Thomas G. Schulze

Thomas G. Schulze
Ludwig-Maximilians-Universität in Munich | LMU · Institute of Psychiatric Phenomics and Genomics (IPPG)

Doctor of Medicine

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741
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Publications

Publications (741)
Preprint
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Objective: Lithium augmentation (LA) is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies could yield novel insights into treatment prediction to enable personalized therapy choices. Here, we investigated the effects o...
Article
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Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, thei...
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Background Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains. Aims We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether...
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Older Adults with Bipolar Disorder (OABD) represent a heterogeneous group, including those with early and late onset of the disorder. Recent evidence shows both groups have distinct clinical, cognitive, and medical features, tied to different neurobiological profiles. This study explored the link between polygenic risk scores (PRS) for bipolar diso...
Article
Duplications of the Xq28,distal locus have been described in male and female patients with schizophrenia (SCZ) or intellectual disability. The Xq28,distal locus spans eight protein‐coding genes ( F8 , CMC4 , MTCP1 , BRCC3 , VBP1 , FUNDC2 , CLIC2 , and RAB39B ) and is flanked by recurrent genomic breakpoints. Thus, the issue of which gene/s at this...
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Zusammenfassung Die vorliegende Arbeit bietet Einblicke in die Rolle genetischer Diagnostik bei psychischen Erkrankungen im Erwachsenenalter. Die Bedeutung genetischer Faktoren in der Entstehung psychischer Erkrankungen und seltener genetischer Syndrome bis hin zu häufigen komplex-genetischen Erkrankungen wird beschrieben. Aktuelle wegweisende klin...
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Human induced pluripotent stem cells (hiPSCs) are an invaluable tool to study molecular mechanisms on a human background. Culturing stem cells at an oxygen level different from their microenvironmental niche impacts their viability. To understand this mechanistically, dermal skin fibroblasts of 52 probands were reprogrammed into hiPSCs, followed by...
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Many bipolar disorder (BD) patients are non-responsive to lithium. The mechanisms underlying lithium (non-)responsiveness are largely unknown. By using gene-set enrichment analysis methods, we found that core clock gene-sets are significantly associated with lithium response. Among the top hits was BHLHE41, a modulator of the molecular clock and ho...
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Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk...
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Background Human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCM) could be a helpful tool to study the physiology and diseases of the human atrium. To fulfill this expectation, the electrophysiology of hiPSC-aCM should closely resemble the situation in human atrium. Data on the contribution of the slowly activating delayed re...
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Micro RNAs (miRNAs) play a crucial role as regulators of various biological processes and have been implicated in the pathogenesis of mental disorders such as schizophrenia and bipolar disorders. In this study, we investigate the expression patterns of miRNAs in the PsyCourse Study (n=1,786), contrasting three broad diagnostic groups: Psychotic (Sc...
Poster
Background Most people at elevated risk for a mental disorder will never develop it. This has led to the investigation of plausible protective mechanisms in these individuals that would help them remain healthy despite their genetic burden. Recently, a genome-wide association study (GWAS) for schizophrenia resilience was developed capturing the pro...
Article
Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregul...
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Accurate clustering of mixed data, encompassing binary, categorical, and continuous variables, is vital for effective patient stratification in clinical questionnaire analysis. To address this need, we present longmixr, a comprehensive R package providing a robust framework for clustering mixed longitudinal data using finite mixture modeling techni...
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Research on people deprived of liberty raises serious questions, especially concerning behavioral genetic studies. Does including criminally detained patients with mental disorders in genetic studies lead to a gain of new knowledge and can this be ethically and legally justified? Evaluation of existing literature and interdisciplinary reflection. A...
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Zusammenfassung Hintergrund Intensivmedizinische Aufenthalte führen bei vorbelasteten Menschen häufig zu Symptomen einer posttraumatischen Belastungsstörung (Post-ICU-PTBS). In der Nachsorge spielen HausärztInnen eine wichtige Rolle. Falldarstellung Eine 58-jährige Patientin entwickelt nach erlebter Sepsis eine Post-ICU-PTBS. Sie erhält durch ihr...
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The field of psychiatric genetics has evolved rapidly over the past decades, leading to major advancements in our understanding of the genetic architecture of mental disorders. Dozens of genes have been definitively linked to neurodevelopmental disorders (NDDs), and hundreds of genetic loci have been significantly associated with psychiatric dis...
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Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inad...
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Primary carnitine deficiency (PCD) is an autosomal recessive monogenic disorder caused by mutations in SLC22A5. This gene encodes for OCTN2, which transports the essential metabolite carnitine into the cell. PCD patients suffer from muscular weakness and dilated cardiomyopathy. Two OCTN2-defective human induced pluripotent stem cell lines were gene...
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Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose o...
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Genome-wide association studies have unearthed a wealth of genetic associations across many complex diseases. However, translating these associations into biological mechanisms contributing to disease etiology and heterogeneity has been challenging. Here, we hypothesize that the effects of disease-associated genetic variants converge onto distinct...
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Background and hypothesis: Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemp...
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Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication...
Preprint
Full-text available
Schizophrenia is a psychiatric disorder that is still not readily treatable. Pharmaceutical advances in the treatment of schizophrenia have mainly focused on the protein coding part of the human genome. However, the vast majority of the human transcriptome consists of non-coding RNAs. MicroRNAs are small non-coding RNAs that control the transcripto...
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As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cogni...
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Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers. Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in...
Preprint
Full-text available
Schizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analy...
Article
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorders (SZ) exhibit considerable phenotypic and genetic overlap. However, the contribution of genetic factors to their shared psychopathological symptom dimensions remains unclear. The present exploratory study investigated genetic contributions to the symptom dim...
Article
Background: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. M...
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A popular approach to reduce the high dimensionality resulting from genome-wide association studies is to analyze a whole pathway in a single test for association with a phenotype. Kernel machine regression (KMR) is a highly flexible pathway analysis approach. Initially, KMR was developed to analyze a simple phenotype with just one measurement per...
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Over the last few years, extracellular vesicles (EVs) have received increasing attention as potential non-invasive diagnostic and therapeutic biomarkers for various diseases. The interest in EVs is related to their structure and content, as well as to their changing cargo in response to different stimuli. One of the potential areas of use of EVs as...
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Bipolar disorder (BD) is a complex mood disorder with a strong genetic component. Recent studies suggest that microRNAs contribute to psychiatric disorder development. In BD, specific candidate microRNAs have been implicated, in particular miR-137 , miR-499a , miR-708 , miR-1908 and miR-2113 . The aim of the present study was to determine the contr...
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Introduction New insights into the pathophysiology of mental disorders and innovations in psychiatric care depend on the availability of representative, longitudinal and multidimensional datasets across diverse, transdiagnostic populations. Biobanks usually attempt to collect such data in parallel to clinical routine, which is resource-intensive, p...
Preprint
Full-text available
Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship of medication adherenc...
Article
Full-text available
Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was...
Preprint
Full-text available
Primary carnitine deficiency (PCD) is an autosomal recessive monogenic disorder caused by mutations in SLC22A5. This gene encodes for OCTN2 which transports the essential metabolite carnitine into the cell. PCD patients suffer from muscular weakness and dilated cardiomyopathy. Detailed molecular disease mechanisms remain unclear. Two OCTN2-defectiv...
Article
Full-text available
This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 di...
Article
Lithium is an effective mood stabilizer in bipolar disorder (BD). There is, however, high variability in treatment response to lithium and only 20-30% of individuals with BD are excellent responders. This subgroup has been shown to have specific phenotypic characteristics, and family studies have implicated genetics as an important factor. However,...
Article
Biological research and clinical management in psychiatry face two major impediments: the high degree of overlap in psychopathology between diagnoses and the inherent heterogeneity with regard to severity. Here, we aim to stratify cases into homogeneous transdiagnostic subgroups using psychometric information with the ultimate aim of identifying in...
Preprint
Full-text available
Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was...
Article
IMPORTANCE No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers. OBJECTIVE To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in ass...
Article
Full-text available
The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventi...
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Background To date, besides genome-wide association studies, a variety of other genetic analyses (e.g. polygenic risk scores, whole-exome sequencing and whole-genome sequencing) have been conducted, and a large amount of data has been gathered for investigating the involvement of common, rare and very rare types of DNA sequence variants in bipolar...
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Background Case-only longitudinal studies are common in psychiatry. Further, it is assumed that psychiatric ratings and questionnaire results of healthy controls stay stable over foreseeable time ranges. For cognitive tests, improvements over time are expected, but data for more than two administrations are scarce. Aims We comprehensively investig...
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Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients ( N = 3012) using fixed- and random-effects inverse variance-weighted meta-ana...