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.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Patients with Opioid Use Disorder (OUD) are prone to Multidrug-Resistant Organism (MDRO) colonization and infections, thus at risk for worse outcomes during critical illness. Understanding the prevalence and predictors of MDRO infections is essential to optimize interventions and treatments.

Retrospective cohort study.

The study evaluated the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) between January 1, 2018, and July 31, 2023. It included adults admitted to an ICU with bacterial infections and positive cultures obtained within 48 hours of admission. Demographics, clinical traits, and MDRO isolation rates were analyzed using descriptive statistics, univariate methods, and Least Absolute Shrinkage and Selection Operator (LASSO) regression.

MDRO isolation occurred in 178 of 790 patients (22.5%), with methicillin-resistant Staphylococcus aureus as the most frequently isolated organism. LASSO regression identified housing insecurity (OR: 1.79, 95% CI 1.09–2.93, P = .022), no receipt of medications for OUD treatment (OR: 1.56, 95% CI 1.06–2.29, P = .023), positive hepatitis C virus (HCV) status (OR: 2.19, 95% CI 1.19–4.03, P = .012), and intravenous antibiotic use in the prior 90 days (OR: 1.04 per 24 h, 95% CI 1.01–1.07, P = .007) as significant predictors of MDRO isolation.

The study highlights a high prevalence of MDRO isolation in critically ill OUD patients admitted for infection-related issues with positive cultures obtained within 48 hours of admission, influenced by factors like housing insecurity, no receipt of medications for OUD treatment, HCV status, and prior antibiotic use.

To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP).

Retrospective, exact matched, multicenter cohort study from October 1, 2018 – March 31, 2023.

All hospitals across the Mayo Clinic Enterprise.

Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of “respiratory tract infection” within 48 hours of hospitalization.

PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS).

15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134).

PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.

Fear learning is a core component of conceptual models of how adverse experiences may influence psychopathology. Specifically, existing theories posit that childhood experiences involving childhood trauma are associated with altered fear learning processes, while experiences involving deprivation are not. Several studies have found altered fear acquisition in youth exposed to trauma, but not deprivation, although the specific patterns have varied across studies. The present study utilizes a longitudinal sample of children with variability in adversity experiences to examine associations among childhood trauma, fear learning, and psychopathology in youth.

The sample includes 170 youths aged 10–13 years (M = 11.56, s.d. = 0.47, 48.24% female). Children completed a fear conditioning task while skin conductance responses (SCR) were obtained, which included both acquisition and extinction. Childhood trauma and deprivation severity were measured using both parent and youth report. Symptoms of anxiety, externalizing problems, and post-traumatic stress disorder (PTSD) were assessed at baseline and again two-years later.

Greater trauma-related experiences were associated with greater SCR to the threat cue (CS+) relative to the safety cue (CS−) in early fear acquisition, controlling for deprivation, age, and sex. Deprivation was unrelated to fear learning. Greater SCR to the threat cue during early acquisition was associated with increased PTSD symptoms over time controlling for baseline symptoms and mediated the relationship between trauma and prospective changes in PTSD symptoms.

Childhood trauma is associated with altered fear learning in youth, which may be one mechanism linking exposure to violence with the emergence of PTSD symptoms in adolescence.

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.

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.

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.

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.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Cognitive therapy and behavioural activation are both widely applied and effective psychotherapies for depression, but it is unclear which works best for whom. Individual participant data (IPD) meta-analysis allows for examining moderators at the participant level and can provide more precise effect estimates than conventional meta-analysis, which is based on study-level data.

This article describes the protocol for a systematic review and IPD meta-analysis that aims to compare the efficacy of cognitive therapy and behavioural activation for adults with depression, and to explore moderators of treatment effect. (PROSPERO: CRD42022341602)

Systematic literature searches will be conducted in PubMed, PsycINFO, EMBASE and the Cochrane Library, to identify randomised clinical trials comparing cognitive therapy and behavioural activation for adult acute-phase depression. Investigators of these trials will be invited to share their participant-level data. One-stage IPD meta-analyses will be conducted with mixed-effects models to assess treatment effects and to examine various available demographic, clinical and psychological participant characteristics as potential moderators. The primary outcome measure will be depressive symptom level at treatment completion. Secondary outcomes will include post-treatment anxiety, interpersonal functioning and quality of life, as well as follow-up outcomes.

To the best of our knowledge, this will be the first IPD meta-analysis concerning cognitive therapy versus behavioural activation for adult depression. This study has the potential to enhance our knowledge of depression treatment by using state-of-the-art statistical techniques to compare the efficacy of two widely used psychotherapies, and by shedding more light on which of these treatments might work best for whom.

Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.

We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).

We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.

This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.

We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.

Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.

These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.

Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.

Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.

In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.