Faculty Bibliography

INTRODUCTION/BACKGROUND:Underlying causes of Alzheimer's disease (AD) remain unknown, making it imperative to identify molecular mechanisms driving the pathobiology of AD onset and progression. METHODS:Laser capture microdissection was used to isolate layer III pyramidal neurons from post mortem human prefrontal cortex (Brodmann area 9). Single population RNA sequencing was conducted using tissue from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. Differentially expressed genes (DEGs) were compared across groups. RESULTS:DEGs increased from prodromal (MCI vs. NCI) to progression (AD vs. MCI) to frank AD (AD vs. NCI). The majority of DEGs and pathways shared between prodromal and progression exhibited a change in the direction of dysregulation unlike pathways between progression and frank AD. DISCUSSION/CONCLUSIONS:Candidate genes and pathways were identified that demarcate early-stage AD onset from AD progression, providing a roadmap to study cortical cellular vulnerability and key targets for intervention at early stages of AD. HIGHLIGHTS/CONCLUSIONS:Pyramidal neuron differentially expressed genes (DEGs) are directionally divergent between prodromal, progression, and frank Alzheimer's disease (AD). Pyramidal neuron DEGs are directionally convergent between progression and frank AD. Dysfunctional bioenergetic pathways increased dysregulation as the AD spectrum progressed. Immune response pathways were more dysregulated in frank AD than prodromal stages. DEGs, = biological pathways, and interactomes demarcate specific stages across the AD spectrum.

Altered fetal brain function is proposed as a mechanism underlying the relationship between prenatal maternal depression (PMD) and neurodevelopmental outcomes in offspring. This study investigated the association between PMD symptoms and fetal brain functional connectivity (FC) using graph theory. A total of 123 pregnant women participated in the study, completed the Center for Epidemiologic Studies Depression Scale (CES-D), and underwent fetal MRI scans. Results revealed a significant relationship between elevated PMD symptoms and reduced global efficiency in the right insular region of the fetal brain. However, because fetal age was not associated with local or global efficiency in the insular brain region, we cannot determine if the PMD-related reduction in insula global efficiency is indicative of an accelerated or delayed developmental pattern. This study is one of the few to examine fetal brain connectivity in relation to prenatal maternal depression, providing valuable insights into early neurodevelopmental risks and potential targets for early intervention.

BACKGROUND/OBJECTIVES/OBJECTIVE:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies with a challenging prognosis, especially for patients with Neurofibromatosis type 1 (NF1). Their low incidence necessitates comprehensive studies to investigate the survival outcome. METHODS:We conducted a systematic review and meta-analysis, including data from 16 studies and 4265 patients, to explore surgical outcomes and survival rates, focusing on time-related outcomes, including overall survival (OS), progression-free survival (PFS), and recurrence rate. RESULTS:The analysis revealed that the OS rate was 86% [95% CI: 75-97%] at 1 year, decreasing to 60% [95% CI: 45-75%] at 3 years, and further declining to 47% [95% CI: 35-58%] by 5 years. For PFS, the 1-year rate was 61% [95% CI: 25-98%], which remained similar at 62% [95% CI: 35-89%] for 3 and 5 years. In NF1-associated MPNSTs, the 1-year OS was relatively high at 93% [95% CI: 83-100%], but it dropped to 68% [95% CI: 53-84%] at 3 years and further to 50% [95% CI: 31-68%] at 5 years. Additionally, the hazard ratio indicated a 38% lower survival rate in NF1 patients than those with sporadic MPNSTs when data were presented in the same study. Recurrence rates were high, with 56% of patients experiencing a relapse, primarily as local recurrences (70.6%). Mortality was significant, with over 50% of patients dying within an average follow-up period of 33.45 months. CONCLUSIONS:MPNSTs, particularly in NF1 patients, are associated with poor prognosis and high recurrence rates. These results underline the necessity of targeted therapeutic strategies and improved programs for screening, mainly through a multidisciplinary approach to optimize management.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

This umbrella review synthesizes data on the prevalence of mental disorder symptoms among university students worldwide. A systematic search of seven databases (inception-July 23, 2023) followed PRISMA guidelines. We included meta-analyses assessing the prevalence of mental disorder symptoms, evaluating methodological quality with AMSTAR-2. A random-effects meta-analysis was conducted, along with meta-regression and subgroup analyses for moderators (percentage of females, publication date, healthcare-related degrees, COVID-19 pandemic). We included 1,655 primary studies from 62 meta-analyses, encompassing 8,706,185 participants. AMSTAR-2 ratings classified 35 % of meta-analyses as low quality and 65 % as critically low. Pooled prevalence estimates were: depression-mild (35.41 %, CI=33.9-36.93) and severe (13.42 %, CI=8.03-19.92; k=952; n=2,108,813); anxiety-mild (40.21 %, CI=37.39-43.07) and severe (16.79 %, CI=7.21-29.29; k=433; n=1,579,780); sleep disorders (41.09 %, CI=35.7-46.58); eating disorders (17.94 %, CI=15.79-20.20); gambling disorder (6.59 %, CI=5.52-7.75); post-traumatic stress disorder (25.13 %, CI=20.55-30.02); stress (36.34 %, CI=29.36-43.62); and suicide-related outcomes (ideation past 12 months: 10.76 %, CI=9.53-12.06; lifetime ideation: 20.33 %, CI=16.15-24.86; suicide attempt past 12 months: 1.37 %, CI=0.67-2.29; lifetime attempt: 3.44 %, CI=2.48-4.54). Meta-regression analyses identified statistically significant moderators of prevalence such as healthcare academic degrees and the pandemic in the case of depression and studies with more females in the case of sleep disorders. This is the most comprehensive synthesis on the prevalence of mental disorder symptoms in university students, providing crucial insights for clinicians, policymakers, and stakeholders.

BACKGROUND:) that underlies the vulnerability to both physical and mental conditions could have important implications for our approach to health assessment and treatment. OBJECTIVE:in children and adolescents. METHODS:This Swedish registry-based cross-sectional study included children and adolescents born between 1996 and 2003 with follow-up until 2013. We extracted data on 25 mental and physical health conditions according to the ICD-10 system. To determine the optimal dimensional structure of these conditions, several competing measurement models were tested, including correlated factors, one factor, various bifactor specifications and bifactor exploratory structural equation modelling (ESEM). FINDINGS/RESULTS:=0.423; ECV=0.130) factors also indicated additional significant unique contributions. CONCLUSIONS:underlying both mental and physical conditions, alongside distinct domain-specific factors. These findings have important implications for clinical practice, providing evidence that suggests the need for more integrated approaches to health assessment and treatment that consider the interconnectedness of mental and physical health.

OBJECTIVE:Real-time imaging is useful for the evaluation of wrist instability. However, currently available real-time magnetic resonance imaging (MRI) methods are limited due to their 2D nature or provide insufficient temporal resolution and image quality for quantitative kinematic analysis. This work introduces a novel approach for volumetric dynamic MRI of the wrist joint during active motion and demonstrates the feasibility of tracking carpal bone motion. MATERIALS AND METHODS/METHODS:A flexible 8-element 3 T wrist receive coil and 3D-printed support platform for guiding motion were designed for dynamic wrist imaging. 2D real-time images were acquired using a fat-saturated FLASH sequence with radial sampling and reconstructed with the GRASP algorithm. Corresponding volumetric dynamic wrist images were obtained by assembling 2D real-time images into 3D snapshots using autodetected MRI-visible markers for slice alignment. The proposed method was demonstrated for radial-ulnar deviation on five healthy volunteers. RESULTS:The flexible wrist coil provided high SNR while allowing a wide range of wrist movements. 2D real-time wrist images were acquired with a temporal resolution of 48 ms/frame with negligible streaking artifacts. Carpal bones and metacarpal bones were properly aligned in the assembled dynamic volumes for all five subjects. The excellent bone-to-tissue contrast enabled accurate segmentation of the individual carpal bones on the assembled dynamic volumes. CONCLUSION/CONCLUSIONS:This work introduces a novel wrist coil and demonstrates that real-time volumetric dynamic examination of the moving wrist is feasible. The achieved image quality and high temporal resolution could enable automatic segmentation of carpal bones and quantitative kinematic assessment for evaluating wrist instability.

BACKGROUND:Disordered eating in early adolescence impacts development, with long-term health implications. Minoritised adolescents might be at higher risk of disordered eating due to minority stress, but most research has focused on White, heterosexual, cisgender individuals; less is known about disordered eating among minoritised adolescents. We examined sexual, gender, racial, and ethnic identities in relation to disordered eating in early adolescence. METHOD/METHODS:Using 2-year follow-up data from adolescents ages 10-14 in the Adolescent Brain Cognitive Development Study (N = 9385), we examined associations between sexual, gender, racial, and ethnic identities and past-2 week disordered eating (preoccupation with weight, weight control behaviors, and binge eating). RESULTS:Compared to heterosexual peers, gay/bisexual adolescents had higher odds of all three outcomes (AOR 1.90-3.32); those "questioning" their sexual identity had higher odds of preoccupation with weight (AOR 1.82) and binge eating (AOR 2.53). Compared to cisgender adolescents, transgender adolescents had higher odds of binge eating (AOR 2.62); those "questioning" their gender identity had higher odds of preoccupation with weight (AOR 2.45). Adolescents whose racial identity was categorised as "Another" had higher odds of preoccupation with weight (AOR 1.46) and weight control behaviors (AOR 1.58) compared to White adolescents. Finally, Hispanic adolescents had higher odds of all disordered eating outcomes than non-Hispanic adolescents (AOR 1.25-1.59). DISCUSSION/CONCLUSIONS:This study is among the first to reveal disparities in disordered eating among minoritised early adolescents. Further examination of these disparities can inform future interventions. Healthcare providers are encouraged to screen for disordered eating, recognising that minoritised early adolescents may be at risk.