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.

DSM-5 specifies bulimia nervosa (BN) severity based on specific thresholds of compensatory behavior frequency. There is limited empirical support for such severity groupings. Limited support could be because the DSM-5’s compensatory behavior frequency cutpoints are inaccurate or because compensatory behavior frequency does not capture true underlying differences in severity. In support of the latter possibility, some work has suggested shape/weight overvaluation or use of single versus multiple purging methods may be better severity indicators. We used structural equation modeling (SEM) Trees to empirically determine the ideal variables and cutpoints for differentiating BN severity, and compared the SEM Tree groupings to alternate severity classifiers: the DSM-5 indicators, single versus multiple purging methods, and a binary indicator of shape/weight overvaluation.

Treatment-seeking adolescents and adults with BN (N = 1017) completed self-report measures assessing BN and comorbid symptoms. SEM Trees specified an outcome model of BN severity and recursively partitioned this model into subgroups based on shape/weight overvaluation and compensatory behaviors. We then compared groups on clinical characteristics (eating disorder symptoms, depression, anxiety, and binge eating frequency).

SEM Tree analyses resulted in five severity subgroups, all based on shape/weight overvaluation: overvaluation <1.25; overvaluation 1.25–3.74; overvaluation 3.75–4.74; overvaluation 4.75–5.74; and overvaluation ≥5.75. SEM Tree groups explained 1.63–6.41 times the variance explained by other severity schemes.

Shape/weight overvaluation outperformed the DSM-5 severity scheme and single versus multiple purging methods, suggesting the DSM-5 severity scheme should be reevaluated. Future research should examine the predictive utility of this severity scheme.

Inadequate recruitment and retention impede clinical trial goals. Emerging decentralized clinical trials (DCTs) leveraging digital health technologies (DHTs) for remote recruitment and data collection aim to address barriers to participation in traditional trials. The ACTIV-6 trial is a DCT using DHTs, but participants’ experiences of such trials remain largely unknown. This study explored participants’ perspectives of the ACTIV-6 DCT that tested outpatient COVID-19 therapeutics.

Participants in the ACTIV-6 study were recruited via email to share their day-to-day trial experiences during 1-hour virtual focus groups. Two human factors researchers guided group discussions through a semi-structured script that probed expectations and perceptions of study activities. Qualitative data analysis was conducted using a grounded theory approach with open coding to identify key themes.

Twenty-eight ACTIV-6 study participants aged 30+ years completed a virtual focus group including 1–4 participants each. Analysis yielded three major themes: perceptions of the DCT experience, study activity engagement, and trust. Participants perceived the use of remote DCT procedures supported by DHTs as an acceptable and efficient method of organizing and tracking study activities, communicating with study personnel, and managing study medications at home. Use of social media was effective in supporting geographically dispersed participant recruitment but also raised issues with trust and study legitimacy.

While participants in this qualitative study viewed the DCT-with-DHT approach as reasonably efficient and engaging, they also identified challenges to address. Understanding facilitators and barriers to DCT participation and DHT interaction can help improve future research design.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake.

Pooled pregnancy cohort studies.

Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020.

A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use.

Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1–2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35–40 v. <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v. healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v. never).

One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n-3 supplement use was uncommon, even among those who did not consume fish.

As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).

The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.

The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.

Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.

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.