Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.

The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.

This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.

Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.

Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.

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.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Epilepsy is one of the most common serious brain illness, with symptoms influenced by multiple risk factors and a strong genetic predisposition, rather than having a single expression and cause¹. Neuropsychiatric symptoms in epilepsy can encompass manifestations such as mood alterations, anxiety, sleep disturbances, psychosis, and behavioral disorders. While the motor and sensory manifestations of epileptic seizures are widely recognized, neuropsychiatric symptoms accompanying epilepsy are often underestimated. Therefore, it is essential to understand the most prevalent epidemiological profile of these patients to improve the diagnosis and management of these symptoms.

Our goal was to evaluate the neuropsychiatric behavior of epilepsy patients in Brazilian over the past 3 years through hospitalization data in order to outline an epidemiological and behavioral profile.

A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals simultaneously diagnosed with epilepsy, schizotypal and delusional disorders, and mood disorders in all five regions of Brazil (South, Southeast, Midwest, North, and Northeast) between February 2020 and December 2022. Data from January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of care, age range, gender, and ethnicity of the patients.

The analysis covers the years 2020 to 2022, totaling 503,045 hospitalizations. In 2022, the highest number of cases occurred (≈ 37.55%), followed by 2021 (≈ 33.62%) and 2020 (≈ 28.81%). Urgent hospitalizations represented ≈ 90.85% of the total. The most affected age group was 30 to 39 years old (≈ 18.30%). Men were more affected than women (≈ 52.03% and ≈ 47.96%, respectively), and Caucasians accounted for ≈ 36.07% of the hospitalizations. The average length of stay was 19.1 days, and the mortality rate was 1.4%.

Thus, there is a gradual and annual increase in the number of hospitalizations during the observed period. While there is a minimal disparity between the affected genders, it is evident that the profile of male, caucasian, and adult patients is the most prevalent. Moreover, the predominantly urgent nature of hospitalizations points to an alarming scenario regarding this issue. From the analysis of the data obtained in the study, there is a clear need for interventions capable of reducing the prevalence of hospitalizations for neuropsychiatric symptoms in epilepsy patients in Brazil.

None Declared

Neuropsychiatric disorders are the leading cause of disability worldwide, as seen in cases such as depression, anxiety, bipolar mood disorder and schizophrenia, which can be developed or exacerbated by the use of psychoactive substances. Most mental disorders have an early onset, often leading to early and/or permanent disability, increasing the need and cost of healthcare. Therefore, it is necessary to improve the identification of the epidemiological profile of these cases in the South of Brazil in order to enhance the diagnosis and reduce the costs associated with managing these disorders.

The present study aimed to analyze statistical data regarding hospitalizations related to mental disorders caused by the use of psychoactive substances and alcohol in the southern region of Brazil, highlighting the pathological scenario and identifying the most prevalent profiles of these disorders in this region.

A cross-sectional, descriptive, retrospective, and quantitative study was conducted on hospitalizations of individuals diagnosed with mental and behavioral disorders due to the use of psychoactive substances and alcohol in the states of the Southern region of Brazil (Paraná, Santa Catarina, and Rio Grande do Sul) between February 2020 and December 2022. Data of January 2020 were not available. The data used were collected through the Department of Health Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, gathering information regarding the nature of the care, age range, gender, and ethnicity of the patients.

The study covers the years 2020 to 2022, indicating a total of 81,608 hospitalizations, with the year 2022 having the highest number of cases (≈ 37.13%), followed by 2021 (≈ 33.30%) and 2020 (≈ 29.55%). The states with the highest number of hospitalizations were Rio Grande do Sul (≈ 54.90%), Paraná (≈ 29.29%), and Santa Catarina (≈ 15.79%). Urgent hospitalizations accounted for ≈ 87.29% of the total. The most affected age group was 30 to 39 years old (≈ 25.61%). Men were more affected than women (≈ 81.70% and ≈ 18.28%, respectively). Caucasians accounted for ≈ 64.29% of the hospitalizations. The average length of stay was 20.8 days, and the mortality rate was 0.32%.

There is a clear increase in the number of hospitalizations related to mental disorders caused by the use of psychoactive substances in the period from 2020 to 2022 in the southern region of Brazil, with the highest number of cases in the state of Rio Grande do Sul. The most affected population consisted of Caucasian men aged 30 to 39 years old. Furthermore, these results may be related to the increasing trend of psychoactive substance use among the Brazilian population and also the COVID-19 pandemic, which led to a period of underreporting due to social isolation.

None Declared

In recent years, mental health has gained prominence in public health, prompting thorough investigations into psychiatric condition trends. This study conducts a comprehensive epidemiological analysis of hospitalizations for Schizophrenia, Schizotypal, and Delirium Disorders in Rio Grande do Sul (RS) over the past five years. By revealing these patterns, it enhances our understanding of regional mental health dynamics and offers insights for intervention strategies, resource planning, and improved mental healthcare. The ultimate goal is to advance more effective and accessible mental healthcare in RS and beyond.

This study aims to analyze the prevalence and epidemiological profile of hospitalizations due to psychiatric disorders to assist in the diagnosis and outcome of affected patients.

A cross-sectional, descriptive, retrospective, and quantitative study was conducted regarding hospitalizations for Schizophrenia, Schizotypal Disorders, and Delirium in the state of RS between January 2018 and November 2022. Data were collected from the Department of Informatics of the Brazilian Unified Health System (DATASUS) in the “Hospital Information System of SUS” section, focusing on the nature of care, age group, gender, and ethnicity of the patients. The information was aggregated over the five-year period based on the four mentioned descriptors and subsequently analyzed to establish a profile of hospitalizations during that period.

The analysis spans from 2018 to 2022, encompassing a total of 28,345 hospitalizations. In 2019, there was the highest number of cases (22.21%), followed by 2018 (21.08%). Urgent care admissions constituted 85.34% of the total. The age group most affected was 35 to 39 years (11.8%). Men were more affected than women (60.18%), and the majority of hospitalizations were among the Caucasian ethnicity (75.12%). The average length of stay was 23.7 days, and the mortality rate stood at 0.26%.

The increasing trend in hospitalizations, peaking in 2019, highlights the need for preventive measures. Urgent admissions (85.34%) underscore the demand for accessible mental health resources. Men in the 35 to 39 age group are disproportionately affected, suggesting specific risk factors. The predominance of Caucasian ethnicity emphasizes the need for culturally sensitive care. A longer average length of stay (23.7 days) underscores treatment complexity, while a low mortality rate (0.26%) signals effective medical care. In essence, these findings inform tailored mental health policies to enhance service quality and prioritize patient-centered approaches.

None Declared

Poor cardiovascular health occurs with age and is associated with increased dementia risk, yet its impact on frontotemporal lobar degeneration (FTLD) and autosomal dominant neurodegenerative disease has not been well established. Examining cardiovascular risk in a population with high genetic vulnerability provides an opportunity to assess the impact of lifestyle factors on brain health outcomes. In the current study, we examined whether systemic vascular burden associates with accelerated cognitive and brain aging outcomes in genetic FTLD.

166 adults with autosomal dominant FTLD (C9orf72 n= 97; GRN n= 34; MAPT n= 35; 54% female; Mage = 47.9; Meducation = 15.6 years) enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Longitudinal FTD study (ALLFTD) were included. Participants completed neuroimaging and were screened for cardiovascular risk and functional impairment during a comprehensive neurobehavioral and medical interview. A vascular burden score (VBS) was created by summing vascular risk factors (VRS) [diabetes, hypertension, hyperlipidemia, and sleep apnea] and vascular diseases (VDS) [cerebrovascular disease (e.g., TIA, CVA), cardiac arrhythmia (e.g., atrial fibrillation, pacemaker, defibrillator), coronary artery disease (e.g., myocardial infarction, cardiac bypass, stent), and congestive heart failure] following a previously developed composite (range 0 to 8). We examined the interaction between each vascular health metric (VBS, VDS, VRS) and age (vascular health*age) on clinical severity (CDR plus NACC FTLD-SB), and white matter hyperintensity (WMH) volume outcomes, adjusting for age and sex. Vascular risk, disease, and overall burden scores were examined in separate models.

There was a statistically significant interaction between total VBS and age on both clinical severity (ß=0.20, p=0.044) and WMH burden (ß=0.20, p=0.032). Mutation carriers with higher vascular burden evidenced worse clinical and WMH outcomes for their age. When breaking down the vascular burden score into (separate) vascular risk (VRS) and vascular disease (VDS) scores, the interaction between age and VRS remained significant only for WMH (ß=0.26, p=0.009), but not clinical severity (ß=0.04, p=0.685). On the other hand, the interaction between VDS and age remained significant only for clinical severity (ß=0.20, p=0.041) but not WMH (ß=0.17, p=0.066).

Our results demonstrate that systemic vascular burden is associated with an “accelerated aging” pattern on clinical and white matter outcomes in autosomal dominant FTLD. Specifically, mutation carriers with greater vascular burden show poorer neurobehavioral outcomes for their chronological age. When separating vascular risk from disease, risk was associated with higher age-related WMH burden, whereas disease was associated with poorer age-related clinical severity of mutation carriers. This pattern suggests preferential brain-related effects of vascular risk factors, while the functional impact of such factors may be more closely aligned with fulminant vascular disease. Our results suggest cardiovascular health may be an important, potentially modifiable risk factor to help mitigate the cognitive and behavioral disturbances associated with having a pathogenic variant of autosomal dominant FTLD. Future studies should continue to examine the neuropathological processes underlying the impact of cardiovascular risk in FTLD to inform more precise recommendations, particularly as it relates to lifestyle interventions.