Introduction
Exposure to traumatic events and stressful life experiences are associated with a wide range of adverse mental and physical health outcomes. Studies have found post-traumatic stress disorder (PTSD), depression, and anxiety sensitivity occurrence to be common in addition to inflammatory diseases like asthma, especially in women. Moreover, overlapping neurobiological mechanisms have been linked to both PTSD and asthma.
Methods
In the current study, n = 508 women reported on presence of lifetime asthma diagnosis and symptoms of trauma-related psychopathology including PTSD and depression. A separate group of female participants (n = 64) reported on asthma, PTSD, depression and anxiety sensitivity, and underwent functional MRI scans during a fearful faces task, and their anterior insula responses were analyzed.
Results
Overall, PTSD and depression severity were significantly higher in those with asthma versus those without asthma. There was a positive association between anterior insula response to social threat cues and depression symptoms only among individuals without a lifetime presence of asthma.
Discussion
These findings provide continued evidence on the interactions between stress, neural mechanisms involved in interoception and salience detection, and trauma-related psychopathology.
Background
Mood disorders such as major depressive and bipolar disorders, along with posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and other psychotic disorders, constitute serious mental illnesses (SMI) and often lead to inpatient psychiatric care for adults. Risk factors associated with increased hospitalization rate in SMI (H-SMI) are largely unknown but likely involve a combination of genetic, environmental, and socio-behavioral factors. We performed a genome-wide association study in an African American cohort to identify possible genes associated with hospitalization due to SMI (H-SMI).
Methods
Patients hospitalized for psychiatric disorders (H-SMI; n=690) were compared with demographically matched controls (n=4467). Quality control and imputation of genome-wide data were performed following the Psychiatric Genetic Consortium (PGC)-PTSD guidelines. Imputation of the Human Leukocyte Antigen (HLA) locus was performed using the HIBAG package.
Results
Genome-wide association analysis revealed a genome-wide significant association at 6p22.1 locus in the ubiquitin D (UBD/FAT10) gene (rs362514, p=9.43x10-9) and around the HLA locus. Heritability of H-SMI (14.6%) was comparable to other psychiatric disorders (4% to 45%). We observed a nominally significant association with 2 HLA alleles: HLA-A*23:01 (OR=1.04, p=2.3x10-3) and HLA-C*06:02 (OR=1.04, p=1.5x10-3). Two other genes (VSP13D and TSPAN9), possibly associated with immune response, were found to be associated with H-SMI using gene-based analyses.
Conclusion
We observed a strong association between H-SMI and a locus that has been consistently and strongly associated with SCZ in multiple studies (6p21.32-p22.1), possibly indicating an involvement of the immune system and the immune response in the development of severe transdiagnostic SMI.
Background: Higher subjective social status (SSS) or a person’s perception of their social standing is related to better health outcomes, but few studies examined SSS in relation to obesity. Emotional eating and food addiction have been linked to obesity. Some studies indicated that manipulating SSS may lead to altered food intake, but the relationship between SSS and dysregulated eating, such as emotional eating and food addiction (FA), has not been examined. The goal of this study was to examine the associations between SSS in the community and the larger society, dysregulated eating (emotional eating and FA), and body mass index (BMI) in a majority racial minority sample. Methods: The participants (N = 89; 93% Black, 86% women, and 56% with obesity; 72% income lower than USD 2000), recruited from a publicly funded hospital in Atlanta, GA, completed the MacArthur Scale, Dutch Eating Behaviors Questionnaire, Yale Food Addiction Scale, Beck Depression Inventory, PTSD Symptom Checklist, and demographics questionnaire. Results: Twentytwo percent of the sample met the criteria for FA; those with FA had significantly higher BMI than those without (p = 0.018). In the hierarchical linear regression, the SSS community (but not in society) predicted higher severity of emotional eating (β = 0.26, p = 0.029) and FA (β = 0.30, p = 0.029), and higher BMI (β = 0.28, p = 0.046), independent from depression and PTSD symptoms. Conclusions: The findings indicate that, among Black individuals with predominantly low income in the U.S., perceived role in their community is associated with eating patterns and body mass. Given the small sample size, the results should be interpreted with caution.
C-reactive protein (CRP), a marker of systemic inflammation, has been associated with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Emotion dysregulation is a transdiagnostic risk factor for many psychological disorders associated with chronic inflammatory state. The objective of this study was to determine whether inflammation is associated with emotion dysregulation in women with type 2 diabetes mellitus (T2DM). We examined associations between trauma exposure, MDD, PTSD, emotion dysregulation, and CRP among 40 African-American women with T2DM recruited from an urban hospital. Emotion dysregulation was measured using the Difficulties in Emotion Regulation Scale. PTSD and MDD were measured with structured clinical interviews. Child abuse and lifetime trauma load were also assessed. Analyses showed that both emotion dysregulation and current MDD were significantly associated with higher levels of CRP (p < 0.01). Current PTSD was not significantly related to CRP. In a regression model, emotion dysregulation was significantly associated with higher CRP (p < 0.001) independent of body mass index, trauma exposure, and MDD diagnosis. These findings suggest that emotion dysregulation may be an important risk factor for chronic inflammation beyond already known risk factors among women with T2DM, though a causal relationship cannot be determined from this study.
Objective:
C-reactive protein (CRP), a marker of systemic inflammation, has been associated with psychiatric disorders including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Some research suggests that exposure to trauma can trigger increased activity in the inflammatory system. Dissociation is associated with chronic trauma exposure and may be an important factor in understanding the risk for psychiatric outcomes associated with inflammation. The main objective of the current study was to understand how CRP was related to trauma, dissociation, PTSD and MDD in a sample of 55 traumatized African American women with type 2 diabetes mellitus recruited from an urban hospital.
Method:
High sensitivity CRP (hsCRP) was assayed through blood samples; psychiatric disorders were assessed with structured clinical interviews, dissociation was assessed with the Multiscale Dissociation Inventory, and exposure to trauma in childhood and adulthood was assessed with the Childhood Trauma Questionnaire and the Traumatic Events Inventory, respectively.
Results:
Correlational results showed a significant association between higher concentrations of hsCRP and child abuse (p<.05), overall dissociation severity (p<.001), and PTSD symptoms (p<.01). ANOVA results showed significantly higher levels of hsCRP in those with current MDD, current PTSD, and remitted PTSD. A hierarchical linear regression model demonstrated a significant association between dissociation symptoms and greater hsCRP levels independent of childhood abuse, PTSD, and MDD (R2Δ=0.11, p=.001) and independent of emotion dysregulation (p<.05)
Conclusion:
These findings suggest that dissociation symptoms among those with a history of trauma may be particularly associated with higher levels of inflammation.
Background: Immune dysregulation has been widely observed in those with posttraumatic stress disorder (PTSD). An individual's immune response is shaped, in part, by the highly polymorphic Human Leukocyte Antigen (HLA) locus that is associated with major psychiatric disorders such as schizophrenia, major depression and bipolar disorder. The aim of the current study was to investigate the association between common HLA alleles and PTSD. Methods: Genome-wide association data was used to predict alleles of 7 classical polymorphic HLA genes (A, B, C, DRB1, DQA1, DQB1, DPB1) in 403 lifetime PTSD cases and 369 trauma exposed controls of African ancestry. Association of HLA allelic variations with lifetime PTSD was analyzed using logistic regression, controlling for ancestry, sex and multiple comparisons. The effect of HLA alleles on gene expression was assessed by weighted correlation network analysis (WGCNA), using 353 subjects with available expression data. Enrichment analysis was performed using anRichment to identify associated pathways of each module. Results: HLA-B*58:01 (p = 0.035), HLA-C*07:01 (p = 0.035), HLA-DQA1*01:01 (p = 0.003), HLA-DQB1*05:01 (p = 0.009) and HLA-DPB1*17:01 (p = 0.017) were more common in PTSD cases, while HLA-A*02:01 (p = 0.026), HLA-DQA1*05:05 (p = 0.011) and HLA-DRB1*11:01 (p < 0.001) were more frequent in controls. WGCNA was used to explore expression patterns of the PTSD related alleles. Gene expression modules of PTSD-related HLA alleles were enriched in various pathways, including pathways related to immune and neural activity. Conclusions: To the best of our knowledge, this is the first study to report an association of HLA alleles with PTSD. Altogether, our results support the link between the immune system, brain and PTSD.
Food addiction (FA) describes a group of disordered eating behaviors. Childhood trauma has been associated with adult FA and trauma has known effects on the endocrine system, but it is unclear whether FA is associated with insulin resistance. We hypothesized that severity of childhood trauma will be associated with FA and higher insulin resistance (HOMA-IR) in a sample of obese women with type 2 diabetes mellitus (T2DM), and that FA will mediate the association between childhood trauma and HOMA-IR. Women with a diagnosis of T2DM (N = 73; MBMI = 35.86, SDBMI = 7.72; Mage = 50.59, SDage = 9.72) were recruited from a diabetes clinic at a county hospital. Participants completed the Childhood Trauma Questionnaire and the Yale Food Addiction Scale. Fasting blood samples were obtained from 64 participants to assess plasma hemoglobin A1c (HbA1c), insulin and glucose (used to calculate HOMA-IR); Oral Glucose Tolerance Test (OGTT) was performed to measure change in glucose and insulin secretion. 48% of the sample met diagnostic criteria for FA. Women with FA reported significantly higher HOMA-IR (F = 25.692, p < 0.001, df = 1,62), HbA1c (F = 4.358, p = 0.041, df = 1,62), and OGGT glucose (F = 5.539, p = 0.022, df = 1,62) as well as severity of childhood trauma (F = 10.453, p = 0.002, df = 1,71). In a hierarchical linear regression controlling for BMI, income level, and T2DM treatment, the severity of childhood trauma did not contribute to the prediction of HOMA-IR (β = −0.011, p = 0.942) whereas FA did (β = 0.422, p = 0.007). In a bootstrapped mediation analysis, the association between childhood trauma and HOMA-IR was mediated by FA severity (b = 0.596, p = 0.020). Understanding the psychological factors that contribute to HOMA-IR in an underserved population of African American women may lead to more effective diabetes management and prevention strategies.
Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n = 62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n = 37) and PTSD+ (n = 25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p < 0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's ≤ 0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p < 0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.
Positive and negative affect are both associated with health outcomes. Using validated measures, we examined associations between affect, self-reported measures of health, and objective measures of systemic inflammation in a cross-sectional sample of outpatient subjects recruited from an urban county hospital. Participants (n = 1055) recruited from the Grady Trauma Project in Atlanta, GA underwent standardized interviews including self-report measures of psychiatric symptoms and physical health. A subset (n = 246) consented to an assay of serum C-reactive protein (CRP). Regression models including positive affect as the predictor variable with covariates of age, gender, income, trauma load, depression and PTSD symptoms, were significantly associated with physical health domain scales of the Short Form-36 Health Survey (SF-36) of general health (R2 = 0.212; p < 0.001) and physical functioning (R2 = 0.154; p = 0.013). No association was observed using negative affect as the predictor variable. While greater serum CRP concentrations were associated with less positive affect (r = −0.137; p = 0.038), this relationship did not remain significant (p = 0.250) when controlling for demographic variables, body mass index, trauma load, and psychiatric symptoms. Future studies using larger samples or samples with more variance for CRP and positive and negative affect may be helpful in investigating the relationship between CRP and positive and negative affect. Our results support the hypothesis that positive affect contributes beneficially to physical health. Development of strategies to enhance positive affect in at-risk populations may be a meaningful way to improve their health.
The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in “energetic stress” that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant.