Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer

Qiu, Lin; Jiang, Hao; Cho, Kevin; Yu, Yanbo; Jones, Lynne A.; Huang, Tianyu; Perlmutter, Joel S.; Gropler, Robert J.; Brier, Matthew R.; Patti, Gary J.; Benzinger, Tammie L. S.; Tu, Zhude

doi:10.1021/acschemneuro.4c00077

Cited by 2 publications

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Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity

Dolatshahi,

Commean,

Rahmani

et al. 2024

Obesity

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ObjectiveThis study investigated how obesity, BMI ≥ 30 kg/m2, abdominal adiposity, and systemic inflammation relate to neuroinflammation using diffusion basis spectrum imaging.MethodsWe analyzed data from 98 cognitively normal midlife participants (mean age: 49.4 [SD 6.2] years; 34 males [34.7%]; 56 with obesity [57.1%]). Participants underwent brain and abdominal magnetic resonance imaging (MRI), blood tests, and amyloid positron emission tomography (PET) imaging. Abdominal visceral and subcutaneous adipose tissue (VAT and SAT, respectively) was segmented, and Centiloids were calculated. Diffusion basis spectrum imaging parameter maps were created using an in‐house script, and tract‐based spatial statistics assessed white matter differences in high versus low BMI values, VAT, SAT, insulin resistance, systemic inflammation, and Centiloids, with age and sex as covariates.ResultsObesity, high VAT, and high SAT were linked to lower axial diffusivity, reduced fiber fraction, and increased restricted fraction in white matter. Obesity was additionally associated with higher hindered fraction and lower fractional anisotropy. Also, individuals with high C‐reactive protein showed lower axial diffusivity. Higher restricted fraction correlated with continuous BMI and SAT particularly in male individuals, whereas VAT effects were similar in male and female individuals.ConclusionsThe findings suggest that, at midlife, obesity and abdominal fat are associated with reduced brain axonal density and increased inflammation, with visceral fat playing a significant role in both sexes.image

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Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity

Dolatshahi,

Commean,

Rahmani

et al. 2024

Obesity

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Polygenic Risk Scores Provide Strong Evidence for the Biologic Relevance of Molecular Subtypes of Schizophrenia

Rhodes,

Granger

2024

Preprint

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We have previously described how the post-mortem DLPFC transcriptomes of schizophrenia patients can be used to define two patient groups: “Type 1” patients with a relatively normal DLPFC transcriptome and “Type 2” patients with hundreds of genes differentially expressed in the DLPFC at a statistical significance which survives Bonferroni correction. The biological significance of the distinction between Type 1 and Type 2 patients remains an open question. In the present report we examine the schizophrenia polygenic risk scores (PRS) in those two groups of schizophrenic patients and observe that PRS account for twice the variance in schizophrenia risk in the patients with a relatively normal DLPFC transcriptome (“Type 1”) compared to those with dramatically abnormal DLPFC transcriptomes (“Type 2”). That result supports the hypothesis that the DLPFC transcriptome-defined schizophrenia subtypes are biologically meaningful.As important as that result is, a serendipitous observation involving patient ancestry is potentially more important because it suggests an approach which future studies might use to investigate the pathogenic pathways leading to these two distinct forms of schizophrenia. Summary statistics from the Psychiatric Genetics Consortium (PGC) wave 3 core cohort GWAS data were used to calculate schizophrenia PRS. That cohort is composed primarily of Caucasians with about 13% Asians. It contains no Africans or African Americans. However, the cohort we studied here (the NIMH Human Brain Collection Core, or HBCC cohort) is composed of roughly 50% Caucasians and 50% African Americans. When the HBCC cohort is stratified based on ancestry it becomes obvious that in African Americans the polygenic risk scores based on summary statistics from the (Caucasian) PGC core cohort capture the genetic risk associated with Type 1, but not Type 2 schizophrenia. Future work comparing summary statistics from schizophrenia GWAS studies of Caucasian and African American populations should reveal the genes and genetic pathways which are specifically involved in the pathogenesis of the two types of schizophreniaDisclosuresThe opinions expressed herein are those of the authors and not necessarily representative of those of the Uniformed Services University of the Health Sciences (USU), the Department of Defense (DOD), the United States Army, Navy, Air Force, VA, NIH or any other US federal agency.

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Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer

Cited by 2 publications

References 38 publications

Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity

Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity

Polygenic Risk Scores Provide Strong Evidence for the Biologic Relevance of Molecular Subtypes of Schizophrenia

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