A translational multimodal machine-learning prototype predicting valproate response in epilepsy treatment.

Epilepsy affects around 1% of the global population and often requires long-term treatment with antiseizure medications (ASMs). However, the current treatment strategy is based on clinical acumen and trial and error, resulting in only about 50% of patients remaining seizure-free for at least 12 months with first-line ASMs. Valproic acid (VPA) is a commonly prescribed first-line ASM, yet <50% of patients experience inadequate seizure control (ISC) or unacceptable adverse reactions (UARs), necessitating discontinuation.

Reprogramming Patient-Derived urine cells into iPSCs for Anti-GAD65 autoimmune encephalitis research.

Urine cells from a patient with anti-GAD65autoantibody-associated autoimmune limbic encephalitis (ALE) were reprogrammed intoiPSCline IUFi020-A. Pluripotency was confirmed throughhiPSCore analysis while G-banding and CNVanalysis demonstrated that IUFi020-A exhibits characteristic features of a bona fide iPSC line with no genetic changes compared to the donor urine cells. STRanalysis further confirmed that IUFi020-A was derived from the parental urine cells.

The transcriptomic signature of DEPDC5 KO induced mTOR hyperactivation in human neurons and its response to rapamycin treatment.

Objective: Mutations of the DEP Domain Containing 5 gene (DEPDC5), a mechanistic Target of Rapamycin (mTOR) inhibitor involved in amino acid sensing, are associated with neurological diseases such as epilepsy and/or autism spectrum disorder (ASD). Loss of DEPDC5 impacts early neuronal development via mTOR hyperactivity. Although, in the mTOR-hyperactivity-associated syndrome tuberous sclerosis, mTOR inhibitors have proven to be beneficial in treating epilepsy, ASD-associated symptoms are ameliorated only partially.

Transcriptomic decoding of surface-based imaging phenotypes and its application to pharmacotranscriptomics.

Imaging transcriptomics has become a power tool for linking imaging-derived phenotypes (IDPs) to genomic mechanisms. Yet, its potential for guiding CNS drug discovery remains underexplored. Here, utilizing spatially-dense representations of the human brain transcriptome, we present an analytical framework for the transcriptomic decoding of high-resolution surface-based neuroimaging patterns, and for linking IDPs to the transcriptomic landscape of complex neurotransmission systems in vivo.

Parsing Autism Heterogeneity: Transcriptomic Subgrouping of Imaging-Derived Phenotypes in Autism.

Background: Neurodevelopmental conditions, such as autism, are highly heterogeneous both at the mechanistic and phenotypic level. Parsing heterogeneity is therefore vital for uncovering underlying processes that could inform the development of targeted, personalized support. The study aimed to parse heterogeneity in autism by identifying subgroups that converge at both phenotypic and molecular levels.

Psychoneuroendocrine stress response in female and male youth with major depressive disorder.

Background: Exposure to psychosocial stress is one of the strongest risk factors for major depressive disorder (MDD) in youth, but underlying neurobiological mechanisms are poorly understood. Previous studies on the neuroendocrine stress response in youth with MDD are scarce, limited to cortisol, and rarely considered sex differences. Due to puberty-associated neuroendocrine transitions increasing the risk for MDD onset in adolescence, this study aimed to investigate sex-specific stress responses of stress and sex hormones as well as of neuropeptides.

Dual Role of microRNA-146a in Experimental Inflammation in Human Pulmonary Epithelial and Immune Cells and Expression in Inflammatory Lung Diseases.

microRNA (miR)-146a emerges as a promising post-transcriptional regulator in various inflammatory diseases with different roles for the two isoforms miR-146a-5p and miR-146a-3p. The present study aimed to examine the dual role of miR-146a-5p and miR-146a 3p in the modulation of inflammation in human pulmonary epithelial and immune cells in vitro as well as their expression in patients with inflammatory lung diseases. Experimental inflammation in human A549, HL60, and THP1 via the NF-kB pathway resulted in the major upregulation of miR-146a-5p and miR-146a-3p expression, which was partly cell-specific.

Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial.

Introduction: Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called "Adappt," aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health.

MicroRNA Profiling of the Inflammatory Response after Early and Late Asthmatic Reaction.

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma's pathology.

Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis.

Interferon regulatory factor 4 (IRF4) is a master transcription factor that regulates T helper cell (Th) differentiation. It interacts with the Basic leucine zipper transcription factor, ATF-like (BATF), depletion of which in CD4 T cells abrogates acute graft-versus-host disease (aGVHD)-induced colitis. Here, we investigated the immune-regulatory role of in a mouse model of MHC-mismatched bone marrow transplantation.

Admission rates and clinical profiles of children and youth with eating disorders treated as inpatients before and during the COVID-19 pandemic in a German university hospital.

Introduction: Children and youth at risk for mental health disorders, such as eating disorders (ED), were particularly affected by the COVID-19 pandemic, yet evidence for the most seriously affected and thus hospitalized youth in Germany is scarce.

Methods: This crosssectional study investigated anonymized routine hospital data (demographic information, diagnoses, treatment modalities) of patients admitted ( = 2,849) to the Department of Child and Adolescence Psychiatry, Psychosomatics and Psychotherapy (DCAPPP) of a German University Hospital between 01/2016 and 02/2022. Absolute and relative number of inpatients with or without ED prior to (01/2016-02/2020) and during the COVID-19 pandemic (03/2020-02/2022) were compared.

Association between Polyunsaturated Fatty Acid Profile and Bronchial Inflammation in Bronchiolitis Obliterans.

Introduction: Bronchiolitis obliterans (BO) is a chronic lung disease, which occurs after an insult to the lower airways, in particular after airway infections or after stem cell transplantation, and which results in persistent inflammation. -3 and -6 polyunsaturated fatty acids (PUFA) have been shown to influence the inflammatory processes in chronic inflammatory conditions. Since BO is maintained by persistent pulmonary inflammation, a disbalanced -6/-3 fatty acid profile could support the inflammatory process in patients with BO and therefore, could become an approach to new therapeutic options.

Generation of four human induced pluripotent stem cells derived from ADHD patients carrying different genotypes for the risk SNP rs1397547 in the ADHD-associated gene ADGRL3.

Single nucleotide polymorphisms (SNPs) in the ADGRL3 gene have been significantly associated with the development of ADHD, the aetiology of which remains poorly understood. The rs1397547 SNP has additionally been associated with significantly altered ADGRL3 transcription. We therefore generated iPSCs from two wild type ADHD patients, and two ADHD patients heterozygous for the risk SNP.

Association of polygenic risk scores and hair cortisol with mental health trajectories during COVID lockdown.

The COVID-19 pandemic is a global stressor with inter-individually differing influences on mental health trajectories. Polygenic Risk Scores (PRSs) for psychiatric phenotypes are associated with individual mental health predispositions. Elevated hair cortisol concentrations (HCC) and high PRSs are related to negative mental health outcomes.

ADHD-associated PARK2 copy number variants: A pilot study on gene expression and effects of supplementary deprivation in patient-derived cell lines.

Recent studies show an association of Parkin RBR E3 ubiquitin protein ligase (PARK2) copy number variations (CNVs) with attention deficit hyperactivity disorder (ADHD). The aim of our pilot study to investigate gene expression associated with PARK2 CNVs in human-derived cellular models. We investigated gene expression in fibroblasts, hiPSC and dopaminergic neurons (DNs) of ADHD PARK2 deletion and duplication carriers by qRT PCR compared with healthy and ADHD cell lines without PARK2 CNVs.

Effects of Hypoxia on RNA Cargo in Extracellular Vesicles from Human Adipose-Derived Stromal/Stem Cells.

Mesenchymal stromal/stem cells and their derivates are the most promising cell source for cell therapies in regenerative medicine. The application of extracellular vesicles (EVs) as cell-free therapeuticals requires particles with a maximum regenerative capability to enhance tissue and organ regeneration. The cargo of mRNA and microRNA (miR) in EVs after hypoxic preconditioning has not been extensively investigated.

The methylome in females with adolescent Conduct Disorder: Neural pathomechanisms and environmental risk factors.

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts.

Translating the Role of mTOR- and RAS-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.

Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD.

The MiR-320 Family Is Strongly Downregulated in Patients with COVID-19 Induced Severe Respiratory Failure.

A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure ( = 11) and severe respiratory failure ( = 10) at an acute stage (day 0-3) and in the later course of the disease (>7 days).

SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study.

Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual's sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes.

[Genetic risk factors and their influence on neural development in autism spectrum disorders].

Genetic risk factors and their influence on neural development in autism spectrum disorders Abstract. Autism spectrum disorders are etiologically based on genetic and specific gene x biologically relevant environmental risk factors. They are diagnosed based on behavioral characteristics, such as impaired social communication and stereotyped, repetitive behavior and sensory as well as special interests.

DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.