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Background: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. Methods: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. Results: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. Conclusions: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories. [ABSTRACT FROM AUTHOR]

The article discusses the genetic correlation in posttraumatic stress disorder (PTSD) and cardiometabolic disorder using a genome-wide association study. It mentions the meta-analysis research on the overlapping of genes and its genetic risk factor. Various research on the genetic linkage between PTSD and cardiovascular disease is also discussed.

Social subordination in female macaques represents a well-described model of chronic psychosocial stress. Additionally, a length polymorphism (5- HTTLPR) in the regulatory region of the serotonin (5- HT) transporter (5- HTT) gene ( SLC6A4) is present in rhesus macaques, which has been linked to adverse outcomes similar to that described in humans with an analogous 5- HTTLPR polymorphism. The present study determined the effects of social status and the 5- HTTLPR genotype on 5- HT1 A receptor binding potential (5- HT1 A BPND) in brain regions implicated in emotional regulation and stress reactivity in ovariectomised female monkeys, and then assessed how these effects were altered by 17β-oestradiol ( E2) treatment. Areas analysed included the prefrontal cortex [anterior cingulate ( ACC); medial prefrontal cortex (m PFC); dorsolateral prefrontal cortex; orbitofrontal prefrontal cortex], amygdala, hippocampus, hypothalamus and raphe nucleui. Positron emission tomography using p-[18 F] MPPF was performed to determine the levels of 5- HT1 A BPND under a non- E2 and a 3-week E2 treatment condition. The short variant (s-variant) 5- HTTLPR genotype produced a significant reduction in 5- HT1A BPND in the m PFC regardless of social status, and subordinate s-variant females showed a reduction in 5- HT1 A BPND within the ACC. Both these effects of 5- HTTLPR were unaffected by E2. Additionally, E2 reduced 5- HT1 A BPND in the dorsal raphe of all females irrespective of psychosocial stress or 5- HTTLPR genotype. Hippocampal 5- HT1 A BPND was attenuated in subordinate females regardless of 5- HTTLPR genotype during the non- E2 condition, an effect that was normalised with E2. Similarly, 5- HT1 A BPND in the hypothalamus was significantly lower in subordinate females regardless of 5- HTTLPR genotype, an effect reversed with E2. Taken together, the data indicate that the effect of E2 on modulation of central 5 HT1 A BPND may only occur in brain regions that show no 5- HTTLPR genotype-linked control of 5- HT1 A binding. [ABSTRACT FROM AUTHOR]

Highlights: [•] Social subordination alters GABAARs binding in estradiol-treated female monkeys. [•] Status effect on GABAAR is site specific, only seen in the prefrontal cortex. [•] CRH receptor antagonism reverses status differences in GABAAR binding. [•] Implicates the stress axis in the dysregulation of GABAAR in subordinate females. [•] Provides mechanism by which subordination alters the actions of estradiol. [ABSTRACT FROM AUTHOR]

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.., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

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., (© 2024 International Society for Traumatic Stress Studies.)

Background: Exposure to trauma across the life course may be associated with cardio-metabolic dysfunction during pregnancy; however, previous research has been inconsistent, particularly in highly exposed populations., Objectives: To estimate associations between types and timing (first occurrence) of trauma exposure and hypertension experienced during pregnancy in a safety-net hospital in Atlanta, Georgia, 2011-2022., Methods: Participants completed a 14-item trauma screener. We linked that information to data from the medical record on hypertension (including chronic hypertension, gestational hypertension or preeclampsia). We fit logistic regression models and used the estimates to calculate risk ratios for each trauma type and each critical window (0-9 years, 10-19 and 20+). We fit unadjusted models and adjusted for age, parity and education., Results: We included 704 individuals with a delivery within 12 months following screening. The majority (94%, 661) reported at least one traumatic event, most commonly witnessing violence (79.4%). Overall, 18% experienced gestational hypertension, 10.8% chronic hypertension and 11.9% preeclampsia. Among individuals who reported trauma, 31.5% screened positive for probable posttraumatic stress disorder and 30.9% for probable depression, compared to 0 and 2.3% among those without reported trauma. No trauma type (violence, witnessing violence, non-interpersonal or sexual assault) was associated with increased hypertensive risk, regardless of timing., Conclusions: In this sample with a high trauma and hypertension burden, trauma was not associated with an elevated risk of hypertension during pregnancy, despite a high burden of PTSD and depressive symptoms among people with trauma exposure., (© 2024 John Wiley & Sons Ltd.)

Borderline Personality Disorder (BPD) is characterized by rapidly shifting emotional, interpersonal, and behavioral symptoms, and is often co-morbid with mood and anxiety disorders. Females are more likely to be diagnosed with BPD than males and exhibit greater functional impairment. Hormonal fluctuations, particularly in estrogen levels, may influence the manifestation of BPD symptoms. Here we investigated the influence of estrogen-suppressing contraceptives on behavioral and functional difficulties in BPD. The analytical sample included 348 females ages 18-50 undergoing residential treatment for psychiatric disorders, with 131 having a BPD diagnosis. Patients were categorized based on their contraceptive method: 1) Estrogen-suppressing contraceptives (N=145) and 2) Naturally cycling (N=203). Interaction models tested the impact of estrogen-suppressing contraceptives on the relationship between BPD diagnosis and behavioral and functional difficulties at admission and discharge, assessed by the four Behavior and Symptom Identification Scale (BASIS-32) domains: difficulties in relationships, daily living, depression/anxiety, and impulsivity. Females with a BPD diagnosis were more likely to use estrogen-suppressing contraceptives compared to those without BPD (p=0.04). However, estrogen-suppressing contraceptive use was not associated with behavioral and functional difficulties at admission, discharge, or over time. Estrogen-suppressing contraceptives moderated the association between BPD diagnosis and difficulties in relationships (p=0.004), difficulties in daily living (p=0.01), and depression/anxiety symptoms (p=0.004). Patients with BPD expressed increased behavioral and functional difficulties at admission, discharge, and over time only if naturally cycling (p<0.003). Our findings suggest that estrogen-suppressing contraceptives may help to regulate the rapidly shifting emotional, interpersonal, and behavioral symptoms in females with BPD by stabilizing estrogen levels.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD., Methods: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men., Results: Women reported higher PTSD severity at 3-months post-trauma. Z -score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects., Conclusions: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Despite extensive research on sex/gender differences in posttraumatic stress disorder (PTSD), underlying mechanisms are still not fully understood. Here we present a systematic overview of three sex/gender-related risk pathways. We assessed 16 risk factors as well as 3-month PTSD severity in a prospective cohort study (n=2924) of acutely traumatized individuals and investigated potential mediators in the pathway between sex assigned at birth and PTSD severity using multiple mediation analysis with regularization. Six risk factors were more prevalent/severe in women, and none were more pronounced in men. Analyses showed that acute stress disorder, neuroticism, lifetime sexual assault exposure, anxiety sensitivity, and pre-trauma anxiety symptoms fully mediated and uniquely contributed to the relationship between sex assigned at birth and PTSD severity. Our results demonstrate different risk mechanisms for women and men. Such knowledge can inform targeted interventions. Our systematic approach to differential risk pathways can be transferred to other mental disorders to guide sex- and gender-sensitive mental health research., Competing Interests: Competing Interests Statement -Dr. Neylan has received research support from NIH, VA, and Rainwater Charitable Foundation, and consulting income from Jazz Pharmaceuticals. - In the last three years Dr. Clifford has received research funding from the NSF, NIH and LifeBell AI, and unrestricted donations from AliveCor Inc, Amazon Research, the Center for Discovery, the Gates Foundation, Google, the Gordon and Betty Moore Foundation, MathWorks, Microsoft Research, Nextsense Inc, One Mind Foundation, the Rett Research Foundation, and Samsung Research. Dr Clifford has financial interest in AliveCor Inc and Nextsense Inc. He also is the CTO of MindChild Medical and CSO of LifeBell AI and has ownership in both companies. These relationships are unconnected to the current work. - Dr. Germine receives funding from the National Institute of Mental Health (R01 MH121617) and is on the board of the Many Brains Project. Dr. Germine’s family also has equity in Intelerad Medical Systems, Inc. -Dr. Rauch reports grants from NIH during the conduct of the study; personal fees from SOBP (Society of Biological Psychiatry) paid role as secretary, other from Oxford University Press royalties, other from APP (American Psychiatric Publishing Inc.) royalties, other from VA (Veterans Administration) per diem for oversight committee, and other from Community Psychiatry/Mindpath Health paid board service, including equity outside the submitted work; other from National Association of Behavioral Healthcare for paid Board service; other from Springer Publishing royalties; and Leadership roles on Board or Council for SOBP, ADAA (Anxiety and Depression Association of America), and NNDC (National Network of Depression Centers). - Dr. Jones has no competing interests related to this work, though he has been an investigator on studies funded by AstraZeneca, Vapotherm, Abbott, and Ophirex. - Dr. Harte has no competing interest related to this work, though in the last three years he has received research funding from Aptinyx and Arbor Medical Innovations, and consulting payments from Indiana University and Memorial Sloan Kettering Cancer Center. - Dr. McLean served as a consultant for Walter Reed Army Institute for Research and for Arbor Medical Innovations. - In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences. - Dr. Koenen’s research has been supported by the Robert Wood Johnson Foundation, the Kaiser Family Foundation, the Harvard Center on the Developing Child, Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, the National Institutes of Health, One Mind, the Anonymous Foundation, and Cohen Veterans Bioscience. She has been a paid consultant for Baker Hostetler, Discovery Vitality, and the Department of Justice. She has been a paid external reviewer for the Chan Zuckerberg Foundation, the University of Cape Town, and Capita Ireland. She has had paid speaking engagements in the last three years with the American Psychological Association, European Central Bank. Sigmund Freud University – Milan, Cambridge Health Alliance, and Coverys. She receives royalties from Guilford Press and Oxford University Press. - The remaining authors declare no competing interests.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aggression is a costly public health problem with severe and multi-faceted negative consequences and thus, identifying factors that contribute to aggression, particularly in understudied populations, is necessary to develop more effective interventions to reduce the public health cost of aggression. The goal this study was to test whether difficulties regulating emotions moderated the association between posttraumatic stress disorder (PTSD) symptoms and aggression in a community sample of predominantly Black females with high levels of trauma exposure. Furthermore, we explored unique relations between PTSD symptom clusters and distinct subscales of difficulties regulating emotions and aggression. The sample included 601 community participants recruited from an urban public hospital. Symptoms were assessed using self-report measures including the Difficulties in Emotion Regulation Scale (DERS) and Behavioral Questionnaire-Short. Regression analyses were conducted using PTSD symptoms and total DERS to test their interaction as predictors for aggression (using BQ-Short). We found that higher levels of PTSD arousal symptoms and difficulty controlling impulses when upset were positively related to aggression. We also conducted an exploratory analysis to examine the association between PTSD symptom clusters using the Alternative Symptom Clusters hybrid model. The results suggest that some PTSD symptoms (externalizing behavior) and some emotion dysregulation processes (difficulties controlling impulses when upset), relate to aggression in independent, rather than multiplicative ways. These results offer insights for new directions of research that focuses on the independent association between specific emotion dysregulation processes and PTSD symptoms on aggression., (© 2024 Wiley Periodicals LLC.)

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., (© 2024. The Author(s).)

Background: The prevalence of posttraumatic stress disorder (PTSD) among people living with HIV (PLWH) is higher than in the general population and can impact health behaviors. The influence of HIV on PTSD psychophysiology requires further investigation due to implications for the treatment of PTSD in PLWH., Objective: Utilizing fear-potentiated startle (FPS), we aimed to interrogate the influence of PTSD and HIV on fear responses., Materials and Methods: Women (18-65 years of age) recruited from the Women's Interagency HIV Study in Atlanta, GA ( n  = 70, 26 without HIV and 44 with HIV), provided informed consent and completed a semistructured interview to assess trauma exposure and PTSD symptom severity. Participants also underwent an FPS paradigm to assess fear acquisition and extinction: Psychophysiological indices that measure how individuals learn new fear and then subsequently attempt to suppress this fear., Results: Women with PTSD, who did not have HIV, exhibited a greater startle response compared to women without PTSD or HIV during late acquisition to both the danger cue, reinforced conditioned stimulus (CS+, p  = 0.013)), and the safety cue, non-reinforced conditioned stimulus (CS-, p  = 0.046)), whereas women living with HIV (WLH) and PTSD demonstrated blunted fear responses compared to women with PTSD only. During extinction, WLH comorbid with PTSD exhibited an increased fear response during the extinction period in comparison to all other groups ( p  = 0.023). Women without PTSD demonstrated a reduction in the fear response during extinction regardless of HIV status., Conclusion: Our findings indicate that HIV further modifies fear psychophysiology in WLH with comorbid PTSD, highlighting the importance of considering HIV status in conjunction with PTSD treatment., Competing Interests: No competing financial interests exist., (© Susie Turkson et al., 2024; Published by Mary Ann Liebert, Inc.)

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, β = .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).

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., Competing Interests: KR has performed scientific consultation for Acer Therapeutics, Bickel, Bionomics, Boehringer Ingelheim, Takeda, and Jazz Pharma; serves on Scientific Advisory Boards for Sage, the Brain Research Foundation, and the National Center for PTSD, he has received sponsored research support from Brains way and Alto Neuroscience. He also receives research funding from the NIH and the Welcome Leap. ED receives or has received research support for work unrelated to this project from NIMH 1R01MH117315-01A1; 5R21MH117512-02, the Department of Veterans Affairs CSP2016; CSP590; MHBA-016-15S; 1I01CX000974-01A1, Auspex Pharmaceuticals, Inc. and Teva Pharmaceuticals, Inc. ED is a full-time attending psychiatrist in the Mental Health Service Line at the Atlanta Veterans Affairs Health Care System, Decatur, GA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GB declared a past co-authorship with author APW., (Copyright © 2024 Lori, Pearce, Katrinli, Carter, Gillespie, Bradley, Wingo, Jovanovic, Michopoulos, Duncan, Hinrichs, Smith and Ressler.)