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.

A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.

We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.

We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.

Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.

Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.

We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.

We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.

The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.

Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.

To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT).

We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact.

We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017–August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11–4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11–3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83–1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact.

Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.

Alterations in cerebral blood flow (CBF) are associated with risk of cognitive decline and Alzheimer’s disease (AD). Although apolipoprotein E (APOE) ε4 and greater vascular risk burden have both been linked to reduced CBF in older adults, less is known about how APOE ε4 status and vascular risk may interact to influence CBF. We aimed to determine whether the effect of vascular risk on CBF varies by gene dose of APOE ε4 alleles (i.e., number of e4 alleles) in older adults without dementia.

144 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) underwent arterial spin labeling (ASL) and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure assessment. Vascular risk was assessed using pulse pressure (systolic blood pressure -diastolic blood pressure), which is thought to be a proxy for arterial stiffening. Participants were classified by number of APOE ε4 alleles (n0 alleles = 87, m allele = 46, n2 alleles = 11). CBF in six FreeSurfer-derived a priori regions of interest (ROIs) vulnerable to AD were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regression models tested the interaction between categorical APOE ε4 dose (0, 1, or 2 alleles) and continuous pulse pressure on CBF in each ROI, adjusting for age, sex, cognitive diagnosis (cognitively unimpaired vs. mild cognitive impairment), antihypertensive medication use, cerebral metabolism (FDG-PET composite), reference CBF region (precentral gyrus), and AD biomarker positivity defined using the ADNI-optimized phosphorylated tau/ß-amyloid ratio cut-off of > 0.0251 pg/ml.

A significant pulse pressure X APOE ε4 dose interaction was found on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex (ps < .005). Among participants with two e4 alleles, higher pulse pressure was significantly associated with lower CBF (ps < .001). However, among participants with zero or one ε4 allele, there was no significant association between pulse pressure and CBF (ps > .234). No significant pulse pressure X APOE ε4 dose interaction was found in the inferior temporal cortex, rostral middle frontal gyrus, or medial orbitofrontal cortex (ps > .109). Results remained unchanged when additionally controlling for general vascular risk assessed via the modified Hachinski Ischemic Scale.

These findings demonstrate that the cross-sectional association between pulse pressure and region-specific CBF differs by APOE ε4 dose. In particular, a detrimental effect of elevated pulse pressure on CBF in AD-vulnerable regions was found only among participants with the e4/e4 genotype. Our findings suggest that pulse pressure may play a mechanistic role in neurovascular unit dysregulation for those genetically at greater risk for AD. Given that pulse pressure is just one of many potentially modifiable vascular risk factors for AD, future studies should seek to examine how these other factors (e.g., diabetes, high cholesterol) may interact with APOE genotype to affect cerebrovascular dysfunction.

Recent studies have begun to explore the role of psychological resilience in pediatric mTBI recovery, with findings associating higher levels of resilience with shorter recovery and lower levels of resilience mediated by pre-injury anxiety and depression associated with persistent symptoms. The purpose of this study is to extend the current literature by further exploring the relationship between resilience, post-injury emotional changes, and length of recovery from pediatric mTBI. Based upon previous literature, we predicted that resilience would explain a unique portion of the variance in length of recovery above and beyond acute post-injury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls.

The current study pulled data from a larger project utilizing a prospective cohort design in two cohorts of high school student-athletes aged 14-18 (N = 32). Participants with mTBI (n = 17) or OI (n = 15) sustained during sport were recruited within 10 days of injury from a quaternary care setting. Participants completed a neuropsychological screening evaluation within one week of enrollment, including self-report rating scales of resilience (Connor-Davidson Resilience Scale-10; CD-RISC) and self- and parent-reported post-concussion symptoms (Post-Concussion Symptom Inventory, Second Edition; PCSI-2). Hierarchical regression analysis was performed with days from injury to recovery as the dependent variable. Predictors were entered in three steps: (1) group (mTBI/OI) and sex, (2) PCSI self- and parent-reported post-injury change in emotional symptoms, and (3) CD-RISC raw score. Bonferroni correction was utilized to control for multiple comparisons.

Group and sex did not provide significant prediction when entered into the first block of the model (p= .61). Introducing PCSI emotional ratings in the second block showed statistically significant improvement, F (2,26) = 5.12, p< .01), accounting for 31% of the variance in recovery length. Addition of the CD-RISC in the third block was not statistically significant (p=.59). Post hoc testing indicated parent ratings on the PCSI were significantly associated with recovery length t(32) = 3.16, p < .01, while self-reported ratings were not (p=.54).

Findings indicated that psychological resilience did not explain a unique portion of the variance in length of recovery above and beyond acute parent report of postinjury emotional symptoms in adolescents recovering from mTBI compared with orthopedic injured (OI) controls. Interestingly, sex, group (mTBI vs. OI), and self-reported acute postinjury emotional symptoms were not significant predictors of recovery length in this sample. Results highlight the significant role of acute changes in emotional symptoms in adolescents recovering from mTBI and OI in predicting length of recovery, as well as the importance of obtaining separate caregiver report. A more robust understanding of factors contributing to recovery from injury can help inform and improve preventive measures and treatment plants for those at risk or impacted; however, psychological resilience may not uniquely contribute to predicting length of recovery in acutely injured adolescents, limiting value added to the clinical exam. Future studies should explore the relationship between type of injury and recovery time in larger samples.

Children with congenital heart disease (CHD) have increased likelihood for Autism Spectrum Disorder (AuSD; Sigmon, Kelleman, Susi, Nylung & Oster, 2020). Even those not meeting full criteria remain at greater risk for problems with social processing/communication (Cassidy et al, 2018). The current study examined what symptoms indicative of potential AuSD were qualitatively reported by parents, and what symptoms were noted behaviorally by clinicians. These behaviors may be targets for both further clinical inquiry and intervention.

A retrospective chart review of CHD patients seen for neuropsychological assessment between the ages of 6-18 years and between 2016-2021 was conducted. The final sample included 88 patients (Ethnicity: 14% Hispanic; Race: 76% White, 17% Black/African American, 5% Asian, 1% Native American, 1% Unknown). A coding system for AuSD symptoms was derived by the authors, who are experienced in AuSD diagnosis and assessment, based on DSM-5 criteria. A comprehensive list of behaviors consistent with each symptom category was generated, and assessment reports were subsequently reviewed noting the presence, absence or “no mention” of each symptom. A second coding system was derived to assess for AuSD symptoms documented in each report’s behavioral observations. Three pediatric neuropsychologists, one post-doctoral fellow, and one psychometrist were coders, with very good reliability (k=.854 (95% CI, .827 to .881), p < .0001).

Twelve patients (14%) were diagnosed with AuSD. Age of diagnosis ranged from 3-14 years (M=7.82, SD=3.92). Main concerns parents expressed included difficulty with reciprocal conversation (75%), making friends (75%), initiating and maintaining social interactions (67%), and restrictive/intense interests (58%). During testing, providers noted variable eye contact (67%), appropriate responses to questions but minimal social conversation (67%), and exaggerated prosody (42%). Of those who did not have an AuSD diagnosis, the most frequent parent concerns included difficulty making friends (38%), difficulty initiating or maintaining social interactions (33%), atypical affect (25%), and restrictive/intense interests (18%). In this sample, providers noted concerns with answering questions but not maintaining conversation (26%), flat affect (16%), loud (17%) or soft (21%) speech volume, and socially immature behaviors (10%). Within this No Diagnosis group, general social concerns were highly correlated (point biserial) with more specific autism symptoms (e.g., intense interests, difficulty with transitions, sensory sensitivities r = .986 - .784), although most often the presence or absence of these concerns were not documented.

We examined qualitative parent-reported and provider-observed behaviors indicative of potential AuSD as detailed in a comprehensive neuropsychological evaluation report. Behaviors in children with formal AuSD diagnoses were consistent with that diagnosis, based on both parent and provider description. Of note, in children without AuSD, though, both parents and providers reported AuSD-like concerns (e.g., social communication/interaction problems, atypical interests, atypical affect, atypical speech volume) in a large minority of children. It is important that if general social concerns are present, that providers follow-up on, and document, a broader constellation of AuSD symptoms. These behaviors deserve further exploration and study within the CHD population and are important areas of inquiry in any clinical evaluation, as they should directly inform intervention.

Evidence-based consensus in children and adolescents following uncomplicated mTBI indicates acute cognitive symptoms resolve over time with minimal long-term impact. However, traditional paper-and-pencil neuropsychological measures used in many studies have been criticized for lacking sensitivity to subtle changes in attention and executive functions. The National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) is a computerized tool assessing overall cognition, fluid cognition, and crystallized cognition with few studies in pediatric mTBI. The aim of this study is to continue to explore the utility of the NIHTB-CB in adolescents recovering from mTBI compared to orthopedic injuries (OI) and healthy controls (HC).

The current pilot study utilized a prospective cohort design with longitudinal follow-up in three cohorts of high school student-athletes aged 14-18 (N= 52). Participants with mTBI (n= 17) or OI (n= 15) sustained during sport were recruited within 10 days of injury from a quaternary care setting. An age- and gender-matched cohort of healthy controls (HC) in an active sport season was included for community comparison (n= 20). The NIHTB-CB was administered as part of a neuropsychological screening battery at enrollment and one month after medical clearance (mTBI and OI) or eight weeks after enrollment (HC).

Results of a 3(group) x 2(time) ANOVA revealed a main effect of time (p < .001), but not group (p = .06), on the overall Fluid Cognition Composite. The mTBI group showed significantly lower performance on a measure of attention/inhibitory control (Flanker) compared to healthy controls acutely post-injury (p = .04; d = 0.72) and following clinical recovery (p < .01; d = 0.98), with no decline observed in the magnitude of group differences over time. The mTBI and OI groups exhibited deficits in performance on a measure of cognitive flexibility (Dimensional Change Card Sort) compared to the HC group acutely post-injury (both p < .01; d = 1.09-0.93). The magnitude of group differences between the OI and HC groups declined over time (p > .05; d = 0.68), whereas the mTBI group continued to show significantly lower performance following clinical recovery compared to the HC group (p = .02; d = 0.81). The mTBI, OI, and HC groups did not exhibit significant differences in working memory, explicit memory, or processing speed acutely post-injury and following clinical recovery (all p > .05; all d = 0.52 - 0.05). No significant effects of group (p = .16), time (p = .67), or the interaction (p = .45) were found on the Crystalized Cognition Composite.

Adolescents with mTBI demonstrated deficits on the NIHTB-CB measures of attention and executive functions acutely post-injury and extending beyond clinical recovery compared with healthy controls in this study. These subtle yet persistent deficits in cognitive performance lend support to the growing body of literature suggesting that alterations in neurotransmission may persist beyond resolution of clinical symptoms of mTBI. Further work is needed in larger samples to better understand trends in cognitive deficits and to identify clinical correlates persisting beyond clinical recovery from mTBI.

Urine-culture diagnostic stewardship aims to decrease misdiagnosis of urinary tract infections (UTIs); however, these interventions are not widely adopted. We examined UTI diagnosis and management practices to identify barriers to and facilitators of diagnostic stewardship implementation.

Using a qualitative descriptive design, we conducted semistructured interviews at 3 Veterans’ Affairs medical centers. Interviews were conducted between November 2021 and May 2022 via Zoom videoconferencing using an interview guide and visual prototypes of proposed interventions. Interviewees were asked about current practices and thoughts on proposed interventions for urine-culture ordering, processing, and reporting. We used a rapid analysis matrix approach to summarize key interview findings and compare practices and perceptions across sites.

We interviewed 31 stakeholders and end users. All sites had an antimicrobial stewardship program but limited initiatives targeting appropriate diagnosis and management of UTIs. The majority of those interviewed identified the importance of diagnostic stewardship. Perceptions of specific interventions ranged widely by site. For urine-culture ordering, all 3 sites agreed that documentation of symptomology would improve culturing practices but did not want it to interrupt workflow. Representatives at 2 sites expressed interest in conditional urine-culture processing and 1 was opposed. All sites had similar mechanisms to report culture results but varied in perceptions of the proposed interventions. Feedback from end users was used to develop a general diagnostic stewardship implementation checklist.

Interviewees thought diagnostic stewardship was important. Qualitative assessment involving key stakeholders in the UTI diagnostic process improved understanding of site-specific beliefs and practices to better implement interventions for urine-culture ordering, processing, and reporting.

Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome.

157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−).

We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change.

Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis.

The study objective was to determine the feasibility of training physicians in the principles of the National Incident Management System (NIMS) and Incident Command System (ICS) as applied to in-hospital rapid responses and to assess physicians’ attitudes regarding rapid responses.

This was an educational pilot study. Resident physicians completed a pre-survey, followed by online training in the principles of NIMS and ICS, a knowledge test, and a post-survey.

The number of residents who participated was 22. In the pre-survey, most (20/22) did not have a working understanding of NIMS/ICS. Participants (21/22) agreed that residents should have more training in resource organization. On the knowledge test, the median score was 9.5/10. In the post-survey, participants felt more comfortable clearing extra resources from the scene (P < 0.001) and that it would be easier to keep track of resources (P < 0.001). Most indicated that they had a working understanding of NIMS/ICS (P < 0.001) and felt more comfortable establishing command using NIMS/ICS (P < 0.001). All agreed that they would consider using an NIMS/ICS-based structure on their next rapid response.

Training physicians in the principles of NIMS/ICS as they pertain to rapid responses is feasible and appears to change residents’ attitudes about rapid responses.

Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence.

Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment.

A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04–0.15) and functional impairment (ΔR2 = 0.01–0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06–0.15; functional impairment: ΔR2 = 0.05–0.12).

Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.