Siamak MahmoudianDehkordi
A5072914653- Metabolomics and Mass Spectrometry Studies
- Tryptophan and brain disorders
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Drug Transport and Resistance Mechanisms
- Gut microbiota and health
- Treatment of Major Depression
- Peroxisome Proliferator-Activated Receptors
- Liver Disease Diagnosis and Treatment
- Folate and B Vitamins Research
- Mental Health Research Topics
- Metabolism and Genetic Disorders
- Pharmacological Effects and Toxicity Studies
- Stress Responses and Cortisol
- Cholesterol and Lipid Metabolism
- Nutrition, Genetics, and Disease
- Tea Polyphenols and Effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Bioinformatics and Genomic Networks
- Nutritional Studies and Diet
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Trace Elements in Health
- Fatty Acid Research and Health
- Schizophrenia research and treatment
Duke University
2018-2025
North Carolina State University
2016-2023
North Central State College
2016-2023
Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut‐brain axis neurodegeneration. Bile acids (BAs), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer's disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1464 subjects including 370 cognitively...
Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic...
Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests microbiota influence pathological features Alzheimer's disease (AD) including neuroinflammation amyloid-β deposition.Serum levels 20 primary secondary BA metabolites from AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed association BAs with "A/T/N" (amyloid, tau, neurodegeneration) biomarkers for AD:...
<h3>Importance</h3> Increasing evidence suggests an important role of liver function in the pathophysiology Alzheimer disease (AD). The is a major metabolic hub; therefore, investigating association with AD, cognition, neuroimaging, and CSF biomarkers would improve understanding dysfunction AD. <h3>Objective</h3> To examine whether markers are associated cognitive "A/T/N" (amyloid, tau, neurodegeneration) for <h3>Design, Setting, Participants</h3> In this cohort study, serum-based were...
Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes identify genes in alternative acid synthesis pathway to be expressed brain. A targeted metabolomic analysis acids measured from samples 111 individuals supports these results. Our metabolic network that taurine transport, synthesis, metabolism differ AD cognitively normal...
Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large differences. We systematically investigated group-specific alterations by conducting stratified association analyses of 139 serum metabolites 1,517 individuals from the Neuroimaging Initiative with biomarkers. observed substantial differences effects 15 partially overlapping status groups. Several...
Importance Metabolomics reflect the net effect of genetic and environmental influences thus provide a comprehensive approach to evaluating pathogenesis complex diseases, such as depression. Objective To identify metabolic signatures major depressive disorder (MDD), elucidate direction associations using mendelian randomization, evaluate interplay human gut microbiome metabolome in development MDD. Design, Setting Participants This cohort study used data from participants UK Biobank (n = 500...
Abstract Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action not fully understood and therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing panel 180 metabolites to gain insights into response citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study...
Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide transcriptome-wide association studies identified various genes genetic variants lipid that are associated with However, the molecular mechanisms disruption remain to be determined. We focus on sphingolipid pathway carry out multi-omics analyses identify central peripheral metabolic changes patients, correlating them imaging features. Our approach is based (a) 2114 human...
The gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid that synthesized liver from cholesterol and further processed by gut-bacterial enzymes, thus requiring both human enzymatic processes their metabolism. BAs participate range important host functions such as lipid transport metabolism, cellular signaling regulation energy homeostasis. have recently been implicated pathophysiology...
Abstract Metabolome reflects the interplay of genome and exposome at molecular level thus can provide deep insights into pathogenesis a complex disease like major depression. To identify metabolites associated with depression we performed metabolome-wide association analysis in 13,596 participants from five European population-based cohorts characterized for depression, circulating using ultra high-performance liquid chromatography/tandem accurate mass spectrometry (UHPLC/MS/MS) based...
Abstract This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive (MDD), as defined by Diagnostic Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The also examined influence medication use, particularly antidepressants anxiolytics, classified through Anatomical Therapeutic Chemical (ATC) Classification System, on microbiota. Both 16S rRNA gene amplicon sequencing (16S)...
Abstract Metabolomics provides valuable tools for the study of drug effects, unraveling mechanism action and variation in response due to treatment. In this we used electrochemistry-based targeted metabolomics gain insights into mechanisms escitalopram/citalopram focusing on a set 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 8 weeks The 17-item Hamilton Depression Rating Scale (HRSD 17...
Abstract Alzheimer’s disease (AD) is the most common neurodegenerative presenting major health and economic challenges that continue to grow. Mechanisms of are poorly understood but significant data point metabolic defects might contribute pathogenesis. The Alzheimer Disease Metabolomics Consortium (ADMC) in partnership with Neuroimaging Initiative (ADNI) creating a comprehensive biochemical database for AD. Using targeted non- metabolomics lipidomics platforms we mapping pathway network...
Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, been implicated to play a significant role metabolic of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish three phenotypic subtypes major depressive disorder (MDD): core depression (CD+), anxious (ANX+), neurovegetative symptoms melancholia (NVSM+). Depressed outpatients (n = 240) from Mayo Clinic Pharmacogenomics Research Network were...
Abstract Combination antidepressant pharmacotherapies are frequently used to treat major depressive disorder (MDD). However, there is no evidence that machine learning approaches combining multi-omics measures (e.g., genomics and plasma metabolomics) can achieve clinically meaningful predictions of outcomes combination pharmacotherapy. This study examined data from 264 MDD outpatients treated with citalopram or escitalopram in the Mayo Clinic Pharmacogenomics Research Network Antidepressant...
Abstract Metabolomics in the Alzheimer’s Disease Neuroimaging Initiative cohort provides a powerful tool for mapping biochemical changes disease, and unique opportunity to learn about association between circulating blood metabolites brain amyloid-β deposition disease. We examined 140 serum their associations with deposition, cognition conversion from mild cognitive impairment disease Initiative. Processed [18F] Florbetapir PET images were used perform voxel-wise statistical analysis of...
Alzheimer's disease (AD) risk and progression are significantly influenced by APOE genotype with APOE4 increasing APOE2 decreasing susceptibility compared to APOE3. While the effect of those genotypes was extensively studied on blood metabolome, less is known about their impact in brain. Here we investigated impacts aging brain metabolic profiles across lifespan, using human APOE-targeted replacement mice. Biocrates P180 targeted metabolomics platform used measure a broad range metabolites...
Abstract Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes BAs AD development remains elusive. Here, authors quantitatively determined 33 58 BA features 4 219 samples collected from 1 180 participants Disease Neuroimaging Initiative. The findings revealed that these exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early late mild cognitive...
Abstract Introduction Altered lipid metabolism is implicated in Alzheimer's disease (AD), but the mechanisms remain obscure. Aging‐related declines circulating plasmalogens containing omega‐3 fatty acids may increase AD risk by reducing plasmalogen availability. Methods We measured four ethanolamine (PlsEtns) and closely related phosphatidylethanolamines (PtdEtns) from Disease Neuroimaging Initiative (ADNI; n = 1547 serum) University of Pennsylvania (UPenn; 112 plasma) cohorts, derived...
Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut-brain axis neurodegeneration. Bile acids (BA), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1,464 subjects including 370 cognitively...
Abstract Alzheimer’s disease (AD) is the most common cause of dementia. The mechanism development and progression not well understood, but increasing evidence suggests multifactorial etiology, with a number genetic, environmental, aging-related factors. There growing body that metabolic defects may contribute to this complex disease. To interrogate relationship between system level metabolites susceptibility progression, AD Metabolomics Consortium (ADMC) in partnership Neuroimaging...