Characterization of the inflammatory response to COVID-19 illness in pregnancy.

OBJECTIVE: Pregnant patients face greater morbidity and mortality from COVID-19 related illness than their non-pregnant peers. Previous research in non-pregnant patients established that poor clinical outcomes in SARS-CoV-2 positive patients admitted to the ICU were correlated with a significant increase in the proinflammatory markers interleukin (IL)-1ß, IL-6, IL-8, and IL-10. Importantly, high levels of these inflammatory markers have also been associated with adverse pregnancy outcomes, including spontaneous preterm birth, preeclampsia, and severe respiratory disease. STUDY DESIGN: This was a retrospective cohort study that compared the serum inflammatory cytokine profiles of pregnant patients with acute/post-acute SARS-CoV-2 infection to those with previous exposure. All subjects in both cohorts tested positive for SARS-CoV-2 antibodies; however, those in the acute/post-acute infection cohort had a documented positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) result within 30 days of serum sample collection. Serum samples were obtained during prenatal venipuncture from 13 to 39 weeks' gestation and the cohorts were matched by gestational age. The inflammatory cytokines interferon (IFN)-γ, IL-10, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor (TNF)-α were assayed from maternal serum using a standard ELISA assay and median cytokine concentrations were compared using the Mann-Whitney test. RESULTS AND DISCUSSION: We enrolled 50 non-Hispanic Black patients with confirmed COVID-19 infection who received prenatal care at Grady Memorial Hospital in Atlanta, Georgia. Those with acute/post-acute infection (n = 22) had significantly higher concentrations of SARS-CoV-2 antibody, IL-10, IL-1ß, and IL-8, while patients with previous exposure (n = 28) had significantly higher concentrations of IL-4. There were no significant inter-group differences in medical comorbidities. Pregnant patients with acute/post-acute SARS-CoV-2 infection had significantly higher serum concentrations of pro-inflammatory cytokines as compared to those with previous exposure, suggesting that, like in the non-pregnant population, SARS-CoV-2 infection alters the levels of circulating proinflammatory markers during pregnancy. The increased levels of cytokines may contribute to the adverse obstetric outcomes observed with COVID-19 illness.

WHEN REPRODUCTION IS NO LONGER AUTONOMOUS: FEELING RESPECTED BY MATERNITY CARE PROVIDERS MODERATES THE ASSOCIATION BETWEEN AUTONOMY IN DECISION MAKING AND BIRTH-RELATED PTSD SYMPTOMS IN A COMMUNITY SAMPLE OF POSTPARTUM BLACK WOMEN.

Black individuals are at particularly high risk for birth-related posttraumatic stress disorder (PTSD) symptoms, in part due to a lack of opportunity to lead maternity care decisions. Maternal care providers need evidence-based ways to reduce pregnant persons' risk for birth-related PTSD symptoms despite reduced autonomy in decision making resulting from heightened restrictions on reproductive rights. We investigated whether a potential relation between autonomy in decision making and birth-related PTSD symptoms would be moderated by being mistreated or feeling respected by maternity care providers in a community sample of Black women (N = 52; Mage = 28.2 years, SDage = 5.7 years) seeking maternity care at a public hospital in the southeastern United States. At six weeks postpartum, participants completed measures assessing autonomy in decision making, current birth-related PTSD symptoms, number of mistreatment events, and feelings of respect from providers during pregnancy, childbirth, and the postpartum period. Autonomy in decision making was negatively correlated with birth-related PTSD symptoms, r=-.43, p < .01. An interaction between autonomy in decision making and mistreatment by providers was trending toward significance, B=-.23, SE=.14, p = .10. Autonomy in decision making and feeling respected by maternity care provider interacted to predict birth-related PTSD symptoms, B = .05, SE=.01, p < .01. Feeling respected by providers may buffer against the negative effects of lack of autonomy in decision making on birth-related PTSD symptoms, highlighting the importance of providers' ability to convey respect to pregnant patients when they cannot lead care decisions.

Inflammation, amygdala-ventromedial prefrontal functional connectivity and symptoms of anxiety and PTSD in African American women recruited from an inner-city hospital: Preliminary results.

Inflammatory stimuli have been shown to impact brain regions involved in threat detection and emotional processing including amygdala and ventromedial prefrontal cortex (vmPFC), and to increase anxiety. Biomarkers of endogenous inflammation, including inflammatory cytokines and C-reactive protein (CRP), are reliably elevated in a subset of patients with depression and anxiety-related disorders such as post-traumatic stress disorder (PTSD), and have been associated with high anxiety in population studies. We previously reported that plasma CRP and cytokines in patients with depression were negatively correlated with resting-state functional connectivity (FC) between right amygdala and vmPFC, as assessed using both ROI to voxel-wise and targeted FC approaches, in association with symptoms of anxiety, particularly in patients with comorbid anxiety disorders or PTSD. To determine whether relationships between inflammation, right amygdala-vmPFC FC, and anxiety are reproducible across patient samples and research settings, we employed an a priori, hypothesis-driven approach to examine relationships between inflammation, targeted right amygdala-vmPFC FC and anxiety in a cohort of African American (AA) women (n = 54) recruited from an inner-city hospital population reliably found to have higher levels of inflammation (median CRP âˆ¼ 4 mg/L) as well as symptoms of anxiety, depression and PTSD. Higher concentrations of plasma CRP were associated with lower right amygdala-vmPFC FC (r = -0.32, p = 0.017), and this relationship remained significant when controlling for age, body mass index and number of lifetime trauma events experienced, as well as severity of PTSD and depression symptoms (all p < 0.05). This amygdala-vmPFC FC was similarly associated with a composite score of three inflammatory cytokines in a subset of women where plasma was available for analysis (n = 33, r = -0.33, p = 0.058; adjusted r = -0.43, p = 0.026 when controlling for covariates including PTSD and depression symptom severity). Lower right amygdala-vmPFC FC was in turn associated with higher levels of anxiety reported to be generally experienced on the State-Trait Anxiety Inventory, trait component (adjusted r = -0.32, p = 0.039 when controlling for covariates). Exploratory analyses also revealed a negative correlation between severity of childhood maltreatment and right amygdala-vmPFC FC (r = -0.32, p = 0.018) that was independent of CRP and its association with FC, as well as an association between low amygdala-vmPFC FC and severity of PTSD symptoms, specifically the re-experiencing/intrusive symptom subscale (adjusted r = -0.32, p = 0.028 when controlling for covariates). While CRP was not linearly associated with either anxiety or PTSD symptoms, CRP concentrations were higher in women reporting clinically significant anxiety or PTSD symptom severity when these symptoms were considered together (both p < 0.05), but with no interaction. These results support our primary hypothesis that higher inflammation was associated with lower amygdala-vmPFC FC, a relationship that was detected using a hypothesis-driven, targeted approach. Findings also support that this phenotype of high CRP and low vmPFC FC was observed in association with anxiety in primary analyses, as well as symptoms of PTSD in exploratory analyses, in a cohort recruited from an inner-city population of AA women enriched for high inflammation, history of trauma exposure, and symptom severity. Larger, longitudinal samples are required to fully tease apart causal relationships between inflammatory biomarkers, FC and PTSD-related symptoms in future studies.

The relations between C-reactive protein and trauma exposure, PTSD and depression symptoms, and PTSD psychotherapy treatment response in treatment seeking veterans and service members.

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.

Neuroendocrine pathways underlying risk and resilience to PTSD in women.

Women are twice as likely than men to suffer from posttraumatic stress disorder (PTSD). While women have increased exposure to traumatic events of many types and have greater prevalence of comorbid psychiatric disorders compared to men, these differences do not account for the overall sex difference in the prevalence of PTSD. The current review summarizes significant findings that implicate the role of estradiol, progesterone, and allopregnanolone in female risk for PTSD symptoms and dysregulation of fear psychophysiology that is cardinal to PTSD. We also discuss how these steroid hormones influence the stress axis and neural substrates critical for the regulation of fear responses. Understanding the role of ovarian steroid hormones in risk and resilience for trauma-related adverse mental health outcomes across the lifespan in women has important translational, clinical, and intergenerational implications for mitigating the consequences of trauma exposure.

Indirect effect of negative evaluations of therapy on the association between racial stress and posttraumatic stress disorder symptoms in pregnant Black persons.

OBJECTIVE: Black pregnant individuals are at disproportionate risk for posttraumatic stress disorder (PTSD) compared to other groups. A wealth of literature suggests racial stress contributes to this inequity, but cultural and structural mechanisms, such as perceived barriers to mental health treatment, underlying the relationship between racial stress and PTSD symptoms remain understudied. Negative evaluations of psychotherapy and stigma represent potential mechanisms, though no previous studies have examined these associations. To address this gap, we tested an indirect effect of racial stress on PTSD symptoms through perceived barriers to mental health treatment in pregnant Black individuals. METHOD: Mediation analyses were used to assess an indirect relationship between racial stress and PTSD symptoms through perceived barriers to mental health treatment. RESULTS: At the bivariate level, racial stress was significantly associated with PTSD symptoms (r = .20, p = .03) and negative evaluations of therapy (r = .22, p = .02), but not with stigma (r = .140, p = .147). Negative evaluations of therapy were also associated with PTSD symptoms (r = .43, p < .001). There was an indirect effect of racial stress on PTSD symptoms through a negative evaluation of therapy, ß = .08, SE = 0.04, CI [0.01, 0.18]. More specifically, racial stress was associated with a more negative evaluation of therapy, which was in turn associated with more PTSD symptoms. CONCLUSIONS: Results highlight the need for accessible and culturally competent mental health care for pregnant Black individuals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Relations Among Childhood Maltreatment and Later Intimate Partner Violence Victimization With and Without a Weapon in a Sample of Pregnant Black Individuals.

Black pregnant and postpartum individuals are at risk for intimate partner violence (IPV), and those with a history of childhood maltreatment and IPV are even more likely to be re-victimized during pregnancy. However, it is unknown if specific types of child maltreatment predict later IPV with and without a weapon better than others. The current study sought to (i) document the prevalence of childhood maltreatment and IPV and (ii) examine the relations among types of childhood maltreatment and later IPV with and without a weapon within a sample of Black individuals seeking prenatal care at a large public hospital in the southeastern United States. Participants (n = 186; mean age = 27.2 years, SD = 5.3) completed measures assessing childhood maltreatment and IPV with and without a weapon. Approximately 68.5% of participants (n = 124) endorsed experiencing childhood maltreatment, while 42.6% (n = 78) endorsed experiencing IPV. The bivariate relations among five childhood maltreatment types (i.e., sexual, physical, and emotional abuse, physical and emotional neglect) and IPV with and without a weapon were assessed. All childhood maltreatment subtype scores-except childhood physical neglect-were significantly higher among participants who reported a history of IPV with or without a weapon compared to participants who denied a history of IPV with or without a weapon. Logistic regression models revealed childhood sexual abuse emerged as the only significant predictor of experiencing IPV with a weapon (B = 0.10, p = .003) and IPV without a weapon (B = 0.11, p = .001). For every point increase in childhood sexual abuse subtype score, the odds of experiencing IPV with and without a weapon increased by 10% (OR = 1.10, 95%CI [1.04, 1.18]) and 12% (OR = 1.12, [1.05, 1.20]), respectively. Findings suggest that screening for childhood sexual abuse may provide a critical opportunity for maternity care providers to identify individuals at increased risk for IPV victimization with and without a weapon.

Neighborhood Poverty Prospectively Predicts PTSD Symptoms Six-Months Following Trauma Exposure.

Introduction: Individuals living in areas with high rates of poverty are disproportionately affected by posttraumatic stress disorder (PTSD). Despite this association, little is known about how neighborhood poverty rates impact risk for PTSD development. In the current prospective study, we determined the relationship between neighborhood poverty rate and PTSD symptoms six-months after experiencing a traumatic event in a sample of varied race, gender, and socioeconomic status. Methods: Participants (N=252) were enrolled in a hospital emergency department after experiencing a traumatic event. Demographic information (including zip code of residence), baseline PTSD symptoms, and baseline trauma history was assessed in the emergency department. PTSD symptoms were again assessed six-months post-trauma. Neighborhood poverty rate was determined using the American Community Survey. Results: Correlation analyses revealed that neighborhood poverty was significantly associated with baseline PTSD symptoms (r=.181, p=.004) and PTSD symptoms six-months post-trauma (r=.163, p=.009). A regression analysis controlling for baseline trauma exposure, clinician-rated trauma severity, and individual socioeconomic status demonstrated that neighborhood poverty predicted PTSD symptoms six-months post-trauma (R2= 0.099, B= 0.15, p=0.04), but this relationship was no longer significant when baseline PTSD symptoms was added as an additional covariate (R2=.304, B= 0.07, p>0.05). Conclusion: Overall, results suggest that neighborhood poverty generally increases PTSD symptom severity, and the context in which an individual lives should be considered when conceptualizing risk for PTSD.

Intersections of oppression: Examining the interactive effect of racial discrimination and neighborhood poverty on PTSD symptoms in Black women.

Black Americans living in urban environments are disproportionately impacted by posttraumatic stress disorder (PTSD). Both racial discrimination and neighborhood poverty are factors that contribute to this health disparity. However, studies focused on the intersection of these two oppressive systems on PTSD symptoms are lacking. To address this gap in the literature, we assessed the interactive effects of racial discrimination and neighborhood poverty on PTSD symptoms in an urban sample of trauma-exposed Black women (N = 300). Simple moderation analysis was used to assess the main and interactive effects of racial discrimination and neighborhood poverty on PTSD symptoms. The overall model significantly predicted PTSD symptoms, with a main effect of racial discrimination (B = 1.87, p = .009) and neighborhood poverty rate (B = 0.29, p = .008), independent of prior trauma exposure and percentage of Black residents in the zip code. More frequent experiences of racial discrimination and higher rates of neighborhood poverty both predicted higher PTSD symptoms. There was also a trending interaction of racial discrimination and neighborhood poverty (B = -0.05, p = .054), where the effect of neighborhood poverty on PTSD symptoms was only present for those who reported fewer experiences of racial discrimination. Our results suggest that people who have experienced more instances of racial discrimination show high levels of PTSD symptoms regardless of neighborhood poverty rates and highlight the importance of considering multiple levels of oppression that Black individuals face while diagnosing and treating stress-related psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Stress-Related Mental Health Disorders and Inflammation in Pregnancy: The Current Landscape and the Need for Further Investigation.

Many studies have focused on psychoimmunological mechanisms of risk for stress-related mental health disorders. However, significantly fewer studies have focused on understanding mechanisms of risk for stress-related disorders during pregnancy, a period characterized by dramatic changes in both the innate and adaptive immune systems. The current review summarizes and synthesizes the extant literature on the immune system during pregnancy, as well as the sparse existing evidence highlighting the associations between inflammation and mood, anxiety, and fear-related disorders in pregnancy. In general, pregnant persons demonstrate lower baseline levels of systemic inflammation, but respond strongly when presented with an immune challenge. Stress and trauma exposure may therefore result in strong inflammatory responses in pregnant persons that increases risk for adverse behavioral health outcomes. Overall, the existing literature suggests that stress, trauma exposure, and stress-related psychopathology are associated with higher levels of systemic inflammation in pregnant persons, but highlight the need for further investigation as the existing data are equivocal and vary based on which specific immune markers are impacted. Better understanding of the psychoimmunology of pregnancy is necessary to reduce burden of prenatal mental illness, increase the likelihood of a successful pregnancy, and reduce the intergenerational impacts of prenatal stress-related mental health disorders.

The Immunology of Stress and the Impact of Inflammation on the Brain and Behavior.

Exposure to acute versus chronic stressors and threats activates the immune system in adaptive and maladaptive manners, respectively. While acute activation of the immune system in response to threat is homeostatically regulated by glucocorticoid negative feedback, chronic activation of the immune system arising from persistent stress exposure can contribute to an allostatic load with an inflammatory diathesis that has been implicated in stress-related psychopathology, including of depression and anxiety. Increased inflammation in the periphery and in the brain arising from chronic stress exposure can alter neurotransmitter metabolism and impact activation of brain regions to increase adverse behavioral health symptoms (e.g. anhedonia, anxiety, fatigue) and emotion dysregulation. While interventions targeting the immune system and its downstream effects on the brain for the treatment of depression and other psychiatric disorders has been of great interest as they have shown some efficacy in treating stress-related behavioral health disorders, future studies are necessary to better characterize the contexts under which anti-inflammatory agents should be used to treat stress-related psychopathology.

Hippocampal activation during contextual fear inhibition related to resilience in the early aftermath of trauma.

BACKGROUND: Impaired contextual fear inhibition is often associated with posttraumatic stress disorder (PTSD). Our previous work has demonstrated that more hippocampal activation during a response inhibition task after trauma exposure was related to greater resilience and fewer future PTSD symptoms. In the current study, we sought to extend our previous findings by employing a contextual fear conditioning and extinction paradigm to further determine the role of the hippocampus in resilience and PTSD in the early aftermath of trauma. METHODS: Participants (N = 28) were recruited in the Emergency Department shortly after experiencing a traumatic event. A contextual fear inhibition task was conducted in a 3 T MRI scanner approximately two months post-trauma. Measures of resilience (CD-RISC) at time of scan and PTSD symptoms three months post-trauma were collected. The associations between hippocampal activation during fear conditioning and during the effect of context during extinction, and post-trauma resilience and PTSD symptoms at three-months were assessed. RESULTS: During fear conditioning, activation of the bilateral hippocampal region of interest (ROI) correlated positively with resilience (r = 0.48, p = 0.01). During the effect of context during extinction, greater bilateral hippocampal activation correlated with lower PTSD symptoms three months post-trauma after controlling for baseline PTSD symptoms, age and gender (r=-0.59, p=0.009). CONCLUSIONS: Greater hippocampal activation was related to post-trauma resilience and lower PTSD symptoms three months post-trauma. The current study supports and strengthens prior findings suggesting the importance of hippocampus-dependent context processing as a mechanism for resilience versus PTSD risk, which could be a potential mechanistic target for novel early interventions.