To mark 15 years of the European Journal of Psychotraumatology, editors reviewed the past 15-year years of research on trauma exposure and its consequences, as well as developments in (early) psychological, pharmacological and complementary interventions. In all sections of this paper, we provide perspectives on sex/gender aspects, life course trends, and cross-cultural/global and systemic societal contexts. Globally, the majority of people experience stressful events that may be characterized as traumatic. However, definitions of what is traumatic are not necessarily straightforward or universal. Traumatic events may have a wide range of transdiagnostic mental and physical health consequences, not limited to posttraumatic stress disorder (PTSD). Research on genetic, molecular, and neurobiological influences show promise for further understanding underlying risk and resilience for trauma-related consequences. Symptom presentation, prevalence, and course, in response to traumatic experiences, differ depending on individuals' age and developmental phase, sex/gender, sociocultural and environmental contexts, and systemic socio-political forces. Early interventions have the potential to prevent acute posttraumatic stress reactions from escalating to a PTSD diagnosis whether delivered in the golden hours or weeks after trauma. However, research on prevention is still scarce compared to treatment research where several evidence-based psychological, pharmacological and complementary/ integrative interventions exist, and novel forms of delivery have become available. Here, we focus on how best to address the range of negative health outcomes following trauma, how to serve individuals across the age spectrum, including the very young and old, and include considerations of sex/gender, ethnicity, and culture in diverse contexts, beyond Western, Educated, Industrialized, Rich, and Democratic (WEIRD) countries. We conclude with providing directions for future research aimed at improving the well-being of all people impacted by trauma around the world. The 15 years EJPT webinar provides a 90-minute summary of this paper and can be downloaded here [http://bit.ly/4jdtx6k].

Background: Posttraumatic stress disorder (PTSD) is associated with metabolic syndrome and various addictive behaviours. Food addiction (FA) is associated with obesity, and individuals with PTSD have higher rates of FA than those without. It is unclear whether addictive-like eating patterns contribute to the metabolic dysfunction in PTSD.Objective: We examined the relative contributions of PTSD, FA, and sex - as well as their interactive effects - to the systemic inflammation (CRP) and metabolic syndrome components (MetS: waist circumference, glucose, triglycerides, HDL cholesterol, insulin) in a general population of the Upper Silesia region in Poland.Method: N = 187 participants (52.7% women) completed Yale Food Addiction Scale 2.0 (FA symptoms count), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) semi-structured interview (PTSD or other trauma and stressor-related disorder (OTSR) diagnosis presence), anthropometric assessment, and phlebotomy in a fasted state.Results: A series of hierarchical linear regressions indicated that greater number of FA symptoms had a significant effect on greater waist circumference, while PTSD/OTSR diagnosis had a significant effect on higher insulin levels. Sex did not moderate these relationships.Conclusions: It appears that dysregulated eating patterns are associated with greater abdominal obesity, but not with metabolic dysfunction. PTSD/OTSR, but not FA, contributes to greater insulin levels. The average metabolic indices were within normal limits reflecting a non-clinical nature of the sample. Future longitudinal studies should examine whether detection of and intervention for PTSD/OTSR symptoms may be a strategy for preventing progression of metabolic dysfunction.

The development of posttraumatic stress disorder (PTSD) is attributable to the interplay between exposure to severe traumatic events, environmental factors, and biological characteristics. Blood and brain imaging markers have been associated with PTSD. However, to our knowledge, no study has systematically investigated the genetic relationship between PTSD, metabolic biomarkers, and brainwide imaging.

We integrated genome-wide data informative of PTSD, 233 metabolic biomarkers, and 3935 brain imaging-derived phenotypes (IDPs). Pleiotropy was assessed by applying global and local genetic correlation, colocalization, and genetically inferred causality.

We observed significant genetic overlap between PTSD and glycoprotein acetyls (GlycA) (a stable inflammatory biomarker) in 2 independent cohorts (discovery r g = 0.26, p = 1.00 × 10-4; replication r g = 0.23, p = 5.99 × 10-19). Interestingly, there was no genetic correlation between anxiety and GlycA (p = .33). PTSD and GlycA were both genetically correlated with median T2∗ in the left pallidum (IDP-1444: r g = 0.14, p = 1.39 × 10-5; r g = -0.38, p = 2.50 × 10-3, respectively). Local genetic correlation between PTSD and GlycA was observed in 7 genetic regions (p < 2.0 × 10-5), mapping genes related to immune and stress response, inflammation, and metabolic processes. Furthermore, we identified 1 variant, rs12048743, with evidence of horizontal pleiotropy linking GlycA and IDP-1444 (z IDP-1444 = 17.14, z GlycA = -6.07, theta p = 2.06 × 10-8). Regional colocalization was observed among GlycA, IDP-1444, and tissue-specific transcriptomic regulation for brain frontal cortex and testis (rs12048743-chr1q32.1; posterior probability > 0.8). While we also tested causality between PTSD, metabolomic biomarkers, and brain IDPs, these were not consistent across different genetically informed causal inference methods.

Our findings highlight a new putative pleiotropic mechanism that links systemic inflammation and pallidum structure to PTSD.

Post-traumatic stress disorder (PTSD) is a heterogeneous mental health condition, characterized by diverse symptom profiles and biological underpinnings. A dissociative subtype of PTSD has been identified, though the potential risk factors and underlying neurobiology are yet to be understood. The current study comprised Canadian Armed Forces (CAF) members and Veterans with a history of deployment, and with diagnoses of non-dissociative (n = 31) and dissociative subtypes of PTSD (n = 19), in addition to non-deployed healthy controls (n = 14). Participants completed questionnaires assessing clinical symptoms and experiences of trauma, and provided saliva and blood samples for cortisol and inflammatory marker assessments. Individuals with dissociative PTSD displayed elevated PTSD and depression symptom severity, and greater reports of specific forms of childhood trauma compared to individuals with non-dissociative PTSD and controls. Morning cortisol was elevated in both PTSD groups compared to controls, however the PTSD groups did not differ from one another. Evening cortisol concentrations were elevated in both PTSD groups compared to controls, and in the dissociative PTSD subtype compared to the non-dissociative PTSD subtype when controlling for depression symptoms. PTSD diagnostic group moderated the relationship between awakening cortisol levels and PTSD symptom severity, such that the non-dissociative PTSD group displayed a negative correlation between awakening cortisol levels and PTSD symptom severity, while no significant relation was identified in the dissociative PTSD group. C-reactive protein (CRP) levels did not differ across diagnostic groups when accounting for body mass index (BMI). However, CRP positively correlated with depressive symptoms only among individuals with dissociative PTSD. Together, examining PTSD subtypes may help inform more effective and personalized treatment strategies in the future.

Targeting the immune system has recently garnered attention in the treatment of stress- associated psychiatric disorders resistant to existing pharmacotherapeutics. While such approaches have been studied in considerable detail in depression, the role of (neuro)inflammation in anxiety-related disorders, or in anxiety as an important transdiagnostic symptom, is much less clear. In this review we first critically review clinical and in part preclinical evidence of central and peripheral immune dysregulation in anxiety disorders and post-traumatic stress disorder (PTSD) and briefly discuss proposed mechanisms of how inflammation can affect anxiety-related symptoms. We then give an overview of existing and potential future targets in inflammation-associated signal transduction pathways and discuss effects of different immune-modulatory drugs in anxiety-related disorders. Finally, we discuss key gaps in current clinical trials such as the lack of prospective studies involving anxiety patient stratification strategies based on inflammatory biomarkers. Overall, although evidence is rather limited so far, there is data to indicate that increased (neuro)inflammation is present in subgroups of anxiety disorder patients. Although exact identification of such immune subtypes of anxiety disorders and PTSD is still challenging, these patients will likely particularly benefit from therapeutic targeting of aspects of the inflammatory system. Different anti-inflammatory treatment approaches (microglia-directed treatments, pro-inflammatory cytokine inhibitors, COX-inhibitors, phytochemicals and a number of novel anti-inflammatory agents) have indeed shown some efficacy even in non-stratified anxiety patient groups and appear promising as novel alternative or complimentary therapeutic options in specific ("inflammatory") subtypes of anxiety disorder and PTSD patients.

ObjectivePaediatric intensive care unit (PICU) admission represents a traumatic event for many children. Follow-up studies have found post-traumatic stress disorder (PTSD) rates of 10-30%, with a particular prevalence following admission for sepsis. Dysregulated inflammatory responses are associated with PTSD. Sepsis involves a marked inflammatory response but the relationship between this and PTSD have not been clearly established. In this study we investigate associations between the inflammatory response, psychosocial risk factors, and PTS symptoms following PICU admission for septic shock.We investigate the outcomes for children aged > 3 years, discharged from one PICU following admission for septic shock between 2010 and 2017. The study was a retrospective analysis of PICU-specific PTS symptoms reported by parents at any time since discharge via the Trauma and Behavior Health screen. Demographics, pre-morbid health characteristics, and exposure to other traumatic events were assessed. Clinical characteristics and blood test results at admission and at 48 h were recorded from clinical records. Multiple linear regression was used to investigate relationships between PTS symptom scores and predictor variables.Data for 65 participants (48% male, median assessment age 8.0 years) was available. Median time since admission was 5.1 years. 30.8% children scored at risk of PTSD at any time since discharge Symptoms were significantly associated with acute CRP rise (p 0.03), other trauma exposures (p = 0.01), and female gender (p =0.04).PTS symptoms in children who have survived septic shock are prevalent. These findings support a possible contribution of acute inflammatory changes, cumulative traumatic exposure, and female gender in post-PICU PTSD development.

As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders. Nature has equipped the cells, the organs, and the individuals with mediators and mechanisms that allow them to deal with stress, and even a good stress (eustress) has been associated with homeostasis. Likewise, societies and the planet are exposed to stressful settings, but wars and global warming suggest that the regulatory mechanisms are poorly efficient. In this review we list some inducers of the physiological stress, psychologic stress, societal stress, and planetary stress, and mention some of the great number of parameters which affect and modulate the response to stress and render it different from an individual to another, from the cellular level to the societal one. The cell, the organ, the individual, the society, and the planet share many stressors of which the consequences are extremely interconnected ending in the domino effect and the butterfly effect.

Depression and anxiety are linked to deep venous thrombosis (DVT) and posttraumatic disorder (PTSD) increases risk of venous thromboembolism in women. However, the mechanisms underlying this relationship remain unknown. We hypothesized that PTSD would associate with increased DVT risk, that neuroimmune mechanisms would mediate the PTSD-DVT link, and that these associations would be stronger in women. This cohort study included N = 106 427 participants from a large biobank. PTSD and DVT were defined using ICD-10 codes. A subset (N = 1520) underwent imaging, from which we assessed stress-associated neural activity (SNA). High-sensitivity C-reactive protein (hs-CRP) levels and heart rate variability (HRV) were used as indicators of systemic inflammation and autonomic activity, respectively. Linear, logistic, and Cox regressions and mediation analyses were used to test our hypotheses. Of 106 427 participants, 4192 (3.9%) developed DVT. PTSD associated with increased DVT risk (HR [95% CI]: 1.66 [1.34, 2.07], p < .001), and this finding remained significant after adjustment for age, sex, and traditional DVT risk factors. When analyzed separately by sex, PTSD was significantly associated with DVT risk in women but not men. Further, heightened SNA and lower HRV mediated the effect of PTSD on DVT risk. Results suggest that individuals with PTSD are at increased risk for DVT, and that risk is higher in women. This relationship was partially driven by alterations in stress-associated neural activity and autonomic function, suggesting potential targets for preventive therapies. Future studies are needed to investigate whether intervening on PTSD-DVT mechanisms has downstream beneficial effects on DVT, especially among women.

Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.

Understanding biological pathways that mediate trauma-related psychopathology is a major goal for traumatic stress studies. There is growing interest in studying differences in neural, physiological, and behavioral correlates of traumatic stress across demographic groups (e.g., sex/gender, race/ethnicity). However, challenges remain in how to appropriately conceptualize the source, mechanisms, and practical utility of between-group variation. The present brief conceptual review discusses ethnicity, race, and sex/gender-related variability relevant to understanding the psychobiology of traumatic stress in the context of traumatic stress studies. We discuss recent evidence related to socioenvironmental influences on ethnoracial variability in the brain and behavior relevant to traumatic stress, as well as sex/gender associations in neurophysiology that may contribute to the development of adverse posttraumatic sequelae. We further synthesize these findings by discussing intersectional influences of sex/gender- and race/ethnicity-related factors on trauma-related physical and mental health outcomes. The present review provides an important foundation for future research on disparities and individual differences in traumatic stress to move the field toward more effective assessment and treatment approaches.

Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder associated with adverse long-term health outcomes, including cardiovascular disease (CVD). Despite growing evidence that PTSD is positively associated with CVD, the biological mechanisms underlying this association are poorly understood. This review provides an overview of the current state of science on the genetic association between PTSD and CVD.

This scoping review identified studies from Pubmed, Embase, PsycINFO, and Web of Science. The search terms were a combination of PTSD, CVD/CVD-related traits, and a set of genetic molecules and related terms. This review followed the PRISMA Extension for Scoping Reviews guidelines. Eligible criteria included original studies that have genetic factors related to PTSD or CVD, conducted in humans, written in English, and published between 2003 and 2023 in peer-reviewed journals.

A total of twenty-three studies were included; PTSD correlated with genetic variants in CVD-related traits and gene expression in regulatory pathways contributing to CVD development. Common CVD-related traits involved in genetic associations with PTSD were inflammation, cellular aging, increased blood pressure, hypothalamus-pituitary-adrenal axis dysregulation, metabolic syndrome, and oxidative stress. These traits may explain potential underlying mechanisms between PTSD and CVD. Evidence of a causal relationship between the two diseases was insufficient.

PTSD and CVD/CVD-related traits are genetically associated. Further research is needed to comprehensively explore gene-environment interactions and the cumulative impact of behavioral and psychological factors on the pathophysiological mechanisms between PTSD and CVD.

Gestational metabolic diseases adversely impact the health of pregnant persons and their offspring. Pregnant persons of color are impacted disproportionately by gestational metabolic disease, highlighting the need to identify additional risk factors contributing to racial-ethnic pregnancy-related health disparities. Trauma exposure and posttraumatic stress disorder (PTSD) are associated with increased risk for cardiometabolic disorders in nonpregnant persons, making them important factors to consider when identifying contributors to gestational metabolic morbidity and mortality health disparities. Here, we review current literature investigating trauma exposure and posttraumatic stress disorder as psychosocial risk factors for gestational metabolic disorders, inclusive of gestational diabetes, low birth weight and fetal growth restriction, gestational hypertension, and preeclampsia. We also discuss the physiological mechanisms by which trauma and PTSD may contribute to gestational metabolic disorders. Ultimately, understanding the biological underpinnings of how trauma and PTSD, which disproportionately impact people of color, influence risk for gestational metabolic dysfunction is critical to developing therapeutic interventions that reduce complications arising from gestational metabolic disease. KEY POINTS: · Gestational metabolic diseases disproportionately impact the health of pregnant persons of color.. · Trauma and PTSD are associated with increased risk for cardiometabolic disorders in nonpregnant per.. · Trauma and PTSD impact physiological cardiometabolic mechanisms implicated in gestational metabolic..

Depression and multiple musculoskeletal disorders are overrepresented in women compared with men. Given that depression is a modifiable risk factor and improvement of depressive symptoms increases positive outcomes following orthopedic intervention, efforts to improve clinical recognition of depressive symptoms and increased action toward ameliorating depressive symptoms among orthopedic patients are positioned to reduce complications and positively affect patient-reported outcomes. Although psychosocial factors play a role in the manifestation and remittance of depression, it is also well appreciated that primary biochemical changes are capable of causing and perpetuating depression. Unique insight for novel treatments of depression may be facilitated by query of the bidirectional relationship between musculoskeletal health and depression. This Review aims to synthesize the diverse literature on sex, depression, and orthopedics and emphasize the potential for common underlying biological substrates. Given the overrepresentation of depression and musculoskeletal disorders among women, increased emphasis on the biological drivers of the co-occurrence of these disorders is positioned to improve women's health.

Dynamic brain immune function in individuals with posttraumatic stress disorder is rarely studied, despite evidence of peripheral immune dysfunction. Positron emission tomography brain imaging using the radiotracer [11C]PBR28 was used to measure the 18-kDa translocator protein (TSPO), a microglial marker, at baseline and 3 h after administration of lipopolysaccharide (LPS), a potent immune activator. Data were acquired in 15 individuals with PTSD and 15 age-matched controls. The PTSD group exhibited a significantly lower magnitude LPS-induced increase in TSPO availability in an a priori prefrontal-limbic circuit compared to controls. Greater anhedonic symptoms in the PTSD group were associated with a more suppressed neuroimmune response. In addition, while a reduced granulocyte-macrophage colony-stimulating factor response to LPS was observed in the PTSD group, other measured cytokine responses and self-reported sickness symptoms did not differ between groups; these findings highlight group differences in central-peripheral immune system relationships. The results of this study provide evidence of a suppressed microglia-mediated neuroimmune response to a direct immune system insult in individuals with PTSD that is associated with the severity of symptoms. They also provide further support to an emerging literature challenging traditional concepts of microglial and immune function in psychiatric disease.

Although post-traumatic stress disorder (PTSD) and depression screening are recommended for traumatic injury patients, routine screening is still uncommon. Salivary inflammatory biomarkers have biological plausibility and potential feasibility and acceptability for screening. This study tested prospective associations between several salivary inflammatory biomarkers (proinflammatory cytokines interleukin-1β, interleukin-6, tumor necrosis factor-α; and C-reactive protein), collected during hospitalization and PTSD and depressive symptoms at 5-month follow-up.

Adult traumatic injury patients (N = 696) at a major urban Level 1 trauma center provided salivary samples and completed PTSD and depressive symptom measures during days 0-13 of inpatient hospitalization. At 5-month follow-up, 368 patients (77 % male, 23 % female) completed the Clinician-Administered PTSD Scale for DSM-IV and the Self-rated Inventory of Depressive Symptomatology. Analyses focused on a latent inflammatory cytokine factor and C-reactive protein at baseline predicting 5-month PTSD and depression symptom outcomes and included baseline symptom levels as covariates.

A latent factor representing proinflammatory cytokines was not related to 5-month PTSD or depressive symptom severity. Higher salivary CRP was related to greater PTSD symptom severity (β = .10, p = .03) at 5-month follow-up and more severity in the following depressive symptoms: changes in weight and appetite, bodily complaints, and constipation/diarrhea (β's from .14 to .16, p's from .004 -.03).

In a primarily Latine and Black trauma patient sample, salivary CRP measured after traumatic injury was related to greater PTSD symptom severity and severity in several depressive symptom clusters. Our preliminary findings suggest that salivary or systemic CRP may be useful to include in models predicting post-trauma psychopathology.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Significant morbidity and mortality from COVID-19-related illnesses have been observed among people of color within the United States. While theories involving healthcare inequity and political division have emerged to explain this observation, the role of chronic stress and inflammation is also being explored. Toxic stress is experienced disproportionately by race, ethnicity, and socioeconomic status and increases frailty and vulnerability to diseases such as COVID-19. C-reactive protein (CRP) is a biomarker associated with the inflammatory response that is typically elevated due to exposure to acute or chronic traumatic stress, as well as COVID-19. This study explored the relationship between CRP and Hispanic/non-Hispanic ethnicity among adults hospitalized with COVID-19 via a secondary analysis of retrospective electronic health record (EHR) data collected from a community healthcare system in Southern California. A total of 1,744 cases representing hospitalized adults with COVID-19 were reviewed. Data were extracted from the EHR to reflect demographics, medical diagnoses, medications, CRP, and comorbidity burden. Frequencies, percentages, and measures of central tendency were assessed to understand the distribution of data. Associations were conducted using Pearson's r and the chi-square test of independence. Differences between groups were examined via independent samples t-tests. The sample was 52% Hispanic, 56% male, and the mean age was 62 years (SD = 16.1). The mean age of Hispanic cases was younger than non-Hispanic cases (p < .001, η = 0.289). Serum CRP was significantly higher in the Hispanic cases, with a high degree of association (p < .001, η = 0.472). In addition, higher CRP levels were significantly associated with the need for mechanical ventilation (p < .001, φc = 0.216). No significant relationships were found between CRP and age, body mass index (BMI), or comorbidity burden. Findings challenge the assumption that the disproportionate morbidity and mortality suffered by the Hispanic population due to COVID-19 was due to age, BMI, or comorbidities such as metabolic syndrome or heart disease. CRP in the Hispanic population should be further investigated to understand its relationship to chronic stress, frailty, and risk for COVID-19 in this population.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Exposure to interpersonal violence affects a significant number of individuals each year and further increases the risk for developing Posttraumatic Stress Disorder (PTSD). A growing body of research suggests that immune system dysfunction, in particular elevated inflammation, may contribute to the pathophysiology of PTSD. However, few studies have examined the neurobiological correlates of inflammation in women with PTSD using resting-state fMRI. The present study explored the relationship between pro-inflammatory cytokine levels, C-reactive protein (CRP), tumor necrosis factor alpha TNF-alpha), and interleukin-6 (IL-6), and resting-state functional connectivity patterns in three major cortical networks (default mode network (DMN), central executive network (CEN), and salience network (SN)) in a sample of women (N=18) exposed to interpersonal violence with PTSD. Results indicated that higher CRP levels were associated with stronger functional connectivity between the SN and visual areas, but weaker functional connectivity between the CEN and visual areas. These findings suggest that pro-inflammatory markers are related to connectivity of task-positive networks in women with PTSD. Further, our results provide evidence for potential neurobiological markers of inflammation in PTSD.

Post-traumatic stress disorder (PTSD) is one of the most widespread and disabling psychiatric disorders among combat veterans. Substantial interindividual variability in susceptibility to PTSD suggests the presence of different risk factors for this disorder. Twin and family studies confirm genetic factors as important risk factors for PTSD. In addition to genetic factors, epigenetic factors, especially DNA methylation, can be considered as a potential mechanism in changing the risk of PTSD. So far, many genetic and epigenetic association studies have been conducted in relation to PTSD. In genetic studies, many single nucleotide polymorphisms have been identified as PTSD risk factors. Meanwhile, the variations in catecholamines-related genes, serotonin transporter and receptors, brain-derived neurotrophic factor, inflammatory factors, and apolipoprotein E are the most prominent candidates. CpG methylation in the upstream regions of many genes is also considered a PTSD risk factor. Accurate identification of genetic and epigenetic changes associated with PTSD can lead to the presentation of suitable biomarkers for susceptible individuals to this disorder. This study aimed to delineate prominent genetic variations and epigenetic changes associated with post-traumatic stress disorder in military veterans who have experienced combat, focusing on genetic and epigenetic association studies.

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

Chronic systemic inflammation has been implicated in trauma exposure, independent of a psychiatric diagnosis, and in posttraumatic stress disorder (PTSD) and its highly comorbid conditions, such as metabolic syndrome (MetS). The present study used network analysis to examine the interacting associations between pro-inflammatory cytokines, posttraumatic stress (PTS) symptoms and symptom clusters, and individual components of MetS, in a cohort of 312 participants (n = 139 PTSD cases, n = 173 trauma-exposed controls). Pro-inflammatory cytokines were measured in serum samples using immunoturbidimetric and multiplex assays. Three network models were assessed, and the decision on which model to use was guided by network stability estimates and denseness. Weak negative associations were observed between interleukin one beta (IL-1β) and detachment (D6) and irritability (E1); tumour necrosis factor alpha (TNFα) and hypervigilance (E3); and C-reactive protein (CRP) and emotional cue reactivity (B4), which could be due to high cortisol levels present in a female-majority cohort. Network models also identified positive associations between CRP and waist circumference, blood pressure, and high-density lipoprotein cholesterol (HDL-C). The strongest association was observed between CRP and waist circumference, providing evidence that central obesity is an important inflammatory component of MetS. Some networks displayed high instability, which could be due to the small pool of participants with viable cytokine data. Overall, this study provides evidence for associations between inflammation, PTS symptoms and components of MetS. Future longitudinal studies measuring pro-inflammatory cytokines in the immediate aftermath of trauma are required to gain better insight into the role of inflammation in trauma-exposure and PTSD.

Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon.

Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed.

Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35-55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P = 0.036).

Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees.

Post-traumatic stress disorder (PTSD) is a complex psychological disorder that develops following exposure to traumatic events. PTSD is influenced by catalytic factors such as dysregulated hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter imbalances, and oxidative stress. Genetic variations may act as important catalysts, impacting neurochemical signaling, synaptic plasticity, and stress response systems. Understanding the intricate gene networks and their interactions is vital for comprehending the underlying mechanisms of PTSD. Focusing on the catalytic factors of PTSD is essential because they provide valuable insights into the underlying mechanisms of the disorder. By understanding these factors and their interplay, researchers may uncover potential targets for interventions and therapies, leading to more effective and personalized treatments for individuals with PTSD. The aforementioned gene networks, composed of specific genes associated with the disorder, provide a comprehensive view of the molecular pathways and regulatory mechanisms involved in PTSD. Through this study valuable insights into the disorder's underlying mechanisms and opening avenues for effective treatments, personalized interventions, and the development of biomarkers for early detection and monitoring are provided.

Posttraumatic stress disorder (PTSD) is a robust risk factor for suicide. Studies have suggested an association between suicide and elevated inflammatory markers, although such evidence in PTSD is scarce. Suicide risk, PTSD, and inflammatory molecules are all shown to be associated with childhood maltreatment and genetic factors.

We examined the association between suicidal ideation/risk and inflammatory markers in 83 civilian women with PTSD, and explored the possible influence of childhood maltreatment and inflammatory genes. Suicidal ideation and risk were assessed using the Beck Depression Inventory-II and the Mini-International Neuropsychiatric Interview. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire (CTQ). Blood levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and high-sensitivity tumor necrosis factor-α were measured. Genetic polymorphisms of CRP rs2794520 and IL6 rs1800796 were genotyped.

Suicidal ideation was significantly positively correlated with hsCRP (p = 0.002) and IL-6 (p = 0.015) levels. Suicide risk weighted score was significantly positively correlated with hsCRP (p = 0.016) levels. The risk alleles of CRP rs2794520 and IL6 rs1800796 leading to increased respective protein levels were dose-dependently associated with higher risk of suicide (p = 0.007 and p = 0.029, respectively). The CTQ total score was significantly correlated with suicidal ideation and risk, but not with inflammatory marker levels. Furthermore, a multivariate regression analysis controlling for PTSD severity and potential confounders revealed that rs2794520 and rs1800796, but not hsCRP or IL-6 levels, significantly predicted suicidal ideation (p < 0.001) and risk (p = 0.007), respectively.

Genetic variations within inflammatory genes might be useful in detecting PTSD patients at high risk of suicide.

Despite high rates of Post-Traumatic Stress Disorder (PTSD) in persons living with HIV (PLWH) and poor HIV-related health outcomes associated with PTSD, an effective evidence-based treatment for PTSD symptoms in PLWH does not exist. Negative reinforcement conceptual models posit that avoidant behavior (hallmark symptom of PTSD) demonstrated by PLWH with co-occurring PTSD can contribute to poor antiretroviral therapy (ART) adherence. However, research evaluating the impact of evidence-based treatment for PTSD among HIV infected populations on HIV outcomes is scarce. The Cognitive Processing Therapy (CPT) protocol is an evidence-based PTSD treatment that may address internalized stigma with targeted modifications and improve ART adherence and subsequent viral suppression through reduction of avoidant coping. This study will be the first pilot open-label randomized control trial (RCT) to test feasibility of an integrated evidence-based PTSD treatment (CPT) with an adherence intervention (Lifesteps) delivered in a Ryan White clinic to improve PTSD symptoms, adherence to ART, and retention in HIV care. Primary aims are to (1) conduct theater testing of the CPT and Lifesteps research protocol and evaluate acceptability (n = 12) and (2) deliver a modified CPT protocol (CPT-Lifesteps, or CPT-L) in 60 PLWH/PTSD exploring impact of CPT-L on PTSD symptoms and HIV outcomes compared to a Lifesteps + Standard of Care condition. This innovative research extends PTSD treatment approaches as a paradigm to reduce barriers to ART adherence. Findings of this innovative study are significant because they support the Undetectable = Untransmittable (U[bond, double bond]U) campaign and can help prevent the transmission of HIV infection through increased viral suppression.

Several studies investigated the role of inflammation in the etiopathogenesis of mood disorders. The aim of our cross-sectional study is evaluating baseline high-sensitivity C-reactive-protein (hsCRP) levels in a cohort of unipolar and bipolar depressive inpatients, in relation with psychopathological, temperamental and chronotype features.

Among 313 screened inpatients, we retrospectively recruited 133 moderate-to-severe depressive patients who were assessed for hsCRP levels, chronotype with Morningness-Eveningness Questionnaire (MEQ) and affective temperament with Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS).

The cross-sectional and retrospective design of the study, the small sample size, the exclusion of hypomanic, maniac and euthymic bipolar patients.

hsCRP levels were significantly higher among those with previous suicide attempt (p = 0.05), death (p = 0.018) and self-harm/self-injury thoughts (p = 0.011). Linear regression analyses, adjusted for all covariates, demonstrated that higher scores at the TEMPS-M depressive, while lower scores at the hyperthymic and irritable affective temperaments [F = 88.955, R² = 0.710, p < 0.001] and lower MEQ scores [F = 75.456, R² = 0.405, p < 0.001] statistically significantly predicted higher hsCRP.

Eveningness chronotype and a depressive affective temperament appeared to be associated with higher hsCRP levels during moderate-to-severe unipolar and bipolar depression. Further longitudinal and larger studies should better characterise patients with mood disorders by investigating the influence of chronotype and temperament.

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the coronavirus disease 2019 (COVID-19) pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south-central region of China, between January 1, 2018, and December 31, 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the prepandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the prepandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (β = 0.07, SE = 0.02, P = 1.35 × 10^-3 ) and higher hospital costs (β = 0.06, SE = 0.03, p = 0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID-19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics.

Many people experience traumatic events during their lives, but not all of them develop severe mental pathologies, characterized by high levels of anxiety that persists for more than a month after psychological trauma, such as posttraumatic stress disorder (PTSD). We used a single prolonged stress protocol in order to model PTSD in long-inbred C57BL/6 and wild-derived (house) female mice. The susceptibility of mice to single prolonged stress was assessed by behavior phenotyping in the Open Field and Elevated Plus Maze, the level of neuroinflammation in the hippocampus was estimated by real-time PCR to TNFα, IL-1β, IL-6, IL-10, Iba1 and GFAP, as well as immunohistochemical analysis of microglial morphology and mean fluorescence intensity for GFAP+ cells. The level of neurogenesis was analyzed by real-time PCR to Ki67, Sox2 and DCX as well as immunohistochemistry to Ki67. We showed that long-inbread C57BL/6 mice are more susceptible to a single prolonged stress protocol compared to wild-derived (house) mice. Stressed C57BL/6 mice demonstrated elevated expression levels of proinflammatory cytokines TNFα, IL-1β, and IL-6 in the hippocampus, while in house mice no differences in cytokine expression were detected. Expression levels of Iba1 in the hippocampus did not change significantly after single prolonged stress, however GFAP expression increased substantially in stressed C57BL/6 mice. The number of Iba+ cells in the dentate gyrus also did not change after stress, but the morphology of Iba+ microglia in C57BL/6 animals allowed us to suggest that it was activated; house mice also had significantly more microglia than C57BL/6 animals. We suppose that decreased microglia levels in the hippocampus of C57BL/6 compared to house mice might be one of the reasons for their sensitivity to a single prolonged stress. Single prolonged stress reduced the number of Ki67+ proliferating cells in the dentate gyrus of the hippocampus but only in C57BL/6 mice, not in house mice, with the majority of cells detected in the dorsal (septal) hippocampus in both. The increase in the expression level of DCX might be a compensatory reaction to stress; however, it does not necessarily mean that these immature neurons will be functionally integrated, and this issue needs to be investigated further.

An increasing number of studies have investigated the role of inflammation in psychiatric disorders, by demonstrating how an altered/dysfunctional immunological and inflammatory system may underpin a psychiatric condition. Particularly, several studies specifically investigated the role of a neuroinflammatory biomarker, named C-reactive protein (CRP), in psychiatric disorders. Overall, even though scientific literature so far published still does not appear definitive, CRP is more likely reported to be elevated in several psychiatric disorders, including schizophrenia, mood disorders, anxiety disorders and post-traumatic stress disorder. Moreover, a low-grade inflammation (CRP >3 mg/L) has been more likely observed in a subgroup of patients affected with a more severe psychopathological symptomatology, more treatment resistance and worst clinical mental illness course, strengthening the hypothesis of the need for a different clinical and prognostic characterization based on this concomitant neuroinflammatory predisposition. However, even though further research studies are needed to confirm this preliminary evidence, CRP may represent a potential clinical routine biomarker which could be integrated in the clinical routine practice to better characterize clinical picture and course as well as address clinicians towards a personalized treatment.

Stress exposure during early stages of life elevates the risk of developing psychopathologies and psychiatric illness in later life. The brain and immune system are not completely developed by birth and therefore continue develop after birth; this post birth development is influenced by several psychosocial factors; hence, early life stress (ELS) exposure can alter brain structural development and function. A growing number of experimental animal and observational human studies have investigated the link between ELS exposure and increased risk of psychopathology through alternations in the immune system, by evaluating inflammation biomarkers. Recent studies, including brain imaging, have also shed light on the mechanisms by which both the innate and adaptive immune systems interact with neural circuits and neurotransmitters, which affect psychopathology. Herein, we discuss the link between the experience of stress in early life and lifelong alterations in the immune system, which subsequently lead to the development of various psychiatric illnesses.

As a major public health problem, posttraumatic stress disorder (PTSD) has a substantial impact on individuals and society. The total excess economic burden of PTSD in the US is estimated to be more than $232.2 billion a year. Acupuncture is widely used in patients with PTSD, and an increasing number of studies have been undertaken to assess the efficacy and underlying mechanisms of acupuncture for the treatment of individuals with PTSD. However, there has not yet been a review that simultaneously elucidates the therapeutic efficacy and biological mechanisms of acupuncture. We wished to examine the efficacy and underlying mechanisms of acupuncture for the treatment of individuals with PTSD. We conducted this review in three sections as follows: a meta-analysis, an acupoint analysis, and mechanism research. PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI), WanFang Database, China Biology Medicine Database (CBM), Chinese Science and Technology Journals Database (VIP), and other databases were searched from 1 January 2012 to 27 November 2022. Based on the included studies, we first determined whether acupuncture is more effective than psychological treatment or pharmacological treatment for treating and improving the quality of life of individuals with PTSD by meta-analysis. Second, the most commonly used acupoints and parameters of acupuncture were summarized based on animal and clinical studies. Third, we attempt to summarize the current mechanisms of acupuncture in the treatment of PTSD. Finally, 56 acupoint analyses, eight meta-analyses, and 33 mechanistic studies were included. Acupuncture outperformed pharmacotherapy treatment in improving symptom scores by CAPS, HAMA, HAMD, PCL-C, and SCL-90 somatization for PTSD and outperformed psychotherapy treatment in improving symptom scores by CAPS PCL-C and HAMD, according to the meta-analysis. GV20 was the most frequently used acupuncture point in clinical studies and animal studies, with a 78.6% application rate. Acupuncture may be effective in treating PTSD by regulating the structure and components of several brain areas, regulating the neuroendocrine system, and involving signaling pathways. In conclusion, this finding indicates that acupuncture has promising potential for treating PTSD.

Posttraumatic stress disorder (PTSD) is a severe trauma and stress-related disorder associated with different somatic comorbidities, especially cardiovascular and metabolic disorders, and with chronic low-grade inflammation. Altered balance of the hypothalamic-pituitary-adrenal (HPA) axis, cytokines and chemokines, C-reactive protein, oxidative stress markers, kynurenine pathways, and gut microbiota might be involved in the alterations of certain brain regions regulating fear conditioning and memory processes, that are all altered in PTSD. In addition to the HPA axis, the gut microbiota maintains the balance and interaction of the immune, CNS, and endocrine pathways forming the gut-brain axis. Disbalance in the HPA axis, gut-brain axis, oxidative stress pathways and kynurenine pathways, altered immune signaling and disrupted homeostasis, as well as the association of the PTSD with the inflammation and disrupted cognition support the search for novel strategies for treatment of PTSD. Besides potential anti-inflammatory treatment, dietary interventions or the use of beneficial bacteria, such as probiotics, can potentially improve the composition and the function of the bacterial community in the gut. Therefore, bacterial supplements and controlled dietary changes, with exercise, might have beneficial effects on the psychological and cognitive functions in patients with PTSD. These new treatments should be aimed to attenuate inflammatory processes and consequently to reduce PTSD symptoms but also to improve cognition and reduce cardio-metabolic disorders associated so frequently with PTSD.

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as admission Glasgow Coma Scale [GCS] score 13-15) enrolled in TRACK-TBI, a prospective longitudinal study of level 1 trauma center patients. Plasma glial fibrillary acidic protein (GFAP) and serum high sensitivity C-reactive protein (hsCRP) were measured from blood collected within 24 h of injury. Two hundred and twenty-seven (19.9% of) patients had probable PTSD (PCL-5 score ≥ 33) at 6 months post-injury. GFAP levels were positively associated (Spearman's rho = 0.35, p < 0.001) with duration of posttraumatic amnesia (PTA). There was an inverse association between PTSD and (log)GFAP (adjusted OR = 0.85, 95% CI 0.77-0.95 per log unit increase) levels, but no significant association with (log)hsCRP (adjusted OR = 1.11, 95% CI 0.98-1.25 per log unit increase) levels. Elevated day-of-injury plasma GFAP, a biomarker of glial reactivity, is associated with reduced risk of PTSD after mTBI. This finding merits replication and additional studies to determine a possible neurocognitive basis for this relationship.

(1) Background: Affective distress can be triggered by aggressive stimuli with an unfavorable role for the individual. Some of the factors that lead to the development and evolution of a mental disorder can be genetic. The aim of this study is to determine some correlations between the human leukocyte antigen (HLA) genes and the affective distress profile (PDA). (2) Methods: A psychological assessment and testing tool for anxiety was applied to 115 people. The low-resolution HLA alleles of class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1 and HLA-DQB1) were identified by the PCR technique after DNA extraction from the blood. Depending on the PDA, the subjects were divided into two groups: a group with a low PDA and another one with a medium and high PDA. The IBM SPSS software was used to compare the frequency of HLA alleles between the two groups. (3) Results: The univariate analysis revealed a significant association of the HLA-A locus (A*01, A*30), HLA-B (B*08), and HLA-DRB1 (DRB1*11) with the low PDA group and of the HLA-A locus (A*32), HLA-B (B*52), and HLA-C (C*12) with the medium and high PDA group. (4) Conclusions: The present study highlighted potential associations between HLA alleles and anxiety disorders.

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 ∼ 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.