Publications by authors named "Forstner A"

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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Disorders across the affective disorders-psychosis spectrum such as major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SCA), and schizophrenia (SCZ), have overlapping symptomatology and high comorbidity rates with other mental disorders. So far, however, it is largely unclear why some of the patients develop comorbidities. In particular, the specific genetic architecture of comorbidity and its relationship with brain structure remain poorly understood.

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  • Duplications of a specific region on the X chromosome known as Xq28,distal have been linked to schizophrenia (SCZ) and intellectual disability in both males and females, though the exact genes involved remain unclear.
  • This study aimed to explore rare genetic variants in the Xq28,distal locus and how they might contribute to SCZ risk, using advanced sequencing methods on a large sample of patients and controls.
  • Despite identifying some potentially functional variants, the analysis did not find a significant difference between patients with SCZ and controls, suggesting that more research is needed to understand the role of X-chromosomal factors in neuropsychiatric disorders.
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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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Introduction: Early recognition and indicated prevention is a promising approach to decrease the incidence of Major depressive episodes (MDE), targeting the patients during their clinical high-risk state of MDE (CHR-D). The identification of a set of stressors at the CHR-D increases the success of indicated prevention with personalized early interventions. The study evaluated stressors in the early phase of depression, developed on the basis of a patient survey on stressors.

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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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A previously published genome-wide association study (GWAS) meta-analysis across eight neuropsychiatric disorders identified antagonistic single-nucleotide polymorphisms (SNPs) at eleven genomic loci where the same allele was protective against one neuropsychiatric disorder and increased the risk for another. Until now, these antagonistic SNPs have not been further investigated regarding their link to brain structural phenotypes. Here, we explored their associations with cortical surface area and cortical thickness (in 34 brain regions and one global measure each) as well as the volumes of eight subcortical structures using summary statistics of large-scale GWAS of brain structural phenotypes.

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This review article provides insights into the role of genetic diagnostics in adult mental health disorders. The importance of genetic factors in the development of mental illnesses, from rare genetic syndromes to common complex genetic disorders, is described. Current clinical characteristics that may warrant a genetic diagnostic work-up are highlighted, including intellectual disability, autism spectrum disorders and severe psychiatric conditions with specific comorbidities, such as organ malformations or epilepsy.

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Resilience is the capacity to adapt to stressful life events. As such, this trait is associated with physical and mental functions and conditions. Here, we aimed to identify the genetic factors contributing to shape resilience.

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  • Structural neuroimaging studies reveal both common and disorder-specific gray matter deficits across various psychiatric conditions.
  • Large-scale data pooling helps identify potential neuroanatomical factors linked to mental illness vulnerability, although data-sharing faces significant challenges.
  • Using a federated analysis across eight research sites, the study found overlapping gray matter patterns in schizophrenia, major depressive disorder, and autism spectrum disorder, suggesting shared cortical and subcortical vulnerabilities.
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Background: Social Anxiety Disorder (SAD) is a highly heterogeneous disorder. To enlighten its heterogeneity, this study focused on recalled parental behavior and aimed to empirically identify if there are subgroups of SAD based on recalled parental behavior by means of cluster analysis. Further, the study investigated whether those subgroups differed on clinical, trauma, and personality variables.

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  • * A genome-wide association meta-analysis of nearly 122,000 ANX cases revealed 58 significant genetic variants and 66 related genes, with many of these findings replicated in a larger independent sample.
  • * The findings indicate a substantial genetic overlap between ANX and other conditions like depression, emphasizing GABAergic signaling as a key mechanism, thereby enhancing our understanding of the genetic basis of ANX for future research.
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  • - The study explores the connections between dimensional psychopathological syndromes and brain structure/function in patients with Major Depressive Disorder, Bipolar Disorder, Schizoaffective Disorder, and Schizophrenia, analyzing data from 1,038 individuals.
  • - Researchers identified three main psychopathological factors—paranoid-hallucinatory syndrome, mania, and depression—and found significant brain volume and cortical thickness differences linked to the paranoid-hallucinatory syndrome.
  • - Genome-wide association studies revealed significant genetic associations for mania and depression, suggesting a need for more dimensional perspectives in psychiatric classifications to improve understanding and treatment.
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  • Understanding how antidepressants work at a molecular level can lead to better therapies that people tolerate well.
  • The study analyzed DNA methylation changes linked to antidepressant use across multiple cohorts, using blood samples and data collected between 2006 and 2011.
  • Results showed specific DNA regions with increased methylation in individuals using antidepressants, with findings suggesting connections to brain-related genes and providing insights for further research on treatment effectiveness.
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Reduced processing speed is a core deficit in major depressive disorder (MDD) and has been linked to altered structural brain network connectivity. Ample evidence highlights the involvement of genetic-immunological processes in MDD and specific depressive symptoms. Here, we extended these findings by examining associations between polygenic scores for tumor necrosis factor-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in a large sample of MDD patients.

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Aim: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK.

Methods: We used PRSice-v2.

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Purpose: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents.

Participants: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition).

Findings To Date: To date, four publications on both genetic and environmental risk and resilience factors (including , glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample.

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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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  • Lithium is the primary treatment for bipolar disorder (BD), but how it works and predicts outcomes is not fully understood.
  • A previous study identified key cellular pathways linked to lithium response, including focal adhesion and PI3K-Akt signaling.
  • In this new study, researchers confirmed these pathways in a larger group of 2039 patients but found no connection with the extracellular matrix, suggesting that issues with neuronal growth signaling may impact lithium effectiveness.
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Patients with bipolar disorder (BD) show alterations in both gray matter volume (GMV) and white matter (WM) integrity compared with healthy controls (HC). However, it remains unclear whether the phenotypically distinct BD subtypes (BD-I and BD-II) also exhibit brain structural differences. This study investigated GMV and WM differences between HC, BD-I, and BD-II, along with clinical and genetic associations.

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  • Angioedema is a serious reaction linked to ACE inhibitors, and its causes include genetic and non-genetic factors; recent studies have begun to uncover genetic risk factors but not the full underlying mechanisms.!* -
  • Researchers analyzed data from over 1,000 European patients, discovering three significant genetic risk loci associated with ACEi-induced angioedema, one of which has not been previously noted.!* -
  • The findings underscored the role of bradykinin signaling and coagulation pathways while suggesting new genetic candidates involved in angioedema, highlighting similar genetic effects in both European and African-American patients.!*
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Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no informative biomarkers have been identified.

Objective: To evaluate whether machine learning (ML) can identify a multivariate biomarker for MDD.

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