Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.

The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.

ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.

This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.

The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.

To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.

We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.

Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.

Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

We live in a time of significant global risk. Some research has focused on understanding systemic sources of this risk, while other research has focused on possible worst-case outcomes. In this article, we bring together these two areas of research and provide a simple conceptual framework that shows how emergent features of the global system contribute to the risk of global catastrophe.

Humanity faces a complex and dangerous global risk landscape, and many different terms and concepts have been used to make sense of it. One broad strand of research characterises how risk emerges within the complex global system, using concepts like systemic risk, Anthropocene risk, synchronous failure, negative social tipping points, and polycrisis. Another focuses on possible worst-case outcomes, using concepts like global catastrophic risk (GCR), existential risk, and extinction risk. Despite their clear relevance to each other, connections between these two strands remain limited. Here, we provide a simple conceptual framework that synthesises these research strands and shows how emergent properties of the global system contribute to the risk of global catastrophic outcomes. In particular, we show that much of GCR stems from the interaction of hazards and vulnerabilities that arise endogenously within the global system, and how ‘systems thinking’ and complex adaptive systems theory can help illuminate this. We also highlight some unique challenges that systemic sources of GCR pose for risk assessment and mitigation, discuss insights for policy, and outline potential paths forward.

The global system is generating global catastrophic risk.

To compare clinical failure of intravenous vs intravenous with oral step-down antibiotic treatment for Streptococcus and Enterococcus bloodstream infection.

Multicenter, retrospective, cohort study at one academic medical center and eight community hospitals.

Hospitalized adult patients with blood cultures positive for Streptococcus or Enterococcus were included. Patients were excluded if they had complicated infection, had polymicrobial bacteremia, received less than 5 days of therapy, or died before completing therapy.

Patients who completed intravenous therapy were compared with patients who transitioned to oral therapy after 3 to 7 days. The primary endpoint was clinical failure, defined as 90-day all-cause mortality or recurrent bacteremia. The primary analysis excluded patients with unknown outcomes, and the sensitivity analysis treated them as failures.

429 patients were included (intravenous group: n = 225; oral step-down group; n = 204). The intravenous group had more comorbidities and vasopressor use. The intravenous group had a higher risk of clinical failure in the primary analysis (17.5% vs. 8.8%; adjusted OR 2.14 [95% CI, 1.09–4.2]; p = 0.03) while the sensitivity analysis found no difference in clinical failure (adjusted OR 1.1 [95% CI, 0.69–1.74], p = 0.69). The oral step-down group had a mean length of stay of 9.2 days shorter than the intravenous group ([95% CI, 7.5–11.0]; p<0.001).

Oral step-down therapy was not associated with an increased risk of clinical failure compared to a full course of intravenous therapy for uncomplicated Streptococcus and Enterococcus bloodstream infections. Patients with more comorbidities or who required vasopressors were less likely to be switched to oral therapy.

Recent theories have implicated inflammatory biology in the development of psychopathology and maladaptive behaviors in adolescence, including suicidal thoughts and behaviors (STB). Examining specific biological markers related to inflammation is thus warranted to better understand risk for STB in adolescents, for whom suicide is a leading cause of death.

Participants were 211 adolescent females (ages 9–14 years; Mage = 11.8 years, SD = 1.8 years) at increased risk for STB. This study examined the prospective association between basal levels of inflammatory gene expression (average of 15 proinflammatory mRNA transcripts) and subsequent risk for suicidal ideation and suicidal behavior over a 12-month follow-up period.

Controlling for past levels of STB, greater proinflammatory gene expression was associated with prospective risk for STB in these youth. Similar effects were observed for CD14 mRNA level, a marker of monocyte abundance within the blood sample. Sensitivity analyses controlling for other relevant covariates, including history of trauma, depressive symptoms, and STB prior to data collection, yielded similar patterns of results.

Upregulated inflammatory signaling in the immune system is prospectively associated with STB among at-risk adolescent females, even after controlling for history of trauma, depressive symptoms, and STB prior to data collection. Additional research is needed to identify the sources of inflammatory up-regulation in adolescents (e.g., stress psychobiology, physiological development, microbial exposures) and strategies for mitigating such effects to reduce STB.