Prolonged grief disorder (PGD) is a chronic, impairing state of intense grief that is responsive to specialised intervention. Online journalling has the potential to reduce PGD symptoms.

To assess whether reminiscence via online journalling facilitates bereavement adjustment – specifically, to identify key themes in online grief journals and examine associations between types of reminiscence and changes in PGD symptom severity.

A cohort of 96 bereaved adults completed 7 days of online journalling on the Living Memory Home (LMH) bereavement website. Participants were recruited from clinics, bereavement support groups and a National Institutes of Health-funded, web-based platform. The Prolonged Grief Disorder-Revised scale (PG-13-R) was administered at baseline and at 1-week and 1-month follow-up.

Descriptive analysis revealed a reduction in PG-13-R scores from baseline to 1-week follow-up (mean difference −3.7, 95% CI: −4.9, −2.5, P < 0.001) and 1-month follow-up (mean difference −5.0, 95% CI: −6.4, −3.7. P < 0.001). Mixed-methods analysis revealed significant negative associations between reflection on negative traits of the deceased and PG-13-R score at all three time points, and between reflection on past experiences with the deceased and PG-13-R score at baseline. Expression of regret and guilt was significantly associated with reduction in PG-13-R scores from 1-week to 1-month follow-up.

Engagement in the LMH website demonstrated significant declines in PGD symptom severity after 1 week of online journalling and at 1-month follow-up. Guided reflection on memories of the deceased, and even on negative or emotionally challenging memories, shows potential for reducing symptoms of PGD.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

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.

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.

Decentralized research has many advantages; however, little is known about the representativeness of a source population in decentralized studies. We recruited participants aged 18-64 years from four states from June to December 2022 for a prospective cohort study to assess viral epidemiology. Our aim was to determine the association between age, gender, race/ethnicity, rurality, and socioeconomic status (SES) on study participation in a decentralized prospective cohort study.

We consented 9,286 participants from 231,099 (4.0%) adults with the mean age of 45.6 years (±12.0). We used an electronic decentralized approach for recruitment. Consented participants were more likely to be non-Hispanic White, female, older, urban residents, have more health conditions, and possessed higher socioeconomic status (SES) compared to those non-consented.

We observed an interaction between SES and race-ethnicity on the odds of consent (P = 0.006). Specifically, SES did not affect non-Hispanic white participation rates(OR 1.24 95% CI 1.16 – 1.32] for the highest SES quartile compared to those with the lowest SES quartile) as much as it did participants combined across the other races (OR 1.73; 95% CI 1.45 – 2.98])

The relationship between SES and consent rates might be disproportionately greater in historically disadvantaged groups, compared to non-Hispanic White. It suggests that instead of focusing on enrollment of specific minority groups in research, there is value in future research exploring and addressing the diversity of barriers to trials within minority groups. Our study highlights that decentralized studies need to address social determinants of health, especially in under-resourced populations.

Hallucinations are common and distressing symptoms in Parkinson’s disease (PD). Treatment response in clinical trials is measured using validated questionnaires, including the Scale for Assessment of Positive Symptoms-Hallucinations (SAPS-H) and University of Miami PD Hallucinations Questionnaire (UM-PDHQ). The minimum clinically important difference (MCID) has not been determined for either scale. This study aimed to estimate a range of MCIDs for SAPS-H and UM-PDHQ using both consensus-based and statistical approaches.

A Delphi survey was used to seek opinions of researchers, clinicians, and people with lived experience. We defined consensus as agreement ≥75%. Statistical approaches used blinded data from the first 100 PD participants in the Trial for Ondansetron as Parkinson’s Hallucinations Treatment (TOP HAT, NCT04167813). The distribution-based approach defined the MCID as 0.5 of the standard deviation of change in scores from baseline at 12 weeks. The anchor-based approach defined the MCID as the average change in scores corresponding to a 1-point improvement in clinical global impression-severity scale (CGI-S).

Fifty-one researchers and clinicians contributed to three rounds of the Delphi survey and reached consensus that the MCID was 2 points on both scales. Sixteen experts with lived experience reached the same consensus. Distribution-defined MCIDs were 2.6 points for SAPS-H and 1.3 points for UM-PDHQ, whereas anchor-based MCIDs were 2.1 and 1.3 points, respectively.

We used triangulation from multiple methodologies to derive the range of MCID estimates for the two rating scales, which was between 2 and 2.7 points for SAPS-H and 1.3 and 2 points for UM-PDHQ.

Passive leg raising is used to predict who will benefit from fluid therapy in critically ill patients, including children. Patients with a Fontan circulation may have a different haemodynamic response to a fluid challenge by passive leg raising.

The haemodynamic response of 31 paediatric patients with a Fontan circulation from the outpatient clinic (median age 14.0 years) and 35 healthy controls (median age 12.8 years) to passive leg raising was evaluated non-invasively by echocardiography for the assessment of, e.g., velocity time integral across the (neo)aortic valve, blood pressure measurements, and respiration. Participants were considered responders when the velocity time integral increased ≥ 10.0%.

Overall, patients and controls did not differ in the haemodynamic response. Twelve patients (38.7%) and 8 controls (22.9%) were responders, which was not statistically different (P = 0.22). Responders in the patient and control group also had a similar echo-estimated velocity time integral increase of + 18.9% and + 15.2%, respectively (P = 0.91). There was no difference in echo-estimated velocity time integral change between patient and control non-responders with a decrease of −1.4% and −6.4%, respectively (P = 0.70) and no difference in the amount of patients who were negatively affected by passive leg raising, ith a decrease of ≤−10.0% in 7 patients (22.6%) and 9 controls (25.7%)(P = 0.77).

The haemodynamic response of ambulatory paediatric patients with a Fontan circulation to passive leg raising is like that of healthy controls. Patients who did not respond were similarly affected as healthy controls. Whether the haemodynamic response is different in critically ill patients warrants further investigation.

The Netherlands National Trial Register (NTR), Trial: NL6415; date of registration 20-07-2017; Trial information: https://www.trialregister.nl/trial/6415.

Childhood adversity has been associated with increased peripheral inflammation in adulthood. However, not all individuals who experience early adversity develop these inflammatory outcomes. Separately, there is also a link between various internalizing emotional distress conditions (e.g. depression, anxiety, and fear) and inflammation in adulthood. It is possible the combination of adult emotional distress and past childhood adversity may be uniquely important for explaining psychopathology-related immune dysfunction at midlife.

Using data from the Midlife in the United States (MIDUS) study (n = 1255), we examined whether internalizing, defined as past 12-month emotional distress symptomatology and trait neuroticism, moderated associations between childhood adversity and heightened inflammation in adulthood. Using latent variable modeling, we examined whether transdiagnostic or disorder-specific features of emotional distress better predicted inflammation.

We observed that childhood adversity only predicted adult inflammation when participants also reported adult internalizing emotional distress. Furthermore, this moderation effect was specific to the transdiagnostic factor of emotional distress rather than the disorder-specific features.

We discuss the possibility that adult internalizing symptoms and trait neuroticism together may signal the presence of temporally stable vulnerabilities that amplify the impact of childhood adversity on midlife immune alterations. The study highlights the importance of identifying emotional distress in individuals who have experienced childhood adversity to address long-term immune outcomes and enhance overall health.