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.

The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.

Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.

Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).

Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.

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.

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.

Radiotherapy for pediatric brain tumor has been associated with late cognitive effects. Compared to conventional photon radiotherapy (XRT), proton radiotherapy (PRT) delivers less radiation to healthy brain tissue. PRT has been associated with improved long term cognitive outcomes compared to XRT. However, there is limited research comparing the effects of XRT and PRT on verbal memory outcomes.

Survivors of pediatric brain tumor treated with either XRT (n = 29) or PRT (n = 51) completed neuropsychological testing > 1 year following radiotherapy. XRT and PRT groups were similar with respect to sex, handedness, race, age at diagnosis, age at evaluation, tumor characteristics, and treatment history (i.e., craniospinal irradiation, craniotomy, shunting, chemotherapy, radiation dose). Verbal learning and memory were assessed using the age-appropriate version of the California Verbal Learning Test (CVLT-II/CVLT-C). Measures of intellectual functioning, executive functioning, attention and adaptive behavior were also collected. Performance on neuropsychological measures was compared between treatment groups (XRT vs. PRT) using analysis of covariance (ANCOVA). On the CVLT, each participant was classified as having an encoding deficit profile (i.e., impaired learning, recall, and recognition), retrieval deficit profile (i.e., impaired recall but intact recognition), intact profile, or other profile. Chi-squared tests of independence were used to compare the probability of each memory profile between treatment groups. Pearson correlation was used to examine associations between memory performance and strategy use, intellectual functioning, adaptive behavior, attention, and executive functioning.

Overall, patients receiving PRT demonstrated superior verbal learning (CVLT Trials 1-5; t(76) = 2.61, p = .011), recall (CVLT Long Delay Free; t(76) = 3.57, p = .001) and strategy use (CVLT Semantic Clustering; t(76) = 2.29, p = .025) compared to those treated with XRT. Intact performance was more likely in the PRT group than the XRT group (71% PRT, 38% XRT; X2 = 8.14, p = .004). Encoding and retrieval deficits were both more common in the XRT group, with encoding problems being most prevalent (Encoding Deficits: 31% XRT, 12% PRT, X2 = 4.51, p = .034; Retrieval Deficits: 17% XRT, 4% PRT, X2 = 4.11, p = .043). Across all participants, semantic clustering predicted better encoding (r = .28, p = .011) and retrieval (r = .26, p = .022). Better encoding predicted higher intellectual (r = .56, p < .001) and adaptive functioning (r = .30, p = .011), and fewer parent-reported concerns about day-today attention (r = -.36, p = .002), and cognitive regulation (r = -.35, p = .002).

Results suggest that PRT is associated with superior verbal memory outcomes compared to XRT, which may be driven by encoding skills and use of learning strategies. Moreover, encoding ability predicted general intellectual ability and day-to-day functioning. Future work may help to clarify underlying neural mechanisms associated with verbal memory decline following radiotherapy, which will better inform treatment approaches for survivors of pediatric brain tumor.

Repetitive transcranial magnetic stimulation (TMS) is an evidenced based treatment for adults with treatment resistant depression (TRD). The standard clinical protocol for TMS is to stimulate the left dorsolateral prefrontal cortex (DLPFC). Although the DLPFC is a defining region in the cognitive control network of the brain and implicated in executive functions such as attention and working memory, we lack knowledge about whether TMS improves cognitive function independent of depression symptoms. This exploratory analysis sought to address this gap in knowledge by assessing changes in attention before and after completion of a standard treatment with TMS in Veterans with TRD.

Participants consisted of 7 Veterans (14.3% female; age M = 46.14, SD = 7.15; years education M = 16.86, SD = 3.02) who completed a full 30-session course of TMS treatment and had significant depressive symptoms at baseline (Patient Health Questionnaire-9; PHQ-9 score >5). Participants were given neurocognitive assessments measuring aspects of attention [Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) subtests: Digits Forward, Digits Backward, and Number Sequencing) at baseline and again after completion of TMS treatment. The relationship between pre and post scores were examined using paired-samples t-test for continuous variables and a linear regression to covary for depression and posttraumatic stress disorder (PTSD), which is often comorbid with depression in Veteran populations.

There was a significant improvement in Digit Span Forward (p=.01, d=-.53), but not Digit Span Backward (p=.06) and Number Sequencing (p=.54) post-TMS treatment. Depression severity was not a significant predictor of performance on Digit Span Forward (f(1,5)=.29, p=.61) after TMS treatment. PTSD severity was also not a significant predictor of performance on Digit Span Forward (f(1,5)=1.31, p=.32).

Findings suggested that a standard course of TMS improves less demanding measures of working memory after a full course of TMS, but possibly not the more demanding aspects of working memory. This improvement in cognitive function was independent of improvements in depression and PTSD symptoms. Further investigation in a larger sample and with direct neuroimaging measures of cognitive function is warranted.

To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.

Prospective observational study.

Neonatal intensive care unit (NICU).

We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.

A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.

In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.

To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection.

Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020.

Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia.

HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic.

Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection.

Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3–14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient’s bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs).

In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Adults with ADHD describe self-medicating with cannabis. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from trials. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14-18.06.15, 30 participants were randomly assigned to the active (n=15) or placebo (n=15) group. For the primary outcome, no significant difference was found in the intent-to-treat analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est=-0.17,95%CI-0.40-0.07, p=0.16, n=15/11 active/placebo). For secondary outcomes Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity (p=0.03) and a cognitive measure of inhibition (p=0.05), and a trend towards improvement for inattention (p=0.10) and EL (p=0.11). Per-protocol effects were higher. Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. While not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD.

During this work-RC was a Ph.D. student funded by a grant to PA from Vifor Pharma. PA received funds (consultancy/sponsored talks/research/education) from Shire, Lilly, Novartis, Janssen, PCMScientific, Vifor Pharma, QBTech. Sativex was free from GW Pharm