Faculty

Rima Kaddurah-Daouk

Professor in Psychiatry and Behavioral Sciences

Psychiatry & Behavioral Sciences, Behavioral Medicine
School of Medicine

Professor in the Department of Medicine

Medicine, Cardiology
School of Medicine

Faculty Network Member of the Duke Institute for Brain Sciences

Duke Institute for Brain Sciences
Institutes and Provost's Academic Units
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3552, Blue Zone, Duke South, Durham, NC 27710

Box 3903 Med Ctr, Durham, NC 27710

(919) 684-2611 kaddu001@mc.duke.edu

Overall Research Goals:


My research interest over the past decade has focused on scaling up biochemical knowledge for gaining a deeper understanding of the molecular basis of neurodegenerative and neuropsychiatric disorders and finding ways to optimize their treatment. I have also made seminal contributions to the development of the metabolomics field and applications of metabolomics for the study of drug effects, establishing foundations for “Pharmacometabolomics”, a discipline that complements and informs pharmacogenomics and enables Precision Medicine initiatives. Over the next five years, I will continue to expand on these directions and applications of a systems biochemical approach, hoping to contribute in significant ways to President Obama’s Alzheimer’s Initiative as well as to Precision Medicine national and global initiatives. At the heart of my research is a deeper understanding of neuropsychiatric disease mechanisms, disease heterogeneity, and optimization of treatment for patients based on genotype, metabotype, microbiome activity and environmental influences and strategies for personalizing and optimizing treatment outcomes. 


Biographical History and Educational Background:


With training in chemistry and biochemistry at the American University of Beirut during my PhD work, training in molecular biology during post-graduate training at Johns Hopkins (worked with Nobel Laureate Hamilton Smith) and with subsequent training in genetics and molecular biology at Massachusetts General Hospital (MGH) and the Massachusetts Institute of Technology (MIT), I have gained a strong foundation in basic research. This broad training has enabled me to use integrated approaches and tools to solve problems in biology and to build foundations for a “systems biology” approach for the study of neuropsychiatric diseases and a “systems pharmacology” approach for the study of drug effects. During my work at MIT and while working closely with Professor Paul Schimmel, who played a seminal role in the evolution of the biotechnology industry, I developed a strong appreciation for applications of basic research and realized the importance of translation research and paths to develop new therapies based on novel findings. I have cofounded three biotechnology companies toward achieving this goal, the most recent being Metabolon, a biotechnology company that has played a central role in developments and applications of metabolomics in the medical field. I joined the Duke Department of Psychiatry and Behavioral Sciences in 2005 as an Adjunct Associate Professor while transitioning out of Metabolon, then in 2006 became a full-time Associate Professor focusing on a deeper understanding of the molecular basis of neuropsychiatric diseases, and devoted significant time to the development of the metabolomics field and its applications. While at Duke, I have played scientific leadership roles nationally and internationally, led large consortia that created new scientific disciplines, made major contributions toward defining novel mechanisms in neuropsychiatric diseases and raised close to 20 million dollars for research funding (mainly NIH with not-for-profit and for-profit funding) in areas of precision medicine.  


Academic Achievements and Scholarship:


Areas of research in which I have made significant contributions include:



The study of metabolic impairments in neuropsychiatric diseases including depression, schizophrenia and Alzheimer’s disease.
Metabolomics technologies and applications for the study of human disease and treatment outcomes; helped create a community of metabolomics researchers.
Established foundations for “Pharmacometabolomics”, a new field for the application of metabolomics for the study of drug effects and variation of response to treatment as enabling tools for precision medicine. Contributed to the rapidly growing field of “Quantitative and Systems Pharmacology” by linking the metabolome and genome and drug response.
Made several discoveries on the role of the gut microbiome in neuropsychiatric diseases and response to treatment.
Helped move basic research from bench to clinic with discoveries concerning creatine kinase and energy impairment in neurodegenerative diseases.

Below I exemplify from work that was done through large consortia and networks that I have built with NIH funding.


Metabolic failures in neuropsychiatric diseases:  Ground-breaking work was done in applying metabolomics and lipidomics tools for the study of neuropsychiatric diseases. More than twenty published papers have brought totally new insights about pathway and network changes in these disorders.


A. Studies in Schizophrenia - Using lipidomics technologies, we identified major changes in membrane structure and function that happen very early in the disease process. Lipid metabolism defects were noted both centrally and peripherally, suggesting that the disease is systemic and affects different organs. By using complimentary metabolomics platforms and focusing on neurotransmitters and related pathways, we provided new support to the idea that the different hypotheses of schizophrenia (dopamine, serotonin, glutamate) seem to be all part of one hypothesis due to interconnectedness within these pathways and have moved to evaluate failures within a metabolic network context. We provided the first lipidomics map for three atypical antipsychotic drugs and defined signatures that correlate with response to treatment.


B. Studies in Depression - Metabolomics studies in major depression revealed changes in mitochondrial beta oxidation, lipid metabolism and neurotransmission, with remission showing a unique metabolic state. For the first time, we mapped global changes related to the use of three antidepressants (selective serotonin reuptake inhibitors [SSRIs]) and defined pathways implicated in response and slow progressive metabolic changes that might explain delayed response to these medications. We defined metabolic changes correlated with response to placebo and compared that to response to SSRIs.  We generated new hypotheses regarding the mechanism of action for the rapid-acting drug ketamine. Such studies, if validated, can provide powerful tools for patient sub-classification and the streamlining of clinical trials, as well as insights for novel drug discovery.


C. Studies in Alzheimer’s Disease - Over the past four years, we have assembled an interdisciplinary team of experts in metabolomics, genetics, biochemistry, bioinformatics, biomarker discovery and clinical trials, and have begun to define perturbations in interlinked biochemical pathways across the trajectory of Alzheimer’s disease (AD). Using non-targeted lipidomics platforms, we defined changes in phosphatidyl cholines (PC), plasmalogens and the sphingolipidome. These changes suggest alterations in membrane structure and function in AD. Using targeted and non-targeted metabolomics platforms, we have identified defects in the methionine (MET)/one carbon metabolism pathway – this pathway regulates fundamental cellular methylation processes, including steps in phospholipid biosynthesis. It also generates homocysteine, the elevation of which has been linked to neurotoxicity, oxidative stress, DNA damage, and increased risk for both stroke and dementia. Perturbation in the interconnected neurotransmitter systems norepinephrine (NE) and tryptophan (TRP) and the linked purine (PUR) pathway were also identified, reflecting failures in neurotransmission and mitochondrial dysfunction. Constructed metabolic networks linked perturbations in NE and PUR with elevated tau, and changes in TRP and MET to amyloid-beta42. In partnership with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and with funding from the NIA, we established the Alzheimer’s Disease Metabolomics Consortium with the goal of creating a comprehensive metabolic database for ADNI linking metabolomics data to genomics and imaging data. This is in line with major recommendations and concepts we developed in the Alzheimer’s Summits of 2012 and 2015, and in response to President Obama initiative to prevent or treat AD by 2025. This consortium became part of Accelerating Medicines Partnership-Alzheimer's Disease (AMP-AD) program coordinated by FNIH for implementing the President mandate for accelerating treatments for AD.


Contributions to the emergence of a new field “Metabolomics”:  Vision creation: In the year 2000 before the term “metabolomics” was used in the United States, and through a series of patent applications, I put forward an early vision about how metabolomics could radically transform our current understanding, monitoring and management of human disease. Together with a team of scientists, we put forward concepts that metabolic signatures could (1) provide diagnostic, prognostic and surrogate markers for a disease state; (2) enable the sub-classification of disease; (3) provide biomarkers for drug response phenotypes (pharmacometabolomics); and (4) provide information about mechanisms of disease. We provided some of the earliest support for these concepts. Creation of Metabolomics leading Biotechnology Company: At the early stages and while funding for metabolomics was not available through the NIH, I co-founded Metabolon Inc., a biotechnology company to explore concepts of metabolomics and applications in the medical field. The company has made substantial contributions to the evolution of the metabolomics field and its applications to the study of human disease. Established the Metabolomics Society: I recognized the need for a platform that can bring together researchers interested in the concept of metabolomics. I cofounded the Metabolomics Society, an international non-profit organization with the mission of promoting the field of metabolomics. During my presidency and from a modest beginning, the society grew to over 500 members from 25 countries within the first four years. I organized national and international meetings and workshops, and brought together a team to establish the first version of minimal standards for the field. I also helped with the creation and positioning of “Metabolomics”, the official journal for the Metabolomics Society.


Established Foundations for Pharmacometabolomics - A sub-field of metabolomics that complements and informs pharmacogenomics and enables precision medicine. With funding from the NIGMS (including large stimulus funding), I established the “Pharmacometabolomics Research Network (PMRN) that includes over thirty scientists from different disciplines. The goal was to integrate metabolomics with pharmacology and pharmacogenetics in partnership with the Pharmacogenomics Research Network (PGRN) as steps to enable a Quantitative and Systems Pharmacology approach towards precision medicine. Eight years later, pharmacometabolomics is an established field that determines the so-called “metabotype” or metabolic state of an individual as affected by environmental, genetic and enteric microbiome influences to study drug responses and to understand treatment outcomes. It provides tools for mapping the global effects of drugs on metabolism and for identifying pathways and networks implicated in mechanisms of action and mechanisms of variation in response to treatment. With over 30 publications, we lead this area of research; provided totally new insights about the molecular basis for on- and off-target effects of major classes of therapies including SSRIs, statin, antiplatelet and antihypertensive therapies. We also provided insights about treatment outcomes,  ethnic and gender basis for variation of response and exemplified how metabolomics is an enabling tool for precision medicine.


Established support for the role of the gut microbiome in neuropsychiatric diseases and response to statins: Metabolic signatures for several neuropsychiatric diseases suggested changes related to gut microbiome host co-metabolism. Variation of response to statins was shown to involve, in part, gut microbiome activity and function.


Contributions that led to the Development of Creatine as a Potential Combination Therapy for Treating Neurodegenerative Diseases. Earlier in my career, I led research that resulted in unraveling a new role for the Creatine Kinase system in neuronal cell death. Along with Dr. Flint Beal, then at Harvard, we revealed neuroprotective properties of creatine analogs in animal models of Amyotrophic Lateral Sclerosis and Parkinson’s disease. I led creatine development from the bench to the clinic. Subsequent large investments made by the NIH to clinical teams resulted in testing the natural compound creatine in phase II and III studies for the treatment of Parkinson’s and Huntington’s diseases.  


Education & Training

B.S. 1978

American University of Beirut (Lebannon)

Ph.D. 1983

American University of Beirut (Lebannon)

Grants

Alzheimer's Gut Microbiome Project

National Institutes of Health

Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-AD

National Institutes of Health

Gut Liver Brain Biochemical Axis in Alzheimer's Disease

National Institutes of Health

Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to Treatment

National Institutes of Health

Metabolic Network Analysis of Biochemical Trajectories in Alzheimer's Disease

National Institutes of Health

GOLDILOKs: Genomic- and Ontogeny-Linked Dose Individualization and cLinical Optimization for Kids

Interdisciplinary Research to Understand the Interplay of Diabetes, Cerebrovascular disease and Alzheimers disease

Metabolomic pathways in Food Allergy

Integrative translational discovery of vascular risk factors in aging and dementia

Mayo Clinic

Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type Dementias

National Institutes of Health

Metabolomic Signatures Predictive of Outcomes to Treatments for Major Depression

National Institutes of Health

Inherited Variations in Drug Metabolizing Enzymes

Mayo Clinic

Ex vivo metabolomic profiling of statin-induced myopathy

American Heart Association

AMP AD Project B Biomarker Pilot Study: An integrated biomarker discovery pilot study (Broad/Rush-Emory-Duke)

The IU/JAX Alzheimer's Disease Precision Models Center

Indiana University

Metabolic Networks and Pathways in Alzheimer's Disease

National Institutes of Health

Metabolomic Platforms Testing for Neurosteroid Effects

National Institutes of Health

Metabolic Signature for Ketamine Exposure

Alzheimer's Disease Neuroimaging Initiative

INDICIES: INDIviualised drug therapy based on pharmacogenomics: focus on carboxylesterase 1 (CES1)

The Metabolomics Data Center and Workbench (MDCW)

Metabolic Signature for Ketamine Exposure and Ketamine Response

National Institutes of Health

Metabolomic Study of Reproductive Steriods

National Institutes of Health

Metabolomic Signatures and Biomarkers for Schizophrenia

National Institutes of Health

Metabolomics 2012

National Institutes of Health

Metabolomics Network for Drug Response Phenotype

National Institutes of Health

Metabolomics Network for Drug Response Phenotype

National Institutes of Health

Metabolic Signatures for Alzheimer's Disease

National Institutes of Health

Pharmacometabolomics Research Network

National Institutes of Health

Administrative Supplement to Metabolic Signatures for Alzheimer's Disease

National Institutes of Health

Tryptophan Metabolism, Genes, and Major Depression

National Institutes of Health

Metabolomic Profile of Samples from Patients with Mood and Anxiety Disorders

National Institute of Mental Health
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Publications

Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes

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Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.

PMID 31674729
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Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology.

PMID 31517024
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Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma.

PMID 31669435
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Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts.

PMID 31624257
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Biobanking for Metabolomics and Lipidomics in Precision Medicine.

PMID 31088785
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Systematic Error Removal Using Random Forest for Normalizing Large-Scale Untargeted Lipidomics Data.

PMID 30758187
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Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.

PMID 30337152
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Metabolic dysfunctions in the kynurenine pathway, noradrenergic and purine metabolism in schizophrenia and bipolar disorders

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Expert insights: The potential role of the gut microbiome-bile acid-brain axis in the development and progression of Alzheimer's disease and hepatic encephalopathy

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Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

PMID 30337151
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Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment.

PMID 31572108
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Generation and quality control of lipidomics data for the alzheimer's disease neuroimaging initiative cohort.

PMID 30457571
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Mapping depression rating scale phenotypes onto research domain criteria (RDoC) to inform biological research in mood disorders.

PMID 29807322
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Augmentation of Physician Assessments with Multi-Omics Enhances Predictability of Drug Response: A Case Study of Major Depressive Disorder.

PMID 30467458
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Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate.

PMID 30169917
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Ketamine and ketamine metabolites as novel estrogen receptor ligands: Induction of cytochrome P450 and AMPA glutamate receptor gene expression.

PMID 29621538
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The inhibition of the kynurenine pathway prevents behavioral disturbances and oxidative stress in the brain of adult rats subjected to an animal model of schizophrenia.

PMID 29030243
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Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics.

PMID 29317604
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Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

PMID 29370177
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Sphingolipid Metabolic Pathway Impacts Thiazide Diuretics Blood Pressure Response: Insights From Genomics, Metabolomics, and Lipidomics.

PMID 29288159
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Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.

PMID 29039849
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Data-driven longitudinal modeling and prediction of symptom dynamics in major depressive disorder: Integrating factor graphs and learning methods

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Metabolic network failures in Alzheimer's disease: A biochemical road map.

PMID 28341160
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The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback.

PMID 28786978
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Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life.

PMID 28433652
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Nomenclature for alleles of the human carboxylesterase 1 gene.

PMID 27831961
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Pharmacometabolomic signature links simvastatin therapy and insulin resistance

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Pharmacometabolomic signature links simvastatin therapy and insulin resistance.

PMID 29732238
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TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics.

PMID 26903268
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Metabolomics enables precision medicine: “A White Paper, Community Perspective”

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Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.

PMID 27648916
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A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

PMID 27381900
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Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach.

PMID 28217400
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Pharmacometabolomics informs pharmacogenomics

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Pharmacometabolomic assessment of metformin in non-diabetic, African Americans

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Investigating the impact of missense mutations in hCES1 by in silico structure-based approaches

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A METFORMIN METABOLOMIC EXPRESSION PROFILE STUDY UTILIZING AN ELECTRONIC HEALTH RECORD (EHR)-LINKED BIOREPOSITORY AND INTEGRATIVE MOLECULAR EPIDEMIOLOGY APPROACHES

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Genetic Influences on Plasma Homocysteine Levels in African Americans and Yoruba Nigerians.

PMID 26519441
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Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

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Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes.

PMID 26783503
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Oxylipid Profile of Low-Dose Aspirin Exposure: A Pharmacometabolomics Study.

PMID 26504148
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Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans.

PMID 26194313
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Metabolomic Signatures for Drug Response Phenotypes: Pharmacometabolomics Enables Precision Medicine.

PMID 25871646
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Synthetic cannabimimetic agents metabolized by carboxylesterases.

PMID 25346527
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Associations between central nervous system serotonin, fasting glucose, and hostility in African American females.

PMID 24806470
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Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review.

PMID 26109927
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Module-based association analysis for omics data with network structure.

PMID 25822417
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Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics.

PMID 25896426
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Quality assurance of metabolomics.

PMID 26536290
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Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability.

PMID 25029353
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Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

PMID 24627569
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Pharmacometabolomics: implications for clinical pharmacology and systems pharmacology.

PMID 24193171
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Integration of pharmacometabolomic and pharmacogenomic approaches reveals novel insights into antiplatelet therapy.

PMID 23892404
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Pharmacometabolomics of statin response.

PMID 23945822
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Purine pathway implicated in mechanism of resistance to aspirin therapy: pharmacometabolomics-informed pharmacogenomics.

PMID 23839601
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Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

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Comparing metabolomic and pathologic biomarkers alone and in combination for discriminating Alzheimer's disease from normal cognitive aging.

PMID 24252434
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Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis

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Correction: Enteric microbiome metabolites correlate with response to simvastatin treatment (PLoS ONE)

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Alterations in metabolic pathways and networks in Alzheimer's disease.

PMID 23571809
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Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

PMID 23340506
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Pharmacometabolomics reveals racial differences in response to atenolol treatment.

PMID 23536766
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Pharmacometabolomic signature of ataxia SCA1 mouse model and lithium effects.

PMID 23936457
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Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway.

PMID 23874572
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Purine pathway implicated in mechanism of resistance to aspirin therapy: Pharmacometabolomics-informed pharmacogenomics

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Enantioselective determination of methylphenidate and ritalinic acid in whole blood from forensic cases using automated solid-phase extraction and liquid chromatography-tandem mass spectrometry.

PMID 22833645
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Impaired plasmalogens in patients with schizophrenia.

PMID 22513041
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Interest in metabolomics continues to grow within US National Institutes of Health (NIH)

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Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.

PMID 22322242
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Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart failure and major depressive disorder.

PMID 22042636
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Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile.

PMID 22993692
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Associations between purine metabolites and clinical symptoms in schizophrenia.

PMID 22916123
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Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment.

PMID 22808006
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3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia.

PMID 21275080
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Associations between Purine Metabolites and Clinical Symptoms in Schizophrenia

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Metabolomic changes in autopsy-confirmed Alzheimer's disease.

PMID 21075060
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GLYCINE AND A GLYCINE DEHYDROGENASE (GLDC) SNP AS SSRI RESPONSE BIOMARKERS IN DEPRESSION: PHARMACOMETABOLOMICS-INFORMED PHARMACOGENOMICS

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GLYCINE AND A GLYCINE DEHYDROGENASE (GLDC) SNP AS SSRI RESPONSE BIOMARKERS IN DEPRESSION: PHARMACOMETABOLOMICS-INFORMED PHARMACOGENOMICS

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Glycine and a glycine dehydrogenase (GLDC) SNP as citalopram/escitalopram response biomarkers in depression: pharmacometabolomics-informed pharmacogenomics.

PMID 21107318
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Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.

PMID 21779331
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Enteric microbiome metabolites correlate with response to simvastatin treatment.

PMID 22022402
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Pretreatment metabotype as a predictor of response to sertraline or placebo in depressed outpatients: a proof of concept.

PMID 22162828
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Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

PMID 19401681
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Stable isotope-resolved metabolomic analysis of lithium effects on glial-neuronal metabolism and interactions.

PMID 20631920
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Metabolomic differences in heart failure patients with and without major depression.

PMID 20101071
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Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.

PMID 20445760
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Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

PMID 20209081
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Metabolomics: A global biochemical approach to the discovery of biomarkers for psychiatric disorders

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Opioid use affects antioxidant activity and purine metabolism: preliminary results.

PMID 19760630
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Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study.

PMID 19649617
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Metabolomic Mapping of Atypical Effects in Schizophrenia

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Metabolomics tools for identifying biomarkers for neuropsychiatric diseases.

PMID 19303440
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Abnormalities in Inflammatory Lipid Levels in First Episode Schizophrenic Patients are Modulated by Risperidone

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Homeostatic Imbalance of Purine Catabolism in First-Episode Neuroleptic-Naive Patients with Schizophrenia

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Metabolomics: A Global Biochemical Approach to the Study of Neuropsychiatric Disorders

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3-HYDROXYKYNURENINE AND COGNITIVE IMPAIRMENT IN FIRST-EPISODE NEUROLEPTIC-NAIVE PATIENTS WITH SCHIZOPHRENIA

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Metabolomics: a global biochemical approach to the study of central nervous system diseases.

PMID 18843269
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Metabolomic mapping of schizophrenic patients treated with atypical antipsychotics discloses drug-specific differences in global lipid changes

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Metabolomics and lipidomics of neuropsychiatric disorders: Emerging data

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Discriminative tryptophan pathway in first-episode neuroleptic-naive patients with schizophrenia

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Metabolomics: a global biochemical approach to drug response and disease.

PMID 18184107
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Inflammatory changes in schizophrenia with antipsychotic treatment

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Metabolomics: Concepts and potential neuroscience applications

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Metabolomic mapping of atypical antipsychotic effects in schizophrenia.

PMID 17440431
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The metabolomics standards initiative (MSI)

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ANYL 288-Metabolomics for mapping disease signatures and drug response phenotypes

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The metabolomics standards initiative.

PMID 17687353
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A preliminary metabolomic analysis of older adults with and without depression.

PMID 17048218
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Metabolomic mapping of schizophrenia and atypical antipsychotic effects

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Metabolomics in the study of aging and caloric restriction

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High-performance liquid chromatography separations coupled with coulometric electrode array detectors: a unique approach to metabolomics.

PMID 17035686
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Metabolomics in the study of aging and caloric restriction.

PMID 17634593
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A preliminary metabolomic analysis of older adults with and without depression

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Metabolic profiling of patients with schizophrenia.

PMID 16933969
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Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results.

PMID 16772263
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Biomarkers for amyotrophic lateral sclerosis.

PMID 16706741
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Identification of metabolic and protein biomarkers for amyotrophic lateral sclerosis

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Establishing reporting standards for metabolomic and metabonomic studies: a call for participation.

PMID 16901221
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Metabolic profiling of patients with schizophrenia.

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Metabolomics: A new approach towards identifying biomarkers and therapeutic targets in CNS disorders

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Metabolomic analysis and signatures in motor neuron disease.

PMID 18820733
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Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation.

PMID 11299300
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Creatine and creatinine metabolism.

PMID 10893433
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Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.

PMID 10844007
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Neuroprotective effects of creatine administration against NMDA and malonate toxicity.

PMID 10727643
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Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent

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The neuroprotective properties of creatine in animal models of neurodegenerative diseases

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Creatine and cyclocreatine attenuate MPTP neurotoxicity.

PMID 10222117
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Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.

PMID 10086395
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Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase.

PMID 9724093
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Antitumor activity of creatine analogs produced by alterations in pancreatic hormones and glucose metabolism.

PMID 9627806
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Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease.

PMID 9412496
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Synthesis and creatine kinase inhibitory activity of nonhydrolyzable analogs of phosphocreatine

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Specific targeting of tumor cells by the creatine analog cyclocreatine

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Depletion of energy reserve via the creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters.

PMID 8732503
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The synthetic phosphagen cyclocreatine phosphate inhibits the growth of a broad spectrum of solid tumors.

PMID 8615639
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Creatine and phosphocreatine analogs: anticancer activity and enzymatic analysis.

PMID 8823808
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Antiproliferative effects of cyclocreatine on human prostatic carcinoma cells.

PMID 7654018
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Microtubule stabilization and potentiation of taxol activity by the creatine analog cyclocreatine.

PMID 7670140
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Enhancement of cardiac function by cyclocreatine in models of cardiopulmonary bypass.

PMID 7563103
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Erratum: Microtubule stabilization and potentiation activity by the creatine analog cyclocreatine (Anti-Cancer Drugs (1995) 6 (419-426))

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Cyclocreatine in cancer chemotherapy.

PMID 7850923
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Cell cycle studies of cyclocreatine, a new anticancer agent.

PMID 7923134
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Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells.

PMID 8145276
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Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses.

PMID 8042860
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Enhancement of the recovery of rat hearts after prolonged cold storage by cyclocreatine phosphate.

PMID 8154024
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Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.

PMID 8319226
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Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a.

PMID 2138706
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Isolation of a functional human gene for brain creatine kinase.

PMID 2828370
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Activation and repression of mammalian gene expression by the c-myc protein.

PMID 3678827
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Purification of the HhaII restriction endonuclease from an overproducer Escherichia coli clone.

PMID 2999111
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Catalytic properties of the HhaII restriction endonuclease.

PMID 2999112
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