Life Stressor Checklist-Revised Research Articles

Adverse Childhood Experiences and Adult Mental Health Outcomes

Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

Adverse Childhood Experiences and Higher Levels of Stress Are Associated With the Co-occurrence of Cancer-Related Cognitive Impairment and Anxiety

We sought to identify subgroups of patients with distinct joint cancer-related cognitive impairment (CRCI) AND anxiety profiles and evaluate for differences in demographic and clinical characteristics, as well as levels of global stress, cancer-specific stress, cumulative life stress, and resilience. Patients (n = 1332) completed the Attentional Function Index and the Spielberger State Anxiety Inventory six times over two cycles of chemotherapy. Global, cancer-specific, and cumulative life stress and resilience were evaluated using Perceived Stress Scale, Impact of Event Scale-Revised, Life Stressor Checklist-Revised, and Connor-Davidson Resilience Scale, respectively. Latent profile analysis was used to identify subgroups of patients with distinct joint CRCI AND anxiety profiles. Differences were evaluated using parametric and nonparametric tests. Three classes were identified (ie, No CRCI and Low Anxiety [57.3%], Moderate CRCI and Moderate Anxiety [34.5%], and High CRCI and High Anxiety [8.2%]). All of the stress measures showed a dose-response effect (ie, as the CRCI AND anxiety profile worsened, scores for all three types of stress increased). The two highest symptom classes reported higher occurrence rates for six specific stressors (eg, emotional abuse, physical abuse, sexual harassment). Findings suggest that higher levels of co-occurring CRCI AND anxiety are associated with some common risk factors, as well as higher levels of stress and lower levels of resilience. Increased knowledge of modifiable risk factors and sources of stress associated with the co-occurrence of these two symptoms will assist clinicians to identify high-risk patients and implement individualized interventions.

Maternal steroids during pregnancy and their associations with exposure to lifetime stressful life events, prenatal stress appraisal and psychological functioning

BackgroundDuring pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied. AimTo assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22–40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334). MethodsSerum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects. ResultsHigh prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [β (95%CI): androgens: −0.13 (−0.25;−0.01); estrogens: −0.16 (−0.31;−0.01)], particularly among women carrying males [androgens: −0.22 (−0.39;−0.05); estrogens: −0.28 (−0.50;−0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite—5alpha-androstan-3alpha,17alpha-diol disulfate—negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males. ConclusionsIncreased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.

Various types of stress and greater use of disengagement coping are associated with worse sleep disturbance in oncology patients undergoing chemotherapy.

Various types of stress and the choice of coping strategies may be risk factors for higher levels of sleep disturbance in oncology patients. Purposes were to evaluate for differences in global, cancer-specific, and cumulative life stress, as well as resilience and the use of coping strategies among three subgroups of patients with distinct sleep disturbance profiles (i.e., Low, High, Very High). Oncology outpatients (n=1331) completed measures of global (Perceived Stress Scale), cancer-specific (Impact of Event Scale-Revised), and cumulative life (Life Stressor Checklist-Revised) stress, resilience (Connor-Davidson Resilience Scale) and coping (Brief Cope) prior to their second or third cycle of chemotherapy. Sleep disturbance was assessed six times over two chemotherapy cycles. Differences were evaluated using parametric and non-parametric tests. All stress measures showed a dose response effect (i.e., as the sleep disturbance profile worsened, levels of all types of stress increased). Compared to Low class, the other two classes reported higher levels of global perceived stress and higher occurrence rates and effect from previous stressful life events. Impact of Event Scale-Revised scores for the Very High class indicated post-traumatic symptomatology. Patients in High and Very High classes had resilience scores below the normative score for the United States population and used a higher number of disengagement coping strategies. Our findings suggest that very high levels of sleep disturbance are associated with higher levels of various types of stress, lower levels of resilience, and higher use of disengagement coping strategies. Clinicians need to perform routine assessments and implement symptom management interventions to reduce stress and encourage the use of engagement coping strategies.

Full-scale military invasion of the Russian Federation of Ukraine as a factor of social transformations in higher education

The aim of the research is to study social transformations in the field of higher education under the impact of the factor of military invasion. Methods: The method of expert evaluations; Testing and questionnaire survey using the following methods: Life Stressor Checklist–Revised (LSC-R), Organizational Culture Assessment Instrument (OCAI). Analysis of statistics was carried out using t-Student, φ-Fisher tests; multidimensional methods of data analysis (regression, factor, correlation). The results: The study showed that the average indicator for the sample is in the range of high values (M = 518 ± 604). In general, neuro-psychological tension (NT) in the aggregate sample is in the medium range (M=58.4±7.32). The results demonstrate a typologically pronounced level of trust as a psychological phenomenon among students in the wartime (Trust Index: M=98.3±5.27). Conclusions: The results of the study showed a significant impact of the hostilities on the social transformations of the educational sector. This is due to changes in organizational needs and psychological stress. Prospects: Further research should be aimed at studying the driving forces of social transformation in the wartime. It is also necessary to develop a methodological framework for monitoring and evaluating such changes.

Maternal Stress and Human Milk Antibodies During the COVID-19 Pandemic.

ImportanceSARS-CoV-2-specific antibodies in human milk might protect the breastfed infant against COVID-19. One of the factors that may influence human milk antibodies is psychological stress, which is suggested to be increased in lactating women during the COVID-19 pandemic.ObjectiveTo determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of SARS-CoV-2-specific antibodies in human milk.DesignPopulation-based prospective cohort study.SettingData collection took place in the Netherlands between October 2020 and February 2021.ParticipantsLactating women living in the Netherlands were eligible to participate in this study. In total, 2310 women were included.ExposuresStress exposure during the COVID-19 pandemic was determined using the Perceived Stress Scale (PSS) questionnaire and maternal lifetime stress was determined by the Life Stressor Checklist – revised (LSC-r) questionnaire.Main Outcome(s) and Measure(s)Stress experience during the COVID-19 pandemic was compared with a pre-pandemic cohort. SARS-CoV-2-specific antibodies in human milk were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) with the Spike protein of SARS-CoV-2. The association between maternal stress and human milk antibodies was determined using a multiple regression model.ResultsThe PSS score of lactating mothers was not increased during the pandemic compared to the PSS score in the prepandemic cohort. Six hundred ninety-one participants had SARS-CoV-2-specific antibodies and were included in the regression models to assess the association between maternal stress and human milk antibodies. No association was found between PSS scores and human milk antibodies. In contrast, the LSC-r score was negatively associated with SARS-CoV-2-specific IgA in human milk (β = 0.98, 95% CI: 0.96–0.997, p = 0.03).Conclusions and RelevanceOur results suggest that lactating women in the Netherlands did not experience higher stress levels during the COVID-19 pandemic. Breastfed infants of mothers with high chronic stress levels receive lower amounts of antibodies through human milk, which possibly makes them more vulnerable to respiratory infections. This emphasizes the importance of psychological wellbeing during lactation.

Posttraumatic stress disorder symptom severity is associated with reduced Montreal Cognitive Assessment scores in a sample of Vietnam War Veterans.

The goal of the present study was to examine associations between posttraumatic stress disorder (PTSD) symptom severity, the number of stressors experienced, and cognitive outcomes in a sample of U.S. Vietnam War Veterans (N = 274). Adults between 60 and 85 years of age completed a Vietnam Veterans Alzheimer's Disease Neuroimaging Initiative Project visit. A modified version of the Life Stressor Checklist-Revised (LSC-R) was used to assess the number of stressful experiences participants experienced, current PTSD severity scores were measured via the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Linear regressions were conducted to examine the effect of CAPS-IV and LSC-R scores on cognitive performance. Higher CAPS-IV scores were associated with worse cognitive outcomes on the MoCA, ΔF(1, 264) = 12.686, p < .001, R2 = .142. In contrast, the number of reported stressful experiences was not associated with cognitive outcomes. After accounting for multiple comparisons, findings indicated that CAPS-IV severity scores were significantly associated with the MoCA memory index. In a sample of older Veterans, PTSD symptom severity, but not the number of reported stressors, was associated with poorer performance on a well-established cognitive function screening tool. Analyses of specific MoCA domains indicated that memory may be driving this association. These findings suggest that highly arousing stressors characteristic of PTSD, rather than stressful experiences more broadly, contribute to this association. Future work can use these findings to explore whether treating PTSD symptoms may help maintain cognitive function during the aging process.

Serious financial difficulties, psychological stress, and subclinical cardiovascular disease in Mexican women

PurposeTo investigate the association between serious financial difficulties (SFD), stress, and cardiovascular health in women. MethodsWe categorized 1759 employed and insured disease-free women from the Mexican Teachers’ Cohort according to their response to a question on SFD included in the Life Stressor Checklist-Revised administered in 2012 and 2016. We also measured perceived stress (n = 1598) and hair cortisol levels (n = 539) in study participants. Carotid intima-media thickness was measured, and carotid atherosclerosis determined in all participants. ResultsMultivariable regression models indicated that women exposed to SFD had 1.6% (95% CI: 0.05, 3.2) higher mean intima-media thickness and 1.37 (95% CI: 1.02, 1.85) higher odds of carotid atherosclerosis relative to women without SFD. The magnitude of the observed associations was higher in women reporting longer duration of the event and higher emotional burden. Mediation analyses suggested a potential role of perceived stress and body mass index in these associations. Cortisol levels did not differ between groups. ConclusionsSFD was associated with subclinical cardiovascular disease among employed and insured women. Limiting stress and adiposity may be potential targets for interventions.

Subjective perception of life stress events affects long-term pain: the role of resilience

ObjectiveThere is evidence that experiencing childhood trauma and life stressors across the lifespan together with lower resilience is associated with chronic pain-related conditions. The aim of this study was to explore the potential mediating role of resilience in the relationship between childhood trauma and long-term pain and to explore a possible moderating role of serious life stressors in the last year.MethodsThe participants, drawn from a representative sample of citizens of the Czech Republic (n = 1800, mean age: 46.6 years, 48.7% male), were asked to report various long-term pain conditions, childhood trauma (Childhood Trauma Questionnaire, CTQ), life stressors (Life Stressor Checklist Revised, LSC-R) and resilience (Brief Resilience Scale, BRS) in a cross-sectional face-to-face study conducted in 2016. A conditional process SEM model of moderated mediation was performed.ResultsThe occurrence of life stress events affecting the participant’s last year moderated the relationship between childhood trauma, resilience and health. In the group of participants who experienced at least one life stress event affecting their last year, resilience fully mediated the effect of past childhood trauma on long-term pain. In participants who did not experience life stressors with an impact on the last year, the direct path from childhood trauma to health through resilience lost its significance.ConclusionThe subjective meaning of stress events on one’s life has an impact on the trajectory between childhood trauma and health and acts as a moderator. Resilience may buffer the negative effect of trauma on later long-term pain.

Lifetime exposure to violence and other life stressors and hair cortisol concentration in women

Women are exposed to a variety of life stressors, particularly violence, during their lifetime which increases the risk of developing various psychiatric and somatic diseases, with the dysregulated secretion of cortisol as one potential biological mechanism. We examined the association between violence and other life stressors and hair cortisol concentration (HCC) in a population of urban women. We included 470 adult women (age = 21–86 years) attending the Cancer Detection Clinic in Iceland. The Life Stressor Checklist-Revised (LSC-R; 30-items) was used to assess exposure. HCC was measured with liquid chromatography coupled with tandem mass spectrometry. We used linear regression models to assess the association between life stressors and log-transformed HCC. The median HCC (pg/mg) in the study population was 4.9 (range 0.6–616.6). HCC was not associated with background covariates, including age (p = 0.868), education level (p = 0.824), marital status (p = 0.545), income (p = 0.363), occupation (p = 0.192), but associated with current smoking (p = 0.013). We noted a 3.3% (95% CI: 0.17–6.6%) associated increase in HCC per endorsed life stressor after adjusting for age and smoking, while non-violent life stressors were not associated with HCC. Per endorsed violence item, we observed a 10.2% (95% CI: 1.4–19.7%) associated increase in HCC after age and smoking adjustment. Women with lifetime exposure to both physical and sexual violence presented with higher HCC than unexposed women (p = 0.010), after age and smoking adjustment. Lifetime exposure to violence was associated with higher levels of HCC in a community sample of women. These findings need confirmation with prospective studies.

Life Stressors in Patients with Inflammatory Bowel Disease: Comparison with a Population-Based Healthy Control Group in the Czech Republic.

Background: Stress has been suggested to play a potential role in inflammatory bowel disease (IBD) pathogenesis, but studies focussing on the occurrence of specific life stress events among IBD patients are scarce. Therefore, the aim of the present study was to explore the association between various life stress events and IBD. Methods: Patients with IBD (N = 98, mean age: 38.45, 54.1% men) were compared to a group of healthy controls (N = 405, mean age: 36.45, 58.0% men) originating from a health survey conducted on a representative population sample of Czech adults. The Life Stressor Checklist-Revised (LSC-R) was used to assess the stressors. Results: IBD patients had higher odds of reporting life stressors overall (p < 0.001), life stressors before the age of 16 (p < 0.004) and a higher score in traumatic stress (p < 0.005) and interpersonal violence (p < 0.001) when compared to the control group. Gender- and diagnosis-related differences are discussed. Conclusion: Reporting life stressors experienced during childhood or adulthood is strongly associated with IBD. This should be considered in illness management, especially in a severe course of IBD.

Associations of Maternal Trait Anger Expression and Lifetime Traumatic and Non-traumatic Experiences with Preterm Birth.

Most studies examining psychosocial factors contributing to preterm birth (PTB) have focused on negative life events. Studies examining the influence of negative emotion, in particular maternal anger, remain sparse. We examined associations of maternal trait anger expression and lifetime traumatic and non-traumatic experiences with the risk of PTB. Mother-newborn pairs were enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based in Boston and New York City. Women completed the State-Trait Anger Expression Inventory-2 (STAXI-2), Life Stressor Checklist-Revised (LSC-R), and Childhood Trauma Questionnaire (CTQ) in pregnancy. We used modified Poisson regression to estimate the relative risk (RR) of PTB (1) in relation to continuous STAXI-2 Anger Expression-In (AX-I) and Anger Expression-Out (AX-O) subscales, (2) in relation to continuous LSC-R scores, and (3) between women who did versus did not experience childhood sexual, emotional, and/or physical abuse in six separate models. We also examined interactions between maternal anger expression and lifetime stress/childhood trauma. Younger, single, minority women had higher outward anger expression and inward anger suppression. AX-I and AX-O scores were higher among women who experienced abuse in childhood and who had higher lifetime stress. Maternal lifetime stress, outward anger expression, and inward anger suppression were associated with an increased risk of PTB in separate models; however, stress, trauma and anger did not interact to further increase the risk of PTB. CONCLUSIONSFOR PRACTICE: Higher anger expression and higher lifetime stress experiences were associated with an increased risk of PTB among a racially and ethnically diverse sample of pregnant women.

Disentangling Associations Among Maternal Lifetime and Prenatal Stress, Psychological Functioning During Pregnancy, Maternal Race/Ethnicity, and Infant Negative Affectivity at Age 6 Months: A Mixtures Approach.

Purpose: Maternal stress and psychological dysfunction in pregnancy are independently linked with fetal neurodevelopment. Stress encompasses environmental stressors and psychological and physiological responses. Stressors and psychopathology co-occur with patterns differing by race/ethnicity. We aimed to extend environmental mixtures methodology to elucidate prenatal stress associations with infant negative affectivity (NA) in a racially/ethnically mixed cohort.Methods: Participants were mother/infant dyads (n=445) in a prospective pregnancy cohort study in two urban US settings in 2011–2018. During pregnancy, women completed the Life Stressor Checklist-Revised, Crisis in Family Systems-Revised, Edinburgh Postnatal Depression Scale, and post-traumatic stress disorder (PTSD) Checklist-Civilian version; the Infant Behavior Questionnaire-Revised assessed NA in 6-month olds. Using weighted quantile sum (WQS) regression, we developed a weighted maternal stress index encompassing lifetime and current life events and symptoms of depression and PTSD. Stress-by-race/ethnicity interactions allowed differential contributions of individual stress domains by maternal race/ethnicity.Results: Mothers were majority black (44%) or Hispanic (37%). Stress questionnaire and infant NA scores were similar by race/ethnicity. The WQS prenatal stress score was positively associated with infant NA (β: 0.40 [95% confidence interval 0.16–0.64]). PTSD was the strongest contributor to the WQS score in Hispanic women (59%), whereas in black women, lifetime stress and depressive symptoms accounted for 38% and 35%, respectively, of the association with NA.Conclusions: Extending environmental mixtures methodology to stress research may disentangle complex associations among lifetime and current stressful life events and psychological symptomatology and their contributions to early childhood neurobehavioral outcomes. Consideration of effect modification by race/ethnicity may inform understanding of differing vulnerability across racial/ethnic groups.

Cumulative lifetime maternal stress and stress in pregnancy are differentially associated with extracellular vesicle encapsulated microRNA profiles in breast milk: Findings from the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy coho

Background/Aims: While maternal stress has been linked to adverse child health outcomes, mechanistic links have not been fully elucidated. Maternal microRNAs encapsulated in Extracellular Vesicles (EVs) reach the infant through breastmilk and are a novel biochemical communication pathway for early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Methods: We assessed maternal lifetime stress using the Life Stressor Checklist-Revised (LSCR) survey and negative life events (NLEs) experienced in the past 6 months during pregnancy using the Crisis in Family Systems-Revised (CRISYS-R) survey. Extracellular vesicles were isolated from N=80 breastmilk samples collected at 6.1±5.9 weeks postnatally. Total RNA was extracted and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Logistic regression assessed associations between continuous LSCR and NLE scores and EV-microRNA detection (outcome yes/no);associations with EV-microRNA expression levels were assessed using robust linear regression (N=74 with EV-microRNA and maternal stress data). Models were adjusted for infant sex, maternal race/ethnicity, education, and week of breast milk collection. Results: Among 345 EV-microRNAs detected in &gt;10% of samples, detection of 127 (47%) was associated with LSCR score and detection of 97 (28%) was associated with NLE score (p &lt; 0.05). Among 205 EV-microRNAs detected in &gt;50% of samples, expression of 8 was associated with LSCR scores and expression of 17 was associated with NLE score at our a priori criteria of p &lt; 0.05 and |Bregression| &gt; 0.2. MicroRNAs associated with LSCR and NLE scores were involved in KEGG pathways related to fatty acid metabolism and steroid biosynthesis. Conclusions: Maternal lifetime cumulative stress and stress during pregnancy were associated with EV-microRNAs in breast milk although microRNA profiles differed. Further research is needed to identify biological pathways impacted by differentially expressed microRNAs and investigate relationships with child health outcomes.

Longitudinal study of PTSD and depression in a war-exposed sample – comorbidity increases distress and suicide risk

Background Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are the most common mental disorders following traumatic experiences. The aim of this study was to investigate the extent to which PTSD and depression co-occurred in Serbian general population at baseline and 1 year after the follow-up, as well as how this co-occurrence was associated with sociodemographic factors, personal distress, suicidality and quality of life. Subjects and methods The sample consisted of 159 subjects, who fulfilled the IES criteria for PTSD, and were taken from a larger sample of 640 participants, which was chosen by a random walk technique in five regions of the country affected by major trauma. The assessment was carried out by the following instruments: Mini International Neuropsychiatric Interview 5 (MINI 5), Life Stressor Checklist-Revised (BSC-R), Brief Symptom Inventory (BSI), Impact of Event Scale-Revised (IES-R) and Manchester Short Assessment of Quality of Life Scale (MANSA). The follow-up study was carried out 1 year after the baseline. Results In the initial phase, PTSD was found in 100 out of 159 participants (62.9%), while 81 (51%) fulfilled the diagnostic criteria for MDD. Comorbidity of PTSD and depression was identified in 65 (40.9%) subjects of the sample. After 1 year, PTSD was found in 56 (35.2%) and MDD in 73 (45.9%) participants. Comorbidity of PTSD and depression in the follow-up phase was identified in 41 (25.8%) subjects of the sample. The subjects with comorbidity had significantly higher level of post-traumatic stress symptoms, general psychological distress as well as suicide risk and lower level of quality of life than participants with either condition alone. Conclusion PTSD–depression comorbidity is a common post-traumatic condition. Complex psychopathology, severity of symptoms and their consequences, both at individual and community levels, require attention to be paid to early diagnostics and treatment of affected persons.

Associations Between Maternal Lifetime Stress and Placental Mitochondrial DNA Mutations in an Urban Multiethnic Cohort

BackgroundDisrupted placental functioning due to stress can have lifelong implications. Cumulative stress and trauma are likely to have lasting impacts on maternal physiological functioning and offspring development, resulting in increased risk for later-life complex disorders for which racial disparities exist. MethodsThis study examined the association between maternal lifetime stress and placental mitochondrial DNA mutational load in an urban multiethnic cohort. Maternal lifetime exposure to stressful events was assessed using the validated Life Stressor Checklist–Revised. Whole mitochondrial DNA sequencing was performed and mutations were determined for 365 placenta samples with complete exposure and covariate data. Multivariable regression was used to model maternal lifetime stress in relation to placental mitochondrial DNA mutational load. Racial/ethnic differences were examined by cross-product terms and contrast statements. Gene-wise analyses were conducted. ResultsWe identified 13,189 heteroplasmies (Phred score > 10,000, minor allele frequency < 0.5, number of mutant reads > 1). Women experiencing increased psychosocial stress over their lifetime exhibited a higher number of total placental mitochondrial mutations (β = .23, 95% confidence interval = .03 to .42) and heteroplasmic mutations (β = .18, 95% confidence interval = .05 to .31) but not homoplasmic mutations (β = −.008, 95% confidence interval = −.03 to .01); the strongest associations were observed among Black women and genes coding for NADH dehydrogenase and cytochrome c oxidase subunits. ConclusionsCumulative maternal lifetime stress is associated with a greater mitochondrial mutational load, particularly among Black women. The impact of racial/ethnic differences in mutational load on placental function directly affecting offspring development and/or leading to chronic disease disparities warrants further investigation.

A-015 Posttraumatic Stress Disorder Symptoms are Associated with Reduced Performance on the MoCA among Vietnam Veterans

Abstract Objective To examine cross-sectional associations between posttraumatic stress disorder (PTSD) symptom severity, number of stressors experienced, and cognitive outcomes in Vietnam War veterans. Methods 366 adults between the ages of 60–85 years old completed a Vietnam Veterans Alzheimer’s Disease Neuroimaging Initiative Project (ADNI-DoD) visit consisting of a clinical interview and neuropsychological assessment. Number of stressful experiences were measured with the Life Stressor Checklist-Revised (LSC-R). Severity scores were assessed via the current Clinician-Administered PTSD Scale (CAPS). Correlations were conducted between selected measures of stress and age, years of education, sex, ethnicity, and race. Demographic variables with significant associations with stress were included as covariates in the hierarchical regressions. Hierarchical linear regressions were conducted to examine the effect of CAPS and LSC-R on baseline Montreal Cognitive Assessment (MoCA) scores. Results Higher CAPS scores (indicating higher PTSD severity) were associated with worse cognitive outcomes on the MoCA [ΔF(1,269) = 15.058, p &amp;lt; 0.001, R2 = 0.116]. By contrast, number of stressful experiences was not associated with cognitive outcomes. Follow up analyses indicated that CAPS severity scores were significantly associated with the memory index and the attention index of the MoCA. Conclusions In a sample of older veterans, PTSD symptom severity was associated with worse performance on the MoCA. Moreover, further analyses indicated that results within the memory and attention domains are driving these results. As such, treating PTSD symptoms may be helpful in maintaining cognitive function as adults age.

Associations between maternal lifetime stressors and negative events in pregnancy and breast milk-derived extracellular vesicle microRNAs in the programming of intergenerational stress mechanisms (PRISM) pregnancy cohort

ABSTRACT Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20–80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |B regression|>0.2. Enriched KEGG pathways for microRNAs associated with stress scores included fatty acid metabolism and the Hippo signaling pathway. Maternal lifetime stress and NLEs during pregnancy were both associated with detection and expression level of breast milk EV-microRNAs, although associations with microRNA profiles differed between stress measures. Further research is needed to identify biological pathways impacted by associated microRNAs and investigate relationships with child health outcomes. Abbreviations: EV: extracellular vesicle; PRISM: PRogramming of Intergenerational Stress Mechanisms pregnancy cohort; LSCR: Life Stressor Checklist-Revised survey; NLE: negative life event; CRISYS-R: Crisis in Family Systems-Revised survey; KEGG: Kyoto Encyclopaedia of Genes and Genomes; NYC: New York City; SD: standard deviation; IQR: interquartile range; Cq: relative cycle threshold values; PCA: principal component analysis

Maternal stress in relation to sex-specific expression of placental genes involved in nutrient transport, oxygen tension, immune response, and the glucocorticoid barrier

IntroductionMurine models provide evidence that maternal stress during pregnancy can influence placenta morphology and function, including altered expression of genes involved in the maintenance and progression of pregnancy and fetal development. Corresponding research evaluating the impact of maternal stress on placental gene expression in humans is limited. We examined maternal stress in relation to placental expression of 17 candidate genes in a community-based sample. MethodsParticipants included 60 mother-newborn pairs enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based at the Mount Sinai Hospital in New York City. Placentas were collected immediately following delivery and gene expression was measured using a qPCR-based platform. Maternal experiences of traumatic and non-traumatic stress were measured using the Life Stressor Checklist-Revised (LSC-R) administered during a mid-pregnancy interview. We used multivariable linear regression to examine associations between LSC-R scores and expression of each gene in separate models in the sample overall and stratified by fetal sex. ResultsHigher maternal stress was associated with significantly increased placental expression of the nutrient sensor gene OGT, the glucose transporter gene GLUT1, and the hypoxia sensor gene HIF3A. In models stratified by fetal sex, significant associations remained only among males. DiscussionThis study represents one of the most comprehensive examinations of maternal lifetime traumatic and non-traumatic stress in relation to placental gene expression in human tissue. Our findings support that maternal stress may alter sex-specific placental expression of genes involved in critical developmental processes.

Longitudinal study of PTSD and depression in a war-exposed sample – comorbidity increases distress and suicide risk

Abstract Background Major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are the most common mental disorders following traumatic experiences. The aim of this study was to investigate the extent to which PTSD and depression co-occurred in Serbian general population at baseline and 1 year after the follow-up, as well as how this co-occurrence was associated with sociodemographic factors, personal distress, suicidality and quality of life. Subjects and methods The sample consisted of 159 subjects, who fulfilled the IES criteria for PTSD, and were taken from a larger sample of 640 participants, which was chosen by a random walk technique in five regions of the country affected by major trauma. The assessment was carried out by the following instruments: Mini International Neuropsychiatric Interview 5 (MINI 5), Life Stressor Checklist-Revised (BSC-R), Brief Symptom Inventory (BSI), Impact of Event Scale-Revised (IES-R) and Manchester Short Assessment of Quality of Life Scale (MANSA). The follow-up study was carried out 1 year after the baseline. Results In the initial phase, PTSD was found in 100 out of 159 participants (62.9%), while 81 (51%) fulfilled the diagnostic criteria for MDD. Comorbidity of PTSD and depression was identified in 65 (40.9%) subjects of the sample. After 1 year, PTSD was found in 56 (35.2%) and MDD in 73 (45.9%) participants. Comorbidity of PTSD and depression in the follow-up phase was identified in 41 (25.8%) subjects of the sample. The subjects with comorbidity had significantly higher level of post-traumatic stress symptoms, general psychological distress as well as suicide risk and lower level of quality of life than participants with either condition alone. Conclusion PTSD–depression comorbidity is a common post-traumatic condition. Complex psychopathology, severity of symptoms and their consequences, both at individual and community levels, require attention to be paid to early diagnostics and treatment of affected persons.