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.

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.

Research participants” feedback about their participation experiences offers critical insights for improving programs. A shared Empowering the Participant Voice (EPV) infrastructure enabled a multiorganization collaborative to collect, analyze, and act on participants’ feedback using validated participant-centered measures.

A consortium of academic research organizations with Clinical and Translational Science Awards (CTSA) programs administered the Research Participant Perception Survey (RPPS) to active or recent research participants. Local response data also aggregated into a Consortium database, facilitating analysis of feedback overall and for subgroups.

From February 2022 to June 2024, participating organizations sent surveys to 28,096 participants and received 5045 responses (18%). Respondents were 60% female, 80% White, 13% Black, 2% Asian, and 6% Latino/x. Most respondents (85–95%) felt respected and listened to by study staff; 68% gave their overall experience the top rating. Only 60% felt fully prepared by the consent process. Consent, feeling valued, language assistance, age, study demands, and other factors were significantly associated with overall experience ratings. 63% of participants said that receiving a summary of the study results would be very important to joining a future study. Intersite scores differed significantly for some measures; initiatives piloted in response to local findings raised experience scores.

RPPS results from 5045 participants from seven CTSAs provide a valuable evidence base for evaluating participants’ research experiences and using participant feedback to improve research programs. Analyses revealed opportunities for improving research practices. Sites piloting local change initiatives based on RPPS findings demonstrated measurable positive impact.

Latinx populations are underrepresented in clinical research. Asking Latinx research participants about their research experiences, barriers, and facilitators could help to improve research participation for these populations.

The Salud Estres y Resilencia (SER) Hispano cohort study is a longitudinal cohort study of young adult Latinx immigrants whose design and conduct were tailored for their study population. We administered the Research Participant Perception Survey (RPPS) to SER Hispano participants to assess their experiences in the study. We describe overall results from the RPPS and compare results of surveys administered to SER Hispano participants via email versus telephone.

Of 340 participants who were contacted with the RPPS, 142 (42%) responded. Among respondents, 53 (37%) responded by initial email contact; and 89 (63%) responded by subsequent phone contact. The majority of respondents were between 35 and 44 years of age (54%), female (76%), and of Cuban origin (50%). Overall, research participants expressed high satisfaction with their research experience; 84% stated that they would “definitely” recommend research participation to friends and family, with no significant difference by method of survey administration (P = 0.45). The most common factor that was chosen that would influence future research participation was having summary results of the research shared with them (72%).

We found that culturally tailored studies can be good experiences for Latinx research participants; and we found that use of the RPPS can be administered successfully, particularly when administered by more than one method, including telephone, to evaluate and to improve research experiences for this population.

Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).

Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).

Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).

Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Elevated risk of psychosis for ethnic minority groups has generally been shown to be mitigated by high ethnic density. However, past survey studies examining UK Pakistani populations have shown an absence of protective ethnic density effects, which is not observed in other South Asian groups.

To assess the ethnic density effect at a local neighbourhood level, in the UK Pakistani population in East Lancashire.

Data was collected by the East Lancashire Early Intervention Service, identifying all cases of first episode psychosis (FEP) within their catchment area between 2012 and 2020. Multilevel Poisson regression analyses were used to compare incidence rates between Pakistani and White majority groups, while controlling for age, gender and area-level deprivation. The ethnic density effect was also examined by comparing incidence rates across high and low density areas.

A total of 455 cases of FEP (364 White, 91 Pakistani) were identified. The Pakistani group had a higher incidence of FEP compared to the White majority population. A clear effect of ethnic density on rates of FEP was shown, with those in low density areas having higher incidence rates compared to the White majority, whereas incidence rates in high density areas did not significantly differ. Within the Pakistani group, a dose-response effect was also observed, with risk of FEP increasing incrementally as ethnic density decreased.

Higher ethnic density related to lower risk of FEP within the Pakistani population in East Lancashire, highlighting the impact of local social context on psychosis incidence.

Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.

This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.

The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).

Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Patients with Parkinson’s disease (PD) commonly show deficits on tests of visuospatial functioning. The Identi-Fi is a new measure of visual organization and recognition composed of two components. The Visual Recognition (VR) subtest asks persons to identify an object that has been broken its pieces and rearranged, akin to the Hooper Visual Organization Test, but using updated and colorful pictures. The Visual Matching (VM) subtest involves showing the same stimuli, but the examinee must select the correct response from among five choices (1 correct and 4 foils), placing greater demand on visuospatial discrimination. Together, the two subtests comprise the Visual Organization Index (VOI), reflecting overall visual processing and organization ability. The present study examined performance on the Identi-Fi in patients with PD and its association with other aspects of cognition.

Participants were 23 patients with PD (95% male; mean age = 69.7 years [SD = 7.8], range = 47-79) and 12 patients with cognitive concerns (CC) who were intact on neuropsychological testing (excluding consideration of Identi-Fi scores; 50% male, mean age = 71.08 [SD = 6.27], range = 60-78) seen for a neuropsychological evaluation at a large Northeastern medical center. As part of a larger battery, patients completed the Identi-Fi, Trail Making Test (TMT), Category Fluency, Test of Premorbid Functioning (TOPF), and Brief Visuospatial Memory Test, Revised (BVMT-R).

The PD group performed significantly worse than the CC group on VR and VM, as well as VOI, of the Identi-Fi (p < .001). Within the PD group, poorer VR, VM, and VOI performance was associated with lower scores on the TOPF (p < .05), BVMT-R learning (p < .05) and delayed recall (p < .05), as well as TMT Parts A and B (p < .05). VR was significantly correlated with Category Fluency (p < .05), while a trend was seen for the association between VOI and Category Fluency (p = .094).

Identi-Fi performance was worse in the PD group than the CC group, which is consistent with prior research indicating that visuospatial processing is often abnormal in patients with PD. Furthermore, findings indicate that poorer performance on the Identi-Fi in the PD group is associated with poorer cognitive functioning in other domains (i.e., visuospatial learning and memory, processing speed, cognitive flexibility, and semantic fluency), as well as lower premorbid intellectual functioning. While these findings suggest that the Identi-Fi is useful in identifying visuospatial dysfunction in PD, findings should be interpreted with caution given the small sample sizes and uneven gender distribution

Patients with Post-Acute COVID Syndrome (PACS) are reported to commonly experience a variety of cognitive, physical, and neuropsychiatric symptoms well beyond the acute phase of the illness. Notably, concerns involving mood, fatigue, and physical symptoms (e.g., pain, headaches) following COVID-19 appears to be especially prevalent. It is unclear, however, the extent to which such symptoms are associated with cognitive problems in patients with PACS. In the present study, we examined the prevalence of cognitive impairment in a sample of patients with PACS, as well as the relationship between cognitive functioning and several non-cognitive symptoms.

Participants were 38 patients with PACS [71.1% female; mean age = 48.03 years (SD = 11.60) and years of education = 15.26 years (SD = 2.60)] seen for a neuropsychological evaluation at a large Northeastern medical center at least three months from the time of COVID-19 diagnosis (per PCR test). As part of a larger battery, patients completed the Hopkins Verbal Learning Test- Revised (HVLT, learning and delayed recall), Trail Making Test (TMT; time to complete parts A and B), Controlled Oral Word Association Test (COWAT total correct), and Animals (total correct). They also were administered the Chalder Fatigue Scale-11 (CFS-11), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Patient Health Questionnaire (PHQ-15). The percentage of patients with scores in the impaired range (z < -1.5) on cognitive tests was determined. Correlations between cognitive and non-cognitive measures were also examined.

The most frequent impairment was seen for COWAT (21.2%), followed by TMT-A and TMT-B (both 13.9%), then category fluency (9.1%). No patients were impaired on HVLT-R Learning and only one (4%) for HVLT-R Delayed Recall. Overall, the sample endorsed considerable depression, anxiety, fatigue, as well as physical symptoms. Greater fatigue was associated with worse verbal learning, processing speed, cognitive flexibility, and verbal fluency (letter and category). Worse physical symptom severity was related to poorer verbal delayed recall and cognitive flexibility. Greater anxiety was also associated with worse cognitive flexibility, while more severe depression was related to poorer category fluency.

In our sample of patients with PACS, seen for evaluation several months since contracting COVID-19, phonemic fluency was the most common cognitive impairment, though less than a quarter were impaired on any given cognitive test. Importantly, several associations were observed between cognitive test performance and non-cognitive symptoms commonly endorsed by patients with PACS. These findings highlight the importance of assessing multiple factors potentially contributing to cognitive impairment in these patients. Interventions designed to address such symptoms may be helpful in ameliorating cognitive functioning in those with PACS.

Mild cognitive impairment (MCI) is characterized by subjective and objective memory concerns, though additional cognitive concerns are commonly reported, including changes in executive functions (EF). Rabin et al. (2006) showed that a sample of research participants with MCI endorsed problems with their EFs, especially working memory. Similarly, those with subjective cognitive dysfunction (SCD) also reported greater difficulty with aspects of their EF than a healthy comparison sample of older adults (HC). In the present study, we investigated subjective EF in clinical samples of older adults with MCI or SCD, which represents a more naturalistic sample relative to a research sample. Furthermore, we evaluated whether subjective EF varied in these groups depending on whether patients were "young-old" versus "old-old" given prior research indicating objective cognitive differences between these age groups.

Participants were 135 older adults (53 MCI, 52 SCD, and 30 HC) matched for age (p = .116) and education (p = .863). Dichotomous categorization of age used the sample median (72 years) as cutoff score with 72 participants in the young-old group (mean age = 65.8 ± 4.7 years) and 63 in the old-old group (mean age = 78.1 ± 3.7 years). Participants completed the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), assessing executive functions in everyday life over the past month. The BRIEF-A yields an overall score (Global Executive Composite [GEC]) composed of two index scores (Behavioral Regulation Index [BRI] and Metacognition Index [MI]) and nine clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). A diagnosis by age-group multivariate analysis of variance (MANOVA) with post-hoc comparisons for diagnosis using a Tukey HSD correction was conducted using SPSS Version 24.

MCI and SCD groups endorsed worse EF on all three index scores (ps < .005) and all nine clinical scales (ps < .05) relative to the HC group, and the MCI group reported worse initiation relative to the SCD group. Additionally, worse executive functions on all three index scores (ps < .05) and four clinical scales (ps < .05; emotional control, self-monitoring, planning/organization, and task monitoring) were reported by the young-old group relative to the old-old group. No diagnosis by age-group interactions were observed.

Problems with aspects of EF were endorsed by older adults with MCI and SCD compared to HCs across all indices and clinical scales; however, only initiation was reported to be worse in MCI than those with SCD. Additionally, the young-old group endorsed having worse EF than the old-old group across BRIEF-A indices and several more specific aspects of EF, without a moderating effect of diagnosis. These findings highlight the importance of assessing subjective EF in older adults, as they may be early indicators of cognitive change, prior to objective evidence of cognitive decline. Furthermore, results also point to differences in how the young-old and old-old perceive their EF in everyday life.