Publications by authors named "Bertram Muller-Myhsok"

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

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Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

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Early life stress (ELS) can negatively impact health, increasing the risk of stress-related disorders, such as post-traumatic stress disorder (PTSD). Importantly, PTSD disproportionately affects women, emphasizing the critical need to explore how sex differences influence the genetic and metabolic neurobiological pathways underlying trauma-related behaviors. This study uses the limited bedding and nesting (LBN) paradigm to model ELS and investigate its sex-specific effects on fear memory formation.

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  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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  • - The study aimed to explore the genetic basis of major depressive disorder by analyzing symptoms across various clinical and community cohorts, acknowledging challenges like sample size differences and missing data patterns.
  • - Researchers performed genome-wide association studies using data from both diagnosed and undiagnosed participants, fitting models to understand the relationships between different depressive symptoms.
  • - Findings emphasized the relevance of symptom directionality (e.g., hypersomnia vs. insomnia) and the necessity of considering study design when analyzing genetic data related to depression.
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  • - Stratified medicine aims to customize treatment for individuals based on their unique needs, with genetics playing a key role, but current methods like polygenic risk scores (PRS) have limitations in clinical usefulness and biological relevance.
  • - The newly developed CASTom-iGEx method addresses these shortcomings by analyzing how genetic risk factors impact gene expression in specific tissues, resulting in the identification of diverse patient biotypes in conditions like coronary artery disease and schizophrenia.
  • - Unlike PRS, the CASTom-iGEx approach reveals biologically significant and clinically actionable subgroups of patients, suggesting that different biotypes are linked to specific disease mechanisms, thus enhancing the future of personalized medicine.
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The response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial.

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Background: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments.

Methods: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival.

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  • Accurately diagnosing bipolar disorder (BD) can take around 7 years due to its overlap with unipolar major depressive disorder (MDD), especially since the first manic episode often follows a depressive one.
  • This study uses genome-wide association analyses (GWAS) and polygenic risk scores (PRS) from a large cohort to identify genetic factors that could help differentiate between BD and MDD early on.
  • The results show that while BD and MDD are genetically distinct and share a continuum of genetic risk, larger future studies are needed to enhance the accuracy of these genetic predictors for early diagnosis.
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Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD.

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Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This pipeline first adopts sparse multiple canonical correlation analysis to select multi-view features possibly informed by extraneous data, which are then used to construct individual-specific networks (ISNs).

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Background: There has been extensive research into adverse childhood experiences (ACEs), however, less consideration has been given to the prevalence and impact of ACEs for staff working with people with intellectual disabilities.

Method: Participants were staff employed by agencies that care for people with intellectual disabilities. An online survey collected demographic information and measures of ACEs, resilience, trauma-informed organisational climate, burnout and secondary traumatic stress.

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Severe stress exposure increases the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and behavioral changes.

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  • Major depressive disorder shows varied symptoms, and genetic analysis can help identify specific subtypes and clinical profiles.
  • Challenges in integrating symptom data arise from differences in sample sizes and patterns of missing data in clinical vs. community groups.
  • The study used genome-wide association studies to find that a model including unique symptom factors and accounting for missing data best represented the symptoms of depression, highlighting the need to consider symptom directionality and study design when analyzing genetic data.
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Background: Different observations have suggested that patients with depression have a higher risk for a number of comorbidities and mortality. The underlying causes have not been fully understood yet.

Aims: The aim of our study was to investigate the association of a genetic depression risk score (GDRS) with mortality [all-cause and cardiovascular (CV)] and markers of depression (including intake of antidepressants and a history of depression) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study involving 3,316 patients who had been referred for coronary angiography.

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Social behavior is naturally occurring in vertebrate species, which holds a strong evolutionary component and is crucial for the normal development and survival of individuals throughout life. Behavioral neuroscience has seen different influential methods for social behavioral phenotyping. The ethological research approach has extensively investigated social behavior in natural habitats, while the comparative psychology approach was developed utilizing standardized and univariate social behavioral tests.

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  • Genome-wide association studies have identified numerous genetic links to complex diseases, but understanding how these links affect the biology of diseases remains difficult.
  • The authors propose that genetic variants influence specific molecular pathways in different patient groups, leading to diverse clinical outcomes.
  • Their new CASTom-iGEx pipeline helps analyze genetic data to uncover individual risk factors and disease mechanisms, showing that genetic variations can create distinct patient profiles linked to different pathways and disease severities.
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Multi-view data offer advantages over single-view data for characterizing individuals, which is crucial in precision medicine toward personalized prevention, diagnosis, or treatment follow-up. Here, we develop a network-guided multi-view clustering framework named netMUG to identify actionable subgroups of individuals. This pipeline first adopts sparse multiple canonical correlation analysis to select multi-view features possibly informed by extraneous data, which are then used to construct individual-specific networks (ISNs).

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  • Therapeutic approaches in psychiatry aim to affect the brain's dynamic network transitions, and Network Control Theory helps quantify how one brain region can influence others in this context.
  • A study using Diffusion Tensor Imaging data analyzed brain connectivity in 692 major depressive disorder (MDD) patients and 820 healthy controls, revealing differences in network controllability that aren't linked to current symptoms.
  • The research found that network controllability in MDD patients is associated with genetic risk factors, family history of mood disorders, and individual characteristics like body mass index, highlighting its potential for personalized mental health treatment strategies.
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  • * A genome-wide association study (GWAS) involving over 13,000 to 33,000 participants revealed significant associations in word reading linked to specific genetic markers, while accounting for 13-26% of the variability in various language-related traits.
  • * The research indicates a shared genetic factor among several language skills and establishes connections to brain structure associated with language processing, emphasizing the role of genetics in understanding human language abilities.
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Background: Predicting treatment outcome in major depressive disorder (MDD) remains an essential challenge for precision psychiatry. Clinical prediction models (CPMs) based on supervised machine learning have been a promising approach for this endeavor. However, only few CPMs have focused on model sparsity even though sparser models might facilitate the translation into clinical practice and lower the expenses of their application.

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Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case-control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip.

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  • * Researchers discovered 287 genomic regions associated with schizophrenia, emphasizing genes specifically active in excitatory and inhibitory neurons, and identified 120 key genes potentially responsible for these associations.
  • * The findings highlight important biological processes related to neuronal function, suggesting overlaps between common and rare genetic variants in both schizophrenia and neurodevelopmental disorders, ultimately aiding future research on these conditions.
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