversities and age at immigration into components due to the effect of childhood adversities alone, the effect due to age at immigration alone, and the effect due to their interaction. We found that childhood adversities significantly interacted with age at immigration such that those with the greatest risk were those who immigrated during early-childhood and had exposure to childhood adversities. When the joint effects of childhood adversities and age at immigration were decomposed, the effect of age at immigration alone was consistently greater than that of childhood adversities alone across all adversities. While synergistic effects were present for both depression and anxiety, antagonistic effects between childhood adversities and age at immigration were only present for depression.
In Chapter 3, we estimated the prevalence of mental treatment by age at immigration in a large, nationally-representative sample of US adults who were prevalent with depression or anxiety and compared the usage of different treatment modalities between immigrants and non-immigrants. We found that those who immigrated during early-childhood had similar, and at times higher, treatment use that those born in the US. Those who immigrated after early-childhood had consistently lower treatment use than those born in the US. We also found that fewer immigrants across all ages at immigration were prescribed medication for their symptoms and more immigrants visited the emergency room for their symptoms.Immigration; age at immigration; mental health; depression; anxiety; mental health treatmen
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Untangling the risk of onset and persistence of PTSD and Depression following Traumatic Events
No full textTraumatic events are a common part of the human experience. Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are common sequelae of trauma that are both associated with poor physical health and mortality. The objective of this dissertation is to identify common and unique risk factors for each disorder in order to identify at-risk groups for PTSD and/or depression following trauma.
his dissertation is organized into five parts: 1) an introduction, 2) a simulation study exploring the use of test equating methods to standardize the Hospital Anxiety and Depression Scale (HADS) to the Beck Depression Inventory II (BDI) in order to create common depression scale across studies in a pooled analysis, 3) an individual participant data meta-analysis on risk factors for PTSD and depression following incident trauma, 4) a Mendelian Randomization analysis of childhood abuse victimization and neuroticism on PTSD and depression, 5) a discussion of the findings and avenues for future research.
The simulation study found that an Equated BDI diagnosis had higher specificity (range: 0.86 to 0.91) compared to using the HADS diagnosis (range: 0.80 to 0.82) when the correlation between the BDI and HADS was greater than 0.7, but had lower sensitivity (Equated BDI range: 0.67 to 0.72; HADS range: 0.84 to 0.92). The Equated BDI diagnosis was found to improve statistical power when the prevalence of depression was 20% or higher with greater improvements when the proportion of studies assessing the depression with the HADS was less than 50%.
In the individual participant data meta-analysis, common risk factors for acute and persistent MDD and PTSD were found including increased risk for female sex and reduced risk for those who experienced an accident versus an assault or other traumatic event as the index trauma. Acute MDD symptom severity was associated with persistent PTSD and remained significant after inclusion of acute PTSD symptom severity. In an analysis of PTSD symptom clusters, only reexperiencing symptoms were associated with persistent PTSD along with MDD symptom severity. In models of persistent MDD, acute PTSD symptom severity was associated with persistence, but neither overall symptom severity nor cluster symptom severities were associated with persistence after inclusion of acute MDD symptom severity. In the Mendelian Randomization analysis, childhood abuse victimization was found to be associated with PTSD symptom severity but was not associated with an increased odds of a MDD diagnosis, while neuroticism was associated with an increased odds of a diagnosis of MDD, but was not associated with an increase in PTSD symptom severity.
Findings from the meta-analysis that leveraged the use of item-response theory imply that while PTSD and MDD share many risk factors for onset of symptoms following the experience of a traumatic event, persistence of symptoms depends most strongly on initial symptoms. However, PTSD and MDD were also found to have different relationships with childhood abuse victimization and neuroticism, indicating that some risk factors are unique to each disorder. Future studies can build upon these results, especially when pooling data from different studies, to further explicate the associations between PTSD, MDD, and their causes
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Childhood Origins of Cardiometabolic Disease: Psychosocial Predictors of Risk and Resilience
No full textA growing body of work suggests that the roots of cardiometabolic health may trace back to the first decades of life, with positive and negative early experiences setting the stage for health in adulthood. While prior research has examined psychosocial pathways of risk and resilience in relation to adult cardiometabolic outcomes, no studies have assessed their impact on health and well-being earlier in the life course. Therefore, this dissertation investigates whether these pathways might begin to show effects on health as early as childhood and adolescence.
Paper 1 uses data from the Avon Longitudinal Study of Parents and Children to examine whether children with higher versus lower levels of positive psychological and behavioral assets are more likely to be in optimal cardiometabolic health by age 17 years. Results indicated that childhood assets cumulatively predicted cardiometabolic health by adolescence, with impacts observed across multiple physiologic systems. Paper 2 assesses whether poor mental health at age 5 years contributes to declines in cardiometabolic functioning from early to middle childhood using data from the Generation R Study. Although mental health did not appear to be associated with cardiometabolic functioning in early childhood, findings indicated that higher levels of mental health problems predicted declines in cardiometabolic functioning by age 9 years. Finally, Paper 3 uses data from the Generation R Study to investigate associations of ethnic-based intergroup threat reported by mothers with children’s mental health to identify intergenerational pathways of risk that likely precede emotion-related alterations in cardiometabolic functioning. Results found evidence of adverse intergenerational effects on mental health among children whose mothers experienced a strong sense of intergroup threat, irrespective of ethnic minority status.
The three studies in this dissertation indicate that psychosocial factors can influence pathways of cardiometabolic risk and resilience in ways that are evident prior to adulthood. Therefore, it is possible that the health benefits of childhood assets and the deteriorative effects of poor mental health may contribute to previously documented associations between psychosocial factors in childhood and adult health outcomes. Taken together, these studies highlight potential new targets for childhood intervention that may help delay the onset of chronic disease or prevent it altogether.Social and Behavioral Science
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Social Adversities and Inequities in Psychosis
No full textEthnic minorities have higher risk of psychotic disorders such as schizophrenia. Available evidence indicates that social adversities such as discrimination and parental loss play a role in this increased risk. This dissertation takes a multi-method approach to: 1) quantitatively investigate whether two social adversities, major discrimination and early parental death, help explain excess risk of psychotic disorders among ethnic minorities, and 2) qualitatively describe how individuals with psychotic disorders perceive the role of social adversities in their illness. Quantitative analyses used the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions population-based case-control study from 16 catchment sites across six countries. Multivariable mixed-effects logistic regression models were used to estimate the associations between discrimination and psychosis and parental death and psychosis. Stratified analyses were used to explore differences by ethnic minority status. Qualitative analyses used 20 semi-structured, in-depth interviews of patients with psychotic disorders receiving treatment at an outpatient psychiatric clinic. Modified Grounded Theory was used to understand how early social adversities influenced later family interactions. Experiencing pervasive discrimination was three times more common among ethnic minorities than the ethnic majority, and associated with 1.8-fold greater odds of psychosis compared to those with no discrimination. When stratified, this association held for ethnic minorities but not the ethnic majority. Experiencing early parental death was twice as common among ethnic minorities than the ethnic majority. Individuals who experienced early maternal death had 2.3-fold greater odds and those who experienced multiple early parental deaths had 4.4-fold greater odds of psychosis compared to those with no early parental death. When stratified, ethnic minorities had a much stronger association for multiple deaths than the ethnic majority. Qualitatively, patients with psychotic disorders who described early adversities of childhood abuse and/or unstable homes tended to explicitly link these experiences to limited family interactions, including perceived absence of support for their illness. This differed from patients who did not mention early adversities and described positive family interactions and perceived supportive involvement in their illness. These findings advance our understanding of the role of social adversities in psychosis, including helping to explain the excess risk among ethnic minorities.Social and Behavioral Science
The Associations of Posttraumatic Stress Disorder with Secondary Mental and Physical Health Disorders
No full textGene-Environment Interactions and Depression
Full text linkPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64289/1/Koenen_Gene Environment_2009.pd
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Understanding Peripheral Biological Variability in Posttraumatic Stress Disorder: Omics and Causal Approaches
No full textPosttraumatic stress disorder (PTSD) is the quintessential trauma-related psychiatric disorder that profoundly impacts long-term health. A growing body of literature links PTSD to elevated risks for cardiometabolic diseases and premature mortality, with stress-activated biological processes in both central and peripheral systems discussed as potential mechanisms. Recent studies assessing associations between PTSD and biological differences in markers obtained from peripheral tissues (e.g., inflammatory markers) have highlighted promising directions for improving our understanding of PTSD pathophysiology and health consequences. However, current knowledge remains limited regarding the relevance of different types of biological data and the utility of various methodological approaches. This dissertation examines links between PTSD symptoms and three types of biological data derived from peripheral blood samples: metabolomics, DNA methylation (DNAm), and triglycerides. Applying novel approaches in our investigations, we aimed to improve the characterization of PTSD-related biological differences and explore their implications for long-term health.
In Chapter 1, we pursued the first large-scale, population-based metabolome-wide investigation of PTSD, using plasma metabolomics data from three subsamples (total N=2,835 women) nested within the Nurses’ Health Study II (NHSII). Building on prior metabolomic analyses of depression and anxiety, our results revealed shared and distinct metabolic alterations linked to PTSD versus depression or anxiety. Notably, we identified 29 metabolites (primarily elevated glycerophospholipids and glycerolipids) associated with persistent PTSD symptoms but not with remitted PTSD. Our findings highlight the considerable metabolic impact of chronic, non-remitted PTSD symptoms and provide insights into mechanisms that may underlie elevated cardiometabolic disease risk in individuals experiencing PTSD symptoms.
In Chapter 2, we offered a proof-of-principle for using DNA methylation data from peripheral blood samples to identify subtypes of trauma-exposed civilians with meaningful differences in PTSD symptoms and health. Exploratory analyses were performed in a subsample of women in NHSII (N=707), with external validation in the Detroit Neighborhood Health Study (N=324), a longitudinal cohort of predominantly non-Hispanic African American men and women. While specific subtype classifications remain preliminary, our study demonstrated that peripheral DNAm profiles may capture both short-term and long-term information about PTSD symptom severity and physical health. This work supports the utility of a multivariate approach linking biological variation to symptom and health heterogeneity.
In Chapter 3, we examined the bidirectional relationship between PTSD and circulating triglycerides, triangulating evidence from a summary data-based two-sample Mendelian randomization study and observational analyses in NHSII. Our findings supported an effect of PTSD on elevated triglyceride levels, whereas the impact of triglycerides on PTSD risk appeared limited. By carefully considering potential biases in each design and performing a series of sensitivity analyses to address these concerns, this study improved our understanding of the causal relationship between PTSD and triglycerides.
Taken together, findings from these three studies highlight the importance of understanding peripheral biological differences linked to trauma and PTSD. Both broad, hypothesis-generating strategies and focused, hypothesis-testing investigations can offer valuable insights. A key direction for future work is to assess the extent to which these biological differences may mediate long-term health risks related to PTSD.Population Health Science
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