Publications by authors named "David C Glahn"

Phenotypic and genetic relationships between white matter microstructure (i.e., fractional anisotropy [FA]) and peripheral inflammatory responses (i.

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Copy-number variants (CNVs) that increase the risk for neurodevelopmental disorders also affect cognitive ability. However, such CNVs remain challenging to study due to their scarcity, limiting our understanding of gene-dosage-sensitive biological processes linked to cognitive ability. We performed a genome-wide association study (GWAS) in 258,292 individuals, which identified-for the first time-a duplication at 2q12.

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  • Research shows that gut dysbiosis is linked to psychiatric disorders like schizophrenia, but studies on adolescents with early-onset psychosis are scarce.
  • This study found specific gut bacteria that are more or less abundant in schizophrenia patients compared to non-psychotic individuals, as well as variations based on the type of antipsychotic treatment they received.
  • The analysis highlighted significant differences in enzymes related to fatty acid metabolism and identified differentially expressed genes, emphasizing the need to consider diet and gut microbiome in understanding the gut-brain connection in mental health.
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Stress contributes to transdiagnostic morbidity and mortality across a wide range of physical and mental health problems. VR tasks have been validated as stressors with robust effect sizes for VR-based stressors to evoke stress across the most common autonomic and adrenocortical stress biomarkers. However, meta-analytic validation of VR stressors have resulted in inconsistent logic: why should something that isn't real evoke a very real suite of stress responses? This review posits that conceptually addressing this question requires differentiating a cause, "stressor", from effects, "stress".

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Background: Early onset psychosis (EOP) frequently presents with a severe clinical phenotype and poor long-term prognosis. Clinical experience suggests that individuals with EOP have abnormal pain and somatosensory processing, yet relative to adult-onset psychosis, pain and somatic sensory processing in EOP have rarely been studied.

Methods: The history of two characteristic patients is described to illustrate clinical presentations of pain in EOP patients.

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Copy-number variants (CNVs) have been implicated in a variety of neuropsychiatric and cognitive phenotypes. We found that deleterious CNVs are less prevalent in non-European ancestry groups than they are in European ancestry groups of both the UK Biobank (UKBB) and a US replication cohort (SPARK). We also identified specific recurrent CNVs that consistently differ in frequency across ancestry groups in both the UKBB and SPARK.

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Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model.

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  • - We conducted a study on 7,140 Hispanic and Latino adults to identify genetic regions linked to cognitive abilities through admixture and fine-mapping analyses.
  • - We found nine regions in the genome associated with cognitive function, and three of these regions showed strong statistical evidence for supporting genes related to cognitive functioning and dementia.
  • - Our findings enhance the understanding of how ancestry influences cognitive abilities, showcasing the effectiveness of admixture mapping in identifying unique genetic variants relevant to cognitive function.
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  • Over 55 million people globally have dementia, with Alzheimer's Disease and Related Dementias (ADRD) constituting 60-70% of cases, leading to cognitive decline linked to neurodegeneration in key brain areas.
  • Research indicates that increased endoplasmic reticulum (ER) stress may contribute to ADRD pathology by disrupting neurocellular homeostasis, particularly in regions involved in learning and memory.
  • A study using induced pluripotent stem cell-derived neural stem cells found that ER stress, induced by thapsigargin, decreased NSC self-renewal and increased apoptosis, activating key UPR pathways that regulated gene expression and revealed significant changes in 2300 genes related to neurodegeneration.
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This review article was awarded the Dirk Hellhammer award from ISPNE in 2023. It explores the dynamic relationship between stressors and stress from a historical view as well as a vision towards the future of stress research via virtual reality (VR). We introduce the concept of a "syncytium," a permeable boundary that blurs the distinction between stress and stressor, in order to understand why the field of stress biology continues to inadequately measure stress alone as a proxy for the force of external stressors.

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Background: Portable low-field-strength magnetic resonance imaging (MRI) systems represent a promising alternative to traditional high-field-strength systems with the potential to make MR technology available at scale in low-resource settings. However, lower image quality and resolution may limit the research and clinical potential of these devices. We tested two super-resolution methods to enhance image quality in a low-field MR system and compared their correspondence with images acquired from a high-field system in a sample of young people.

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Asymmetry between the left and right hemisphere is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variants, which typically exert small effects on brain-related phenotypes.

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  • The study investigates how white matter (WM) microstructure develops and declines with age, creating reference curves to track these changes throughout the human lifespan using data from 40,898 subjects aged 3 to 95.
  • They employed diffusion MRI (dMRI) techniques and found that the ComBat-GAM method harmonized data most effectively, aligning with known WM maturation patterns.
  • The research also revealed that the ApoE4 gene, linked to dementia risk, affects WM microstructure even in healthy individuals, highlighting significant interactions between age and genetic factors across different brain regions.
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  • The study evaluates different normative models for analyzing brain structure data to find the most effective approach for research and clinical applications.
  • They tested eight algorithms using data from over 37,000 healthy individuals across multiple regions and identified multivariate fractional polynomial regression (MFPR) as the best-performing model.
  • The MFPR proved to be highly accurate across various age groups and maintains stability over time, offering valuable insights for understanding brain development and assisting in future research.
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  • * 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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We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates.

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Magnetic Resonance Imaging provides unprecedented images of the brain. Unfortunately, scanners and acquisition protocols can significantly impact MRI scans. The development of statistical methods able to reduce this variability without altering the relevant information in the scans, often coined harmonization methods, has been the topic of an increasing research effort supported by the recent growth of publicly available neuroimaging data sets and new possibilities for combining them to achieve greater statistical power.

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Background And Hypothesis: Structural brain alterations are well-established features of schizophrenia but they do not effectively predict disease/disease risk. Similar to polygenic risk scores in genetics, we integrated multifactorial aspects of brain structure into a summary "Neuroscore" and examined its potential as a marker of disease.

Study Design: We extracted measures from T1-weighted scans and diffusion tensor imaging (DTI) models from three studies with schizophrenia and healthy individuals.

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  • Carriers of specific genetic variants (1q21.1 distal and 15q11.2 BP1-BP2) show both regional and global brain structure differences compared to noncarriers, but analyzing these differences can be complicated.
  • The study used MRI data from various groups (carriers and noncarriers) to assess how regional brain characteristics diverge from overall brain structure differences.
  • Findings revealed that certain brain regions in carriers exhibited distinct patterns of cortical surface area and thickness that deviated from the global average, suggesting more complex effects of these genetic variants on brain development.
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  • CNVs are genetic variations that increase the risk of neurodevelopmental and psychiatric disorders, including autism and schizophrenia, impacting brain structures differently based on the specific CNV type.
  • A study was conducted using harmonized protocols on 675 CNV carriers and 782 controls, revealing that all CNVs affected subcortical brain structures like the hippocampus and amygdala, with unique subregional changes identifiable through shape analyses.
  • The results indicate that CNVs have varied effects on brain volume and cognition, with some clustering around adult-onset disorders while others align with autism, enhancing our understanding of the relationship between genetics and neuropsychiatric conditions.
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  • Psychiatry is leveraging digital phenotyping and AI/ML tools to analyze mental health by tracking various real-world data from participants, such as location, online activity, and health metrics.
  • Current ethical guidelines for sharing individual research results (IRRs) are insufficient to manage the sensitive data generated in this research.
  • An interdisciplinary expert group has created a new framework addressing the ethical, legal, and social issues of returning IRRs in digital phenotyping studies, which can also be applied to other medical research fields.
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Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of the most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes.

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  • * Researchers utilized the Variant Effect Predictor Algorithm to identify genes with ultra-rare variants linked to adult-onset schizophrenia and focused on a cohort of 34 EOP individuals.
  • * Findings revealed a significant increase in VEPHMI variants in the EOP group, with 20% of them carrying such variants, supporting the idea that these genetic factors may play a role in neuropsychiatric disorders.
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