Publications by authors named "Frederike Stein"

Article Synopsis
  • Large language models can capture changes in how words are understood in people with mental disorders by analyzing their semantic space, particularly looking at how word meanings relate.
  • Recent studies show a 'shrinking' semantic space in psychosis, where words tend to be more similar to each other in meaning.
  • In a study comparing patients with schizophrenia spectrum disorders and major depression to healthy controls, both clinical groups exhibited more restricted ways of navigating meaning, indicating changes in how they connect ideas compared to those without mental health issues.
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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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Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group.

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Deviations in syntax production have been well documented in schizophrenia spectrum disorders (SSD). Recently, we have shown evidence for transdiagnostic subtypes of syntactic complexity and diversity. However, there is a lack of studies exploring brain structural correlates of syntax across diagnoses.

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Article Synopsis
  • Schizophrenia (SCZ) shows differences in brain structure and symptoms between men and women, suggesting distinct neurobiological factors linked to sex.
  • The study analyzed MRI data from nearly 6,000 participants to explore the effects of sex and diagnosis on the shape of deep brain regions in individuals with SCZ compared to healthy controls.
  • Results indicated that women with SCZ had more pronounced shape abnormalities than men, but there were no significant interactions between diagnosis and sex, highlighting the need for further exploration of sex-related differences in schizophrenia's neurobiology.
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Background: Cognitive deficits are a key source of disability in individuals with major depressive disorder (MDD) and worsen with disease progression. Despite their clinical relevance, the underlying mechanisms of cognitive deficits remain poorly elucidated, hampering effective treatment strategies. Emerging evidence suggests that alterations in white matter microstructure might contribute to cognitive dysfunction in MDD.

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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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In the last two decades, numerous magnetic resonance imaging (MRI) studies have examined differences in cortical structure between individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) and healthy controls. These studies primarily emphasized alterations in gray matter volume (GMV) and cortical thickness (CT). Still, the scientific literature is notably scarce in regard to investigating associations of cortical structure with ADHD psychopathology, specifically inattention within adults with ADHD.

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Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.

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Article Synopsis
  • This study used machine learning to classify subtypes of schizophrenia by analyzing brain images from over 4,000 patients and healthy individuals through international collaboration.* -
  • Researchers identified two neurostructural subgroups: one with predominant cortical loss and enlarged striatum, and another with significant subcortical loss in areas like the hippocampus and striatum.* -
  • The findings suggest this new imaging-based classification could redefine schizophrenia based on biological similarities, enhancing our understanding and treatment of the disorder.*
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While most people are right-handed, a minority are left-handed or mixed-handed. It has been suggested that mental and developmental disorders are associated with increased prevalence of left-handedness and mixed-handedness. However, substantial heterogeneity exists across disorders, indicating that not all disorders are associated with a considerable shift away from right-handedness.

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Article Synopsis
  • - The ENIGMA Anxiety Working Group studied brain structural differences between individuals with specific phobias and healthy participants, focusing on subtypes of phobias like animal and blood-injection-injury (BII) while examining how these differences relate to symptom severity and age.
  • - A total of 1,452 participants with phobias and 2,991 healthy subjects were analyzed, revealing that those with phobias exhibited smaller subcortical volumes and varying cortical thickness, especially noted in adults rather than youths.
  • - The results indicate that brain alterations in specific phobias are more significant than in other anxiety disorders, revealing distinct neural underpinnings linked to fear processing across different phobia types, highlighting a
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Article Synopsis
  • - 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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Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures.

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Background: Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.

Methods: In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPI scale; = 208), patients with a DSM-IV-TR diagnosis of BD ( = 87), and healthy controls ( = 115) using voxel-based morphometry in SPM12/CAT12.

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Background: Neuroinflammation affects brain tissue integrity in multiple sclerosis (MS) and may have a role in major depressive disorder (MDD). Whether advanced magnetic resonance imaging characteristics of the gray-to-white matter border serve as proxy of neuroinflammatory activity in MDD and MS remain unknown.

Methods: We included 684 participants (132 MDD patients with recurrent depressive episodes (RDE), 70 MDD patients with a single depressive episode (SDE), 222 MS patients without depressive symptoms (nMS), 58 MS patients with depressive symptoms (dMS), and 202 healthy controls (HC)).

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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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Article Synopsis
  • Formal thought disorder (FTD) is a key symptom of schizophrenia, but its exact neurobiological causes and correlation with brain volume loss are still unclear, which this study seeks to address using a large cohort of patients and controls.
  • The research focuses on differentiating between positive, negative, and total formal thought disorder while investigating brain structural changes and their cellular bases using virtual histology tools.
  • Findings reveal distinct neural networks for positive and negative FTD, with negative FTD showing preserved orbitofrontal thickness and both FTD types linked to unique cellular fingerprint patterns, advancing our understanding of the disorder.
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  • This study looks at how stressful life events can lead to depression in people who might already be vulnerable to it.
  • They compared brain changes in people with depression to those without depression over two years.
  • They found that healthy people had some brain changes when stressed, but depressed people only showed changes when they had a history of tough childhood experiences and went through another episode of depression.
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Background: Depressive symptoms seem to be interrelated in a complex and self-reinforcing way. To gain a better understanding of this complexity, the inclusion of theoretically relevant constructs (such as risk and protective factors) offers a comprehensive view into the complex mechanisms underlying depression.

Methods: Cross-sectional data from individuals diagnosed with a major depressive disorder (N = 986) and healthy controls (N = 1049) were analyzed.

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Article Synopsis
  • * This large-scale study analyzed MRI scans from over 2,000 schizophrenia patients and 2,800 healthy controls to assess brain volume and microstructural integrity, using advanced modeling techniques.
  • * Results showed that aggressive behavior was significantly associated with reduced cortical and white matter volumes, particularly in key brain areas, suggesting a direct neurological link to aggression in schizophrenia patients.
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Article Synopsis
  • Schizophrenia is characterized by significant changes in brain structure, but it's not clear if these changes relate to the brain's network organization.
  • Researchers analyzed MRI scans from nearly 2,500 people with schizophrenia alongside healthy controls to see how structural changes connect to brain networks.
  • The study found that certain regions in the brain that are crucial for connectivity are more affected in schizophrenia, indicating a link between brain network vulnerability and the disease's impact, with some similarities to bipolar disorder but not major depressive disorder.
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