Multiple Infections, Nutrient Deficiencies, and Inflammation as Determinants of Anemia and Iron Status during Pregnancy: The MINDI Cohort.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Characterizing Life Stress Exposure Among Sexual Minority Adolescents: Temporality, Content, And Mediating Role in Mental Health Disparities.

Though sexual minority adolescents face a wide array of deleterious stressors, few studies have examined the role of specific types of stress exposure (i.e., chronic vs. episodic, interpersonal vs. non-interpersonal) on mental health disparities. This study utilizes a contextual threat-based assessment to (a) compare levels of stress exposure types between sexual minority and non-sexual minority adolescents, and (b) examine stress type as a mediator between sexual orientation and two outcomes: depressive symptoms and emotion dysregulation. Data comes from a longitudinal sample (14-17 years-old, N = 241; 17.6% sexual minority; 54% assigned female at birth; 73.9% White), with two time-points (T1 and T2) utilized. Sexual minority adolescents reported higher chronic interpersonal stress, but no differences in non-interpersonal chronic or episodic stress, relative to non-sexual minority adolescents. Chronic interpersonal stress exposure mediated the link between membership in an oppressed group (i.e., sexual minority teens) and the primary outcomes (emotion dysregulation and depressive symptoms) at both T1 and T2. Findings demonstrate the utility of contextual threat-based assessments within sexual minority research.

Everyday emotion, naturalistic life stress, and the prospective prediction of adolescent depression.

BACKGROUND AND OBJECTIVES: Increasing research underscores low positive emotion (PE) as a vital component of depression risk in adolescence. Theory also suggests that PE contributes to adaptive coping. However, it is unclear whether naturalistic experiences of emotions contribute to long-term depression risk, or whether daily PE levels equip adolescents to cope with later naturalistic stressors, reducing risk for depression. The current study examines whether PE (and negative emotion [NE]) assessed via ecological momentary assessment (EMA) (a) predict prospective increases in depression, and (b) moderate the association between later life stressors and depression. DESIGN: Longitudinal study of community-recruited adolescents, with EMA at baseline. METHOD: Adolescents (n = 232) completed contextual threat life stress interviews, interview and self-report measures of depression at baseline and 1.5 year follow-up. At baseline, they completed a seven-day EMA of emotion. RESULTS: Preregistered analyses showed that daily NE, but not PE, predicted increased depression over time and moderated the association between interpersonal episodic stress and self-reported depression. CONCLUSIONS: Results did not support daily PE as a buffer against depressogenic effects of life stress, but point to daily NE as a marker of depression risk.

Patterns of life stress and the development of ruminative brooding in adolescence: A person-centered approach.

Research links life stressors, including acute, chronic, and early life stress, to the development of ruminative brooding. However, singular forms of life stress rarely occur in isolation, as adolescents typically encounter stressors that vary on important dimensions (e.g., types, timings, quantities) across development. The current study employs latent profile analysis (LPA) to identify natural clusters of life stress that, over time, may be differently associated with ruminative brooding. Evaluations of episodic, chronic, and early life stress were conducted with community-recruited mid-adolescents (N = 241, Mage = 15.90 years, 53% female) and their parents using the UCLA Life Stress Interview and lifetime adversity portions of the Youth Life Stress Interview. Analyses identified four distinct patterns: low stress, high peer stress, moderate home / family stress, and multifaceted / high school stress. Adolescents in the high peer stress and moderate home / family stress profiles were at highest risk for developing a brooding style over time. Despite high overall levels of stress, teens in the multifaceted / high school stress profile were at not at elevated risk for developing a brooding style. Findings demonstrate the utility of person-centered approaches to identify patterns of stress exposure that heighten risk for brooding over time.

Negative emotion differentiation in trauma-exposed community members: Associations with posttraumatic stress disorder symptoms in daily life.

The ability to make fine-grained distinctions between discrete negative emotions-termed negative emotion differentiation (NED)-is important for emotion regulation and psychological well-being. Posttraumatic stress disorder (PTSD) is associated with elevated trauma-related negative emotions (e.g., fear, anger, guilt, shame) and self-reported difficulty identifying feelings, suggesting that low NED may be a feature of PTSD. PTSD is also characterized by overreliance on avoidance as an emotion regulation strategy-a characteristic that could be influenced by low NED. Here, we examined whether NED is reduced in PTSD and the role NED plays in the association between trauma-related avoidance and other PTSD symptoms (traumatic reexperiencing, negative alterations in cognition and mood, alterations in arousal and reactivity). Hypotheses were tested using 3 days of ecological momentary assessment (up to 17 prompts per day) in 80 trauma-exposed participants (39 with PTSD, 41 without PTSD; total completed surveys = 2,158). NED was reduced and self-reported difficulty identifying feelings was elevated in those with PTSD, and both predicted PTSD severity (Clinician-Administered PTSD Scale-5 score) and momentary PTSD symptoms. Furthermore, low NED, but not difficulty identifying feelings, predicted a stronger association between momentary trauma-related avoidance and PTSD symptoms. Results suggest that NED is involved in the emotional processing of trauma by decreasing the negative impact of avoidance behavior on other PTSD symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The vicious cycle of psychopathology and stressful life events: A meta-analytic review testing the stress generation model.

Stress generation theory initially posited that depression elevates risk for some stressful events (i.e., dependent events) but not others (i.e., independent events). This preregistered meta-analytic review examined whether stress generation occurs transdiagnostically by examining 95 longitudinal studies with 38,228 participants (537 total effect sizes) from over 30 years of research. Our multilevel meta-analyses found evidence of stress generation across a broad range of psychopathology, as evidenced by significantly larger prospective effects for dependent (overall psychopathology: r = .23) than independent (overall psychopathology: r = .10) stress. We also identified unique patterns of effects across specific types of psychopathology. For example, effects were larger for depression than anxiety. Furthermore, effects were sometimes larger in studies with younger participants, shorter time lags between assessments, checklist measures of stress, and for interpersonal stressors. Finally, a multilevel meta-analytic structural equation model suggested that dependent stress exacerbates psychopathology symptoms over time (ß = .04), possibly contributing to chronicity. Interventions targeting the prevention of stress generation may mitigate chronic psychopathology. Conclusions of this study are limited by the predominance of depression effect sizes in the literature and our review of only English language articles. On the other hand, the findings are strengthened by rigorous inclusion criteria, lack of publication bias, and absence of moderating effects by publication year. The latter underscores the replicability of the stress generation effect over the last 30 years. Taken together, the review provides robust evidence that stress generation is a cross-diagnostic phenomenon that contributes to a vicious cycle of increasing stress and psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk and protective factors for stress generation: A meta-analytic review.

The stress generation hypothesis suggests that some individuals contribute more than others to the occurrence of dependent (self-generated), but not independent (fateful), stressful life events. This phenomenon is commonly studied in relation to psychiatric disorders, but effects are also driven by underlying psychological processes that extend beyond the boundaries of DSM-defined entities. This meta-analytic review of modifiable risk and protective factors for stress generation synthesizes findings from 70 studies with 39,693 participants (483 total effect sizes) from over 30 years of research. Findings revealed a range of risk factors that prospectively predict dependent stress with small-to-moderate meta-analytic effects (rs = 0.10-0.26). Negligible to small effects were found for independent stress (rs = 0.03-0.12), and, in a critical test for stress generation, most effects were significantly stronger for dependent compared to independent stress (ßs = 0.04-0.15). Moderation analyses suggest effects of maladaptive interpersonal emotion regulation behaviors and repetitive negative thinking are stronger for interpersonal (versus non-interpersonal) stress; effects of repetitive negative thinking and excessive standards for self may be inflated by overreliance on self-report measures that fail to isolate psychological distress from objective experience. Findings have key implications for advancing stress generation theory and informing targets for intervention.

Multiple Indicators of Undernutrition, Infection, and Inflammation in Lactating Women Are Associated with Maternal Iron Status and Infant Anthropometry in Panama: The MINDI Cohort.

Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (ß = −0.22), WAZ (ß = −0.17), and LAZ (ß = −0.17). Higher LAZ was also associated with maternal serum vitamin D (ß = 0.23), whereas maternal iron supplementation lowered LAZ (ß = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

Measurement invariance of the Interpersonal Needs Questionnaire (INQ-15) across sexual orientation, gender identity, and race/ethnicity in a sample of sexual minority young adults.

Sexual minority (e.g., gay, lesbian, bisexual) people are at increased risk for suicidal thoughts and behaviors compared to their heterosexual peers. The interpersonal theory of suicide proposes that perceived burdensomeness and thwarted belongingness are central to the desire to die, and both are associated with suicidal ideation in sexual minority samples. The Interpersonal Needs Questionnaire (INQ) was developed to measure these risk factors and has become the most commonly used measure. However, it is unknown whether the INQ demonstrates similar measurement properties across subgroups of sexual minority people. Therefore, the goal of this study was to examine whether the 15-item version of the INQ exhibited measurement invariance (MI) across sexual orientation (gay/lesbian vs. bi +), gender identity (cisgender men vs. cisgender women vs. transgender/gender diverse individuals), and race/ethnicity (non-Latinx White individuals vs. people of color) in a sample of 792 sexual minority young adults (ages 18-29). A series of multigroup measurement invariance models indicated that the INQ-15 met strict invariance (i.e., equal factor loadings, item intercepts, and residual variances) across all three dimensions of identity. This indicates that it can be used and compared across diverse samples of sexual minority young adults. Results also indicated that perceived burdensomeness was greater for transgender/gender diverse individuals than for cisgender men and women, and that perceived burdensomeness and thwarted belongingness were greater for people of color than for non-Latinx White individuals. In contrast, gay/lesbian and bi + individuals did not differ. Additional research is needed to understand the factors that account for these group differences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

INTERGROWTH-21 Identifies High Prevalence of Low Symphysis-Fundal Height in Indigenous Pregnant Women Experiencing Multiple Infections, Nutrient Deficiencies, and Inflammation: The Maternal Infections, Nutrient Deficiencies, and Inflammation (MINDI) Cohort.

BACKGROUND: In the absence of ultrasound, symphysis-fundal height (SFH) can assess maternal-fetal well-being as it is associated with gestational age, fetal weight, and amniotic fluid volume. However, other modifiers of SFH, including maternal infections, nutrient deficiencies, and inflammation (MINDI), have not been widely explored. OBJECTIVES: Our objectives were 2-fold: 1) to assess prevalence of low SFH in indigenous Panamanian women using both Pan-American Health Organization (PAHO) and INTERGROWTH-21 standards and 2) to explore associations of SFH with maternal health indicators: infections (oral, skin, urogenital, nematode infections), nutrient deficiencies [protein and iron indicators (ferritin, serum iron, serum transferrin receptor, hepcidin), folate, and vitamins A, D, and B-12], and inflammation [leukocytes, C-reactive protein (CRP), cytokines]. METHODS: For this cross-sectional study, low-SFH-for-gestational-age was assessed using PAHO and INTERGROWTH <10th centile in 174 women at ≥16 weeks of gestation. Bootstrapping selected MINDI variables for inclusion in multivariable fractional polynomial (MFP) logistic regressions for low SFH. Associations of MINDI variables with hepcidin were also investigated. RESULTS: Prevalence of low SFH was 8% using PAHO, but using INTERGROWTH, 50.6% had SFH <10th centile, including 37.9% <3rd centile. Both PAHO-SFH <10th centile and INTERGROWTH-SFH <3rd centile were associated with higher hepcidin (OR = 1.12, P = 0.008, and OR = 3.04, P = 0.001, respectively) and with lower TNF-α (OR = 0.73, P = 0.012, and OR = 0.93, P = 0.015, respectively). Wood-smoke exposure increased the odds of PAHO-SFH <10th centile (OR = 1.19, P = 0.009), whereas higher BMI decreased the odds of INTERGROWTH-SFH <3rd centile (OR = 0.87, P = 0.012). Lower pulse pressure (OR = 0.90, P = 0.009) and lower inflammatory responses [lower lymphocytes (OR = 0.21, P = 0.026), IL-17 (OR = 0.89, P = 0.011)] distinguished SFH <3rd centile from SFH ≥3rd to <10th centiles using INTERGROWTH-21 standards. The MFP regression for hepcidin controlling for SFH (adjusted R 2 = 0.40, P = 0.001) revealed associations with indicators of inflammation (CRP, P < 0.0001; IL-17, P = 0.012), acidic urinary pH (P = 0.008), and higher intake of supplements (P = 0.035). CONCLUSIONS: Associations of low SFH with MINDI variables, including hepcidin, highlight its potential for early detection of multicausal in utero growth faltering.

Distinguishing Transdiagnostic versus Disorder-Specific Pathways between Ruminative Brooding and Internalizing Psychopathology in Adolescents: A Latent Variable Modeling Approach.

Rumination is correlated with diverse types of internalizing problems, but the extent to which it relates to a higher-order internalizing spectrum versus disorder-specific pathology is unclear. Using a quantitative model of the internalizing dimension, we compared the strength of transdiagnostic versus diagnosis-specific pathways from brooding-the most depressogenic component of rumination-to major depressive disorder (MDD) in adolescents. Community-recruited mid-adolescents (N = 241, Mage = 15.90 years, 53% female) completed semi-structured interviews of anxiety and depressive conditions and a self-report brooding measure. Confirmatory factor analysis revealed good fit for a one-factor model of internalizing conditions. Results revealed a large, significant factor correlation between brooding and the internalizing factor (r = 0.55), with some evidence for a more modest specific link between brooding and the unique component of the MDD diagnosis (r = 0.17; approximately one-third as large as the transdiagnostic pathway). These cross-sectional associations were generally consistent across two assessment waves separated by 19 months. We concluded that brooding is better conceptualized as a common characteristic of all internalizing problems in adolescence, rather than a specific feature of MDD. Preregistered hypotheses, data analysis code, and correlation matrices for this study are posted at https://osf.io/dax7u/ .

Stress sensitization to depression following childhood adversity: Moderation by HPA axis and serotonergic multilocus profile scores.

Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic-pituitary-adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a "gene-by-environment-by-environment" interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

Negative Emotion Differentiation through a Developmental Lens: Associations with Parental Factors and Age in Adolescence.

Negative emotion differentiation (NED) is the ability to precisely discern negatively-valenced emotional states. Low NED has been linked to numerous negative outcomes. However, little is known about the conditions under which individual differences in NED emerge, particularly during adolescence, a potentially important developmental stage. We examined associations between NED (assessed using intraclass correlations between negative emotion [NE] ratings collected via intensive longitudinal methods), parental variables, and age. Adolescents (N=233, M age=15.90, 53% female) and their parents completed interview measures of depression and self-report questionnaires; adolescents then completed a seven-day ecological momentary assessment. Lower NED was associated with greater parental depression, greater authoritarian parenting style, and lower parental attachment security. Age was negatively and linearly associated with NED. Results held controlling for mean NE and adolescent depression, although authoritarian parenting was non-significant controlling for other developmental variables. Findings suggest healthy parent-child relationships may relate to adolescents' ability to perceive NEs with nuance.

Nodal is required to maintain the uterine environment in an anti-inflammatory state during pregnancy†.

Preterm birth remains the major cause of perinatal mortality and morbidity worldwide, affecting up to 12% of pregnancies and accounting for ~75% of neonatal deaths. However, the mechanisms and causes that underlie it are still largely unknown. One of the major causes of preterm birth is infection or inflammation within the maternal-fetal interface. Our lab has previously shown that a uterine specific deletion of Nodal results in mutant females delivering 2 days prior to term demonstrating an important role for this factor in the maintenance of pregnancy. Here, we have addressed the function of Nodal in the uterus during pregnancy. We demonstrate that Nodal heterozygous mice have an increase in basal levels of pro-inflammatory cytokines IL-1ß, IL-6, IL-12p, TNF-α, and IFN-γ as well as an increase in the number of macrophages in response to the inflammatory agent, lipopolysaccharide (LPS). Using bone marrow-derived macrophages, we demonstrated that pretreatment with recombinant Nodal reduces pro-inflammatory gene expression when these cells are challenged with LPS. Our results demonstrate that Nodal is required to maintain the uterine environment in an anti-inflammatory state by preventing proinflammatory cytokine expression.

The perils of murky emotions: Emotion differentiation moderates the prospective relationship between naturalistic stress exposure and adolescent depression.

Negative emotion differentiation (NED) refers to the ability to identify and label discrete negative emotions. Low NED has been previously linked to depression and other indices of low psychological well-being. However, this construct has rarely been explored during adolescence, a time of escalating depression risk, or examined in the context of naturalistic stressors. Further, the association between NED and depression has never been tested longitudinally. We propose a diathesis-stress model wherein low NED amplifies the association between stressful life events (SLEs) and depression. A sample of 233 community-recruited midadolescents (Mage 15.90 years, 54% female) completed diagnostic interviews and reported on mood and daily stressors 4 times per day for 7 days. SLEs were assessed using a semistructured interview with diagnosis-blind team coding based on the contextual threat method. Follow-up interviews were conducted 1.5 years after baseline. Low NED was correlated with depression but did not predict prospective changes in depression as a main effect. Confirming predictions and supporting a diathesis-stress model, low NED predicted (a) within-subjects associations between daily hassles and momentary depressed mood, (b) between-subjects associations between SLE severity and depression, and (c) prospective associations between SLE severity and increases in depression at follow-up. Results were specific to negative (vs. positive) emotion differentiation. Results suggest that low NED is primarily depressogenic in the context of high stress exposure. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Interpersonal childhood adversity and stress generation in adolescence: Moderation by HPA axis multilocus genetic variation.

Research suggests that childhood adversity (CA) is associated with a wide range of repercussions, including an increased likelihood of interpersonal stress generation. This may be particularly true following interpersonal childhood adversity (ICA) and for youth with high hypothalamic-pituitary-adrenal (HPA) axis-related genetic risk. In the current study, we applied a multilocus genetic profile score (MGPS) approach to measuring HPA axis-related genetic variation and examined its interaction with ICA to predict interpersonal stress generation in a sample of adolescents aged 14-17 (N = 241, Caucasian subsample n = 192). MGPSs were computed using 10 single nucleotide polymorphisms from HPA axis-related genes (CRHR1, NRC31, NRC32, and FKBP5). ICA significantly predicted greater adolescent interpersonal dependent stress. Additionally, MGPS predicted a stronger association between ICA and interpersonal dependent (but not independent or noninterpersonal dependent) stress. No gene-environment interaction (G×E) effects were found for noninterpersonal CA and MGPS in predicting adolescent interpersonal dependent stress. Effects remained after controlling for current depressive symptoms and following stratification by race. Findings extend existing G×E research on stress generation to HPA axis-related genetic variation and demonstrate effects specific to the interpersonal domain.

The developmental origins of ruminative response style: An integrative review.

Rumination has been conceptualized as a stable, trait-level response style involving repetitive and passive focus on the symptoms of distress and the possible causes and consequences of those symptoms. This theoretical review examines developmental risk factors of ruminative response style, incorporating a developmental psychopathology perspective. A model integrating these developmental factors within a conceptual framework is proposed, wherein risk factors for distress (i.e., temperamental negative affectivity, stressful environments, parenting, and genetic vulnerability) lead to engagement in rumination. We propose that when rumination is well-practiced, it will consolidate into a trait-like response style, especially among adolescents who experience cognitive control deficits. Reciprocal relationships and moderators that may contribute to the formation of a ruminative response style are also included. To understand how these factors converge and influence the formation of ruminative response styles, we review patterns of stability and change in physical and cognitive development to demonstrate that individual differences in rumination may emerge and consolidate into enduring, trait-level response styles during early adolescence.

Serotonergic multilocus genetic variation moderates the association between major interpersonal stress and adolescent depressive symptoms: Replication and candidate environment specification.

Serotonin-linked genetic risk and stressful life event (SLE) interaction research has been criticized for using single genetic variants with inconsistent replicability. A recent study showed that a multilocus genetic profile score (MGPS) capturing additive risk from five serotonin-linked polymorphisms moderated the association between major interpersonal SLEs and depression, but no subsequent replication attempts have been reported. Moreover, major interpersonal SLEs have been suggested as "candidate environments" for this MGPS, but it has never been demonstrated that gene-environment interactions (G × Es) for major interpersonal SLEs are significantly stronger than for other contexts. Adolescents (N = 241) completed contextual-threat life stress interviews and clinical interviews assessing depressive symptoms, and provided DNA. MGPS intensified the major interpersonal stress-depression association; the interaction accounted for 4% of depressive symptom variance. Genetic moderation was statistically unique to major interpersonal stress versus other environments. Extending previous findings, results support an MGPS approach and underscore the cruciality of the G × E candidate environment.