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.

Mental health problems commonly persist from childhood to adulthood. This study tested whether young adult life transitions can improve adult mental health symptoms after adjusting for childhood mental health symptoms.

The analysis uses data from the prospective, representative Great Smoky Mountains Study. Life transitions (e.g., high school completion, partnering, parenthood, and living independently) were assessed up to three times in young adulthood (ages 18 to 26; 3,241 observations). A cumulative variable counted the number of young adult transitions. Emotional, substance use, and antisocial personality symptoms were assessed at age 30 (1,154 participants or 81.2% of the original sample). Propensity models adjusted for early life adversities and psychiatric symptoms.

Multiple young adult transitions were common (m = 4.62; SD = 1.57). After adjusting for childhood mental health problems and adversities, each additional transition was significantly associated with a reduction in subsequent adult emotional symptoms (β = −0.34, 95% CI: −0.59, −0.08, p = 0.01) and adult antisocial personality disorder symptoms (β = −0.08, 95% CI: −0.14, −0.02, p < 0.001. These associations were stronger in males than in females. Young adult transitions were not associated with reductions in subsequent substance use symptoms (β = −0.04; 95% CI: −0.11, 0.03, p = 0.30). Young adult transitions related to educational milestones and consistent employment were associated with the largest reductions in symptoms.

In this cohort study, life transitions during young adulthood were associated with reduced emotional and behavioral symptoms in adulthood. These transitions may constitute a potential mental health turning point and a specific, modifiable target for social policies.

Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

We conducted a quantitative analysis of the microbial burden and prevalence of epidemiologically important pathogens (EIP) found on long-term care facilities (LTCF) environmental surfaces.

Microbiological samples were collected using Rodac plates (25cm2/plate) from resident rooms and common areas in five LTCFs. EIP were defined as MRSA, VRE, C. difficile and multidrug-resistant (MDR) Gram-negative rods (GNRs).

Rooms of residents with reported colonization had much greater EIP counts per Rodac (8.32 CFU, 95% CI 8.05, 8.60) than rooms of non-colonized residents (0.78 CFU, 95% CI 0.70, 0.86). Sixty-five percent of the resident rooms and 50% of the common areas were positive for at least one EIP. If a resident was labeled by the facility as colonized with an EIP, we only found that EIP in 30% of the rooms. MRSA was the most common EIP recovered, followed by C. difficile and MDR-GNR.

We found frequent environmental contamination with EIP in LTCFs. Colonization status of a resident was a strong predictor of higher levels of EIP being recovered from his/her room.

Cross-sectional studies have identified health risks associated with epigenetic aging. However, it is unclear whether these risks make epigenetic clocks ‘tick faster’ (i.e. accelerate biological aging). The current study examines concurrent and lagged within-person changes of a variety of health risks associated with epigenetic aging.

Individuals from the Great Smoky Mountains Study were followed from age 9 to 35 years. DNA methylation profiles were assessed from blood, at multiple timepoints (i.e. waves) for each individual. Health risks were psychiatric, lifestyle, and adversity factors. Concurrent (N = 539 individuals; 1029 assessments) and lagged (N = 380 individuals; 760 assessments) analyses were used to determine the link between health risks and epigenetic aging.

Concurrent models showed that BMI (r = 0.15, PFDR < 0.01) was significantly correlated to epigenetic aging at the subject-level but not wave-level. Lagged models demonstrated that depressive symptoms (b = 1.67 months per symptom, PFDR = 0.02) in adolescence accelerated epigenetic aging in adulthood, also when models were fully adjusted for BMI, smoking, and cannabis and alcohol use.

Within-persons, changes in health risks were unaccompanied by concurrent changes in epigenetic aging, suggesting that it is unlikely for risks to immediately ‘accelerate’ epigenetic aging. However, time lagged analyses indicated that depressive symptoms in childhood/adolescence predicted epigenetic aging in adulthood. Together, findings suggest that age-related biological embedding of depressive symptoms is not instant but provides prognostic opportunities. Repeated measurements and longer follow-up times are needed to examine stable and dynamic contributions of childhood experiences to epigenetic aging across the lifespan.

Many preoperative urine cultures are of low value and may even lead to patient harms. This study sought to understand practices around ordering preoperative urine cultures and prescribing antibiotic treatment.

Open-ended, semi-structured qualitative interviews

5 Veterans Affairs hospitals.

Interviews with 14 surgeons (9 surgeons, 5 surgical leaders), 7 infectious disease physicians, 8 surgical advanced practice providers (APPs), 1 surgical nurse manager, 3 infectious disease pharmacists, 1 hospitalist, and 1 lab manager.

We interviewed participants using a qualitative semi-structured interview guide. Collected data was coded inductively and with the Dual Process Model (DPM) using MAXQDA software. Data in the “Testing Decision-Making” code was further reviewed using the concept of perceived risk as a sensitizing concept.

We identified themes relating to surgeons’ concerns about de-implementing preoperative urine cultures to detect asymptomatic bacteriuria (ASB) in patients undergoing non-urological procedures: (1) anxiety and uncertainty surrounding missing infection signs spanned surgical specialties, (2) there were perceived risks of negative consequences associated with omitting urine cultures and treatment prior to specific procedure sites and types, and additionally, (3) participants suggested potential routes for adjusting these perceived risks to facilitate de-implementation acceptance. Notably, participants suggested that leadership support and peer engagement could help improve surgeon buy-in.

Concerns about perceived risks sometimes outweigh the evidence against routine preoperative urine cultures to detect ASB. Evidence from trusted peers may improve openness to de-implementing preoperative urine cultures.

Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study’s aim was to assess the current status of states’ OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States.

Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).

The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher’s exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols.

Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%).

There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.

Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

Mild traumatic brain injury (mTBI), depression, and posttraumatic stress disorder (PTSD) are a notable triad in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) Veterans. With the comorbidity of depression and PTSD in Veterans with mTBI histories, and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in areas such as prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. Identifying predictors of psychiatric symptom change following CCT would further inform the interventional approach. We sought to examine neuropsychological predictors of PTSD and depressive symptom improvement in Veterans with a history of mTBI who received CCT.

37 OEF/OIF/OND Veterans with mTBI history and cognitive complaints received 10-weekly 120-minute CCT group sessions as part of a clinical trial. Participants completed a baseline neuropsychological assessment including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD Checklist-Military Version; Beck Depression Inventory-II) at baseline, post-treatment, and 5-week follow-up. Paired samples t-tests were used to examine statistically significant change in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores (p^.05) were entered as independent variables in separate multiple linear regression analyses to predict symptom change at post-treatment and follow-up.

Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (>17.5% score reduction) and over 20% had clinically meaningful improvement in PTSD symptoms (>10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores (re-experiencing, avoidance/numbing, and arousal) revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on D-KEFS Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both D-KEFS Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on D-KEFS Trail Making Test Switching was associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed worse processing speed and worse aspects of executive functioning at baseline significantly predicted depressive symptom improvement at post-treatment and follow-up.

Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve. Although CCT is not a primary treatment for PTSD or depressive symptoms, our results support consideration of including CCT in hybrid treatment approaches. Further research should examine these relationships in larger samples.

Cognitive dysfunction is prominent in homeless and precariously housed persons, and memory dysfunction is the most pervasive domain. The presence of multimorbid physical and mental illness suggests that several underlying mechanisms of memory impairment may be at play. The serial position phenomenon describes the tendency to best recall the beginning (primacy effect) and last (recency effect) words on a supra-span wordlist. Recency recall engages executive and working-memory systems, whereas primacy recall depends on long-term memory. This study investigates memory dysfunction in a homeless and precariously housed sample by identifying and characterizing unique subtypes of serial position profiles on a test of verbal memory.

Data were used from a 20-year study of homeless and precariously housed adults recruited from an impoverished neighbourhood in Vancouver, Canada. Participants were sub-grouped according to their serial position profile on the Hopkins Verbal Learning Test-Revised using a latent profile analysis (LPA; n = 411). Paired samples t-tests were conducted to determine differences in percent recall from each word-list region within classes. Linear regression analyses were used to examine between-class differences in mean serial position scores and other cognitive measures (memory, attention, processing speed, cognitive control). Covariates included age, sex, and education.

LPA identified two profiles characterized by (1) reduced primacy relative to recency (RP; n = 150); and (2) reduced recency relative to primacy (RR; n = 261). Pairwise comparisons within the RP class showed that recency was better than primacy (p < .001, d = .66) and middle recall (p < .001, d = .52), with no difference between primacy and middle recall (p = .68, d = .04). All pairwise comparisons differed within the RR class (primacy > middle recall: p < .001, d = 1.85; primacy > recency recall: p < .001, d = 1.32; middle > recency recall: p < .05, d = .132). The RP class had worse performance on measures of total immediate (ß = .47, p < .001) and delayed verbal recall (ß = .32, p < .001); processing speed (ß = .20, p < .001); and cognitive control (ß = .22, p < .001). The RR class made more repetition errors (ß = .25, p < .001).

These findings support substantial heterogeneity in memory functioning in homeless and precariously housed individuals. The RP profile was characterized by poorer cognitive functioning across several domains, which suggests multiple contributions to memory impairment, including dysfunction of long-term memory circuitry. The RR profile with their higher number of repetition errors, may experience difficulties with self-monitoring in verbal learning. Subsequent studies will explore the neurobiological underpinnings of these subgroups to further characterize profiles and identify targets for cognitive intervention.

Precariously housed individuals are exposed to multiple adverse factors negatively impacting neurocognitive functioning. Additionally, this population is subjected to poor life outcomes, such as impaired psychosocial functioning. Neurocognitive functioning plays an important role in psychosocial functioning and may be especially critical for precariously housed individuals who face numerous barriers in their daily lives. However, few studies have explicitly examined the cognitive determinants of functional outcomes in this population. Cognitive intraindividual variability (IIV) involves the study of within-person differences in neurocognitive functioning and has been used as marker of frontal system pathology. Increased IIV has been associated with worse cognitive performance, cognitive decline, and poorer everyday functioning. Hence, IIV may add to the predictive utility of commonly used neuropsychological measures and may serve as an emergent predictor of poor outcomes in at-risk populations. The objective of the current study was to examine IIV as a unique index of the neurocognitive contributions to functional outcomes within a large sample of precariously housed individuals. It was hypothesized that greater IIV would be associated with poorer current (i.e., baseline) and long-term (i.e., up to 12 years) psychosocial functioning.

Four hundred and thirty-seven adults were recruited from single-room occupancy hotels located in the Downtown Eastside of Vancouver, Canada (Mage = 44 years, 78% male) between November 2008 and November 2021. Baseline neurocognitive functioning was assessed at study enrolment. Scores from the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale (RFS), the physical component score (PCS) and the mental component score (MCS) of the 36-Item Short Form Survey Instrument were obtained at participants’ baseline assessments and at their last available follow-up assessment to represent baseline and long-term psychosocial functioning, respectively. Using an established formula, an index of IIV was derived using a battery of standardized tests that broadly assessed verbal learning and memory, sustained attention, mental flexibility, and cognitive control. A series of multiple linear regressions were conducted to predict baseline and long-term social and role functioning (average across SOFAS and RFS scores), and PCS and MCS scores from IIV. In each of the models, we also included common predictors of functioning, including a global cognitive composite score, age, and years of education.

The IIV index and the global composite score did not explain a significant proportion of the variance in baseline and long-term social and role functioning (p > .05). However, IIV was a significant predictor of baseline (B = -3.84, p = .021) and long-term (B = -3.58, p = .037) PCS scores, but not MCS scores (p > .05). The global composite score did not predict baseline or long-term PCS scores.

IIV significantly predicted baseline and long-term physical functioning, but not mental functioning or social and role functioning, suggesting that IIV may be a sensitive marker for limitations in everyday functioning due to physical health problems in precariously housed individuals. Critically, the present study is the first to show that IIV may be a useful index for predicting poor long-term health-related outcomes in this population compared to traditional neuropsychological measures.