https://www.c4p.info/static/js/main.7ee55023.js

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263pulation of blood by not separating different cell types, so good RNA preservation. Ease of deployment in the field for population studies."},{question:"Why not immortalized lymphoblastoid cell lines?",answer:"Because they can be riddled with Epstein-Barr virus (EBV) induced artifacts, cell culture passaging artifacts, and have no direct correlation with measured clinical state."},{question:"Does it matter from which cell type the biomarkers come? What about CBC variations?",answer:"On the front end (discovery), it does not matter from which blood cells the biomarkers come, as we are not interested in blood cell biology, we just want to find peripheral markers. On the back end, for clinical implementation, after a biomarker is discovered and validated, larger population studies need to be conducted to find normative levels for laboratory testing. At that point, understanding which cell types the biomarkers come from should be done, as variations in CBC (infections, immune disorders) could influence biomarker levels."},{question:"Why would changes in blood gene expression reflect changes in the brain?",answer:"Likely due to conserved signal transduction modules in different cell types, similar promoter regions, and common exposure to environmental factors like stress and medications. However, the signal is buried in noise, so you need a good design and methodology for extracting it."},{question:"Why are we successful with relatively small cohorts?",answer:(0,_i.jsxs)(Kr,{children:[(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Phenotype:"})," We prefer to study discrete quantitative phenotypes, not broad diagnostic categories. We focus on state markers, correlated with phenes measured at the time of blood draw, not trait markers."]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Cohorts:"})," Separated by gender and ethnicity for homogeneity and noise reduction."]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Gene expression:"})," Gene expression integrates the effects of thousands of SNPs and environmental factors."]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Study design:"}),(0,_i.jsxs)(Kr,{children:[(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Intra-subject design:"})," Best for factoring out genetic variability. Requires n~101 for gene expression studies."]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Case-case design:"})," Factors out some disease-related variability. Requires n~102 for gene expression studies."]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Case-control design:"})," Least effective due to population heterogeneity and noise. Requires n~103 for gene expression studies."]})]})]}),(0,_i.jsxs)(qr,{children:[(0,_i.jsx)("strong",{children:"Convergent Functional Genomics (CFG):"})," A Bayesian method to identify and prioritize disease-related genes from differentially expressed genes in the blood. CFG ensures biomarkers are fit-to-disease rather than fit-to-cohort, allowing reproducibility in independent cohorts."]})]})}];return(0,_i.jsxs)(Hr,{children:[(0,_i.jsx)(Ur,{children:'Biomarker Discovery Efforts - The "Secrets" of Our Success FAQ'}),e.map(((e,t)=>(0,_i.jsxs)("div",{children:[(0,_i.jsx)(Wr,{children:e.question}),(0,_i.jsx)(Jr,{children:e.answer})]},t)))]})},Qr=n.p+"static/media/CFGimg.da390f15490009f0fff5.jpg",Xr=Ei.div`
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298ipolar disorder and schizophrenia (Le-Niculescu et al, 2007), which has been confirmed by more recent independent studies. Based on our work and that of others in the field, we believe that the contextual cumulative combinatorics of common (normal) genetic variants may underlie the vulnerability or resilience to disease, in lieu of or in addition to rare (abnormal) mutations."}),(0,_i.jsx)(na,{children:"We have proposed a combinatorial modular Lego game-like model for psychiatric disorders. It is likely that panels of markers (SNPs, biomarkers) rather than single markers will emerge as useful profiling tools for personalized/precision medicine approaches."})]}),(0,_i.jsx)("img",{src:Qr,alt:"Lab Mission Visual"}),(0,_i.jsxs)(ea,{children:[(0,_i.jsx)(na,{children:"This Bayesian strategy for cross-validating findings extracts meaning from large datasets by prioritizing candidate genes, pathways, and mechanisms; which are then targeted by subsequent hypothesis-driven research. Top candidate genes, for which there are multiple independent lines of evidence, are less likely to be false positives. The network of lines of evidence for each gene is resilient, even if one or another of the nodes (lines of evidence) is less than optimal."}),(0,_i.jsx)(na,{children:"In the end, the results speak for themselves in terms of the ability of our Convergent Functional Genomics approach to extract signal and prioritize findings, similar to a Google PageRank algorithm, from large and potentially noisy datasets. The CFG approach has been successfully applied to bipolar disorder, schizophrenia, anxiety, alcoholism, and blood biomarker discovery."})]}),(0,_i.jsxs)(ea,{children:[(0,_i.jsx)(ta,{children:"Biomarkers"}),(0,_i.jsx)(na,{children:"Biomarkers: concordant gene expression in brain and peripheral tissues such as blood, due to inherited genetic factors (e.g., promoter regions, signal transduction modules) or external factors (medications, stress and other environmental effects)."})]})]})},ra=n.p+"static/media/AnimalIMG1.3043b9d5098c0b7fc60f.jpg",aa=n.p+"static/media/AnimalIMG2.a724ff75097ab3370b64.jpg",oa=n.p+"static/media/AnimalIMG3.78e29c4dfd5a83d18478.jpg",sa=Ei.div`
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515,{title:"Dissecting Suicidality Using a Combined Genomic and Clinical Approach",authors:"Niculescu AB, Le-Niculescu H",journal:"Neuropsychopharmacology. 2017 Jan;42(1):360",doi:"10.1038/npp.2016.228",pmid:"27909331",link:"/assets/pdfs/PDF14.pdf"},{title:"Mood, Stress and Longevity: Convergence on ANK3",authors:"Rangaraju S, Levey DF, Nho N, Jain N, Andrews KD, Le-Niculescu H, Salomon DR, Saykin AJ, Petrascheck M, Niculescu AB",journal:"Molecular Psychiatry. 2016 Aug;21(8):1037-1049",doi:"10.1038/mp.2016.65",pmid:"27217151",link:"/assets/pdfs/PDF15.pdf"},{title:"Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment",authors:"Levey DF, Niculescu EM, Le-Niculescu H, Dainton HD, Phalen PL, Ladd TB, Weber H, Belanger E, Graham DL, Khan FN, Vanipenta NP, Stage EC, Ballew A, Yard M, Gelbart T, Shekhar A, Schork NJ, Kurian SM, Sandusky GE, Salomon DR, Niculescu AB",journal:"Molecular Psychiatry. 2016 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Ballew A, Yard M, Gelbart T, Shekhar A, Schork NJ, Kurian SM, Sandusky GE, Salomon DR",journal:"Molecular Psychiatry. 2015 Sep;20(11):1266-1285",doi:"10.1038/mp.2015.112",pmid:"26283638",link:"/assets/pdfs/PDF19.pdf"},{title:"Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non-cell-autonomous stress response",authors:"Rangaraju S, Solis GM, Andersson SI, Gomez-Amaro RL, Kardakaris R, Broaddus CD, Niculescu AB, Petrascheck M",journal:"Aging Cell. 2015 Dec;14(6):971-981",doi:"10.1111/acel.12379",pmid:"26255886",link:"/assets/pdfs/PDF20.pdf"},{title:"Characteristics of Bipolar I patients grouped by externalizing disorders",authors:"Swaminathan S, Koller DL, Foroud T, Edenberg HJ, Xuei X, Niculescu AB, Nurnberger JI Jr",journal:"J Affect Disord. 2015 Jun 1;178:206-214",doi:"10.1016/j.jad.2015.03.011",pmid:"25827505",link:"/assets/pdfs/PDF21.pdf"},{title:"Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults",authors:"Nho K, Ramanan VK, Horgusluoglu E, Kim S, Inlow MH, Risacher SL, McDonald BC, Farlow MR, Foroud TM, Gao S, Callahan CM, Hendrie HC, Niculescu AB, Saykin AJ",journal:"J Alzheimers Dis. 2015;45(4):1197-1206",doi:"10.3233/JAD-148009",pmid:"25690665",link:"/assets/pdfs/PDF22.pdf"},{title:"Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions",authors:"Niculescu AB, Levey DF, Le-Niculescu H, Niculescu E, Kurian SM, Salomon DR",journal:"Molecular Psychiatry. 2015 Mar;20(3):286-288",doi:"10.1038/mp.2014.180",pmid:"25582618",link:"/assets/pdfs/PDF23.pdf"},{title:"Genetic Risk Prediction and Neurobiological Understanding of Alcoholism",authors:"Levey DF, Le-Niculescu H, Frank J, Ayalew M, Jain N, Kirlin B, Learman R, Winiger E, Rodd ZA, Shekhar A, Schork NJ, Kiefe F, Wodarz N, M\xfcller-Myhsok B, Dahmer N, GESGA Consortium, N\xf6then M, Sherva R, Farrer L, Smith AH, Kranzler H, Rietschel M, Gelernter J, Niculescu AB",journal:"Translational Psychiatry. 2014 May 20;4:e391",doi:"10.1038/tp.2014.29",pmid:"24844177",link:"/assets/pdfs/PDF24.pdf"},{title:"Convergent functional genomics of stem cell-derived cells",authors:"Niculescu AB",journal:"Translational Psychiatry. 2013 Sep 10;3:e305",doi:"10.1038/tp.2013.78",pmid:"24022510",link:"/assets/pdfs/PDF25.pdf"},{title:"Discovery and validation of blood biomarkers for suicidality",authors:"Le-Niculescu H, Levey D, Ayalew M, Palmer L, Gavrin LM, Jain N, Winiger E, Bhosrekar S, Shankar G, Radel M, Bellanger E, Duckworth H, Olesek K, Vergo J, Schweitzer R, Yard M, Ballew A, Shekhar A, Sandusky GE, Schork NJ, Kurian SM, Salomon DR, Niculescu AB",journal:"Molecular Psychiatry. 2013 Dec;18(12):1249-1264",doi:"10.1038/mp.2013.95",pmid:"23958961",link:"/assets/pdfs/PDF26.pdf"},{title:"Convergent Functional Genomics of Psychiatric Disorders",authors:"Niculescu AB",journal:"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2013 Oct;162B(7):587-594",doi:"10.1002/ajmg.b.32163",pmid:"23728881",link:"/assets/pdfs/PDF27.pdf"},{title:"Convergent Functional Genomics of Schizophrenia: From Comprehensive Understanding to Genetic Risk Prediction",authors:"Ayalew M, Le-Niculescu H, Levey D, Jain N, Changala B, Patel SD, Winiger E, Breier A, Shekhar A, Amdur R, Koller D, Nurnberger JI, Corvin A, Geyer M, Tsuang MT, Salomon DR, Schork NJ, Fanous A, O\u2019Donovan M, Niculescu AB",journal:"Molecular Psychiatry. 2012 Sep;17(9):887-905",doi:"10.1038/mp.2012.37",pmid:"22584867",link:"/assets/pdfs/PDF28.pdf"},{title:"Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms",authors:"Le-Niculescu H, Balaraman Y, Patel SD, Ayalew M, Gupta J, Kuczenski R, Shekhar A, Schork N, Geyer MA, Niculescu AB",journal:"Translational Psychiatry. 2011 May 24;1:e9",doi:"10.1038/tp.2011.6",pmid:"22832404",link:"/assets/pdfs/PDF29.pdf"},{title:"Convergent Functional Genomic Studies of Omega-3 Fatty Acids 

515in Stress Reactivity, Bipolar Disorder and Alcoholism",authors:"Le-Niculescu H, Case NJ, Hulvershorn L, Patel SD, Bowker D, Gupta J, Bell R, Edenberg HJ, Tsuang MT, Kuczenski R, Geyer MA, Rodd Z, Niculescu AB",journal:"Translational Psychiatry. 2011 Apr 26;1:e4",doi:"10.1038/tp.2011.3",pmid:"22832392",link:"/assets/pdfs/PDF30.pdf"},{title:"Identification of blood biomarkers for psychosis using convergent functional genomics",authors:"Kurian SM, Le-Niculescu H, Patel SD, Bertram D, Davis J, Dike C, Yehyawi N, Lysaker P, Dustin J, Caligiuri M, Lohr J, Lahiri DK, Nurnberger JI Jr, Faraone SV, Geyer MA, Tsuang MT, Schork NJ, Salomon DR, Niculescu AB",journal:"Molecular Psychiatry. 2011 Jan;16(1):37-58",doi:"10.1038/mp.2009.117",pmid:"19935739",link:"/assets/pdfs/PDF31.pdf"},{title:"Convergent Integration of Animal Model and Human Studies of Bipolar Disorder (manic-depressive illness)",authors:"Le-Niculescu H, Patel SD, Niculescu AB",journal:"Current Opinion in Pharmacology. 2010 Dec;10(5):594-600",doi:"10.1016/j.coph.2010.06.011",pmid:"20817606",link:"/assets/pdfs/PDF32.pdf"},{title:"Coming to Grips With Complex Disorders: Genetic Risk Prediction in Bipolar Disorder Using Panels of Genes Identified Through Convergent Functional Genomics",authors:"Patel SD, Le-Niculescu H, Koller DL, Green SD, Lahiri DK, McMahon F, Nurnberger JI, Niculescu AB",journal:"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2010 Jun 5;153B(4):850-877",doi:"10.1002/ajmg.b.31052",pmid:"20468069",link:"/assets/pdfs/PDF33.pdf"},{title:"The P-Value Illusion: How to Improve (Psychiatric) Genetic Studies",authors:"Niculescu AB, Le-Niculescu H",journal:"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2010 Jun 5;153B(4):847-849",doi:"10.1002/ajmg.b.31053",pmid:"20301110",link:"/assets/pdfs/PDF34.pdf"},{title:"Toward Early, Personalized, Rational Polypharmacy In Psychiatry: A Tri-Dimensional Approach",authors:"Niculescu AB, Hulvershorn L",journal:"Psychopharm Review. 2010;45(2):9-16",link:"/assets/pdfs/PDF35.pdf"},{title:"Convergent Functional Genomics: What We Have Learned and Can Learn About Genes, Pathways, and Mechanisms",authors:"Niculescu AB, Le-Niculescu H",journal:"Neuropsychopharmacology. 2010 Jan;35(1):355-356",doi:"10.1038/npp.2009.128",pmid:"20010721",link:"/assets/pdfs/PDF36.pdf"},{title:"Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics",authors:"Caligiuri MP, Teulings HL, Dean CE, Niculescu AB, Lohr JB",journal:"Psychiatry Research. 2010 May 15;177(1-2):77-83",doi:"10.1016/j.psychres.2009.02.001",pmid:"20381875",link:"/assets/pdfs/PDF37.pdf"},{title:"Evidence for genetic association of RORB with bipolar disorder",authors:"McGrath CL, Glatt SJ, Sklar P, Le-Niculescu H, Kuczenski R, Doyle AE, Biederman J, Mick E, Faraone SV, Niculescu AB, Tsuang MT",journal:"BMC Psychiatry. 2009 Nov 12;9:70",doi:"10.1186/1471-244X-9-70",pmid:"19909500",link:"/assets/pdfs/PDF38.pdf"},{title:"Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone",authors:"Caligiuri MP, Teulings HL, Dean CE, Niculescu AB, Lohr J",journal:"Human Movement Science. 2009 Oct;28(5):633-642",doi:"10.1016/j.humov.2009.08.001",pmid:"19692133",link:"/assets/pdfs/PDF39.pdf"},{title:"Mindscape: A convergent perspective on life, mind, consciousness and happiness",authors:"Niculescu AB, Schork NJ, Salomon DR",journal:"Journal of Affective Disorders. 2010 Jun;123(1-3):1-8",doi:"10.1016/j.jad.2009.10.008",pmid:"19595463",link:"/assets/pdfs/PDF40.pdf"},{title:"Convergent Functional Genomics of Genome-Wide Association Data for Bipolar Disorder: Comprehensive Identification of Candidate Genes, Pathways and Mechanisms",authors:"Le-Niculescu H, Patel SD, Bhat M, Kuczenski R, Faraone SV, Tsuang MT, McMahon FJ, Schork NJ, Nurnberger JI Jr, Niculescu AB",journal:"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2009 Mar 5;150B(2):155-181",doi:"10.1002/ajmg.b.30887",pmid:"19025758",link:"/assets/pdfs/PDF41.pdf"},{title:"Evidence of association between brain-derived neurotrophic factor (BDNF) gene and bipolar disorder",authors:"Liu L, Foroud R, Xuei X, Berrettini W, Byerley W, Coryell W, El-Mallakh R, Gershon E, Kelsoe J, Lawson W, MacKinnon D, McInnis M, McMahon F, Murphy D, Rice J, Scheftner W, Niculescu AB, Meyer ET, Edenberg HJ, Nurnberger JI Jr",journal:"Psychiatric Genetics. 2008 Dec;18(6):267-274",doi:"10.1097/YPG.0b013e328306a465",pmid:"19018231",link:"/assets/pdfs/PDF42.pdf"},{title:"Phenomic, convergent functional genomic and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism",authors:"Le-Niculescu H, McFarland MJ, Ogden CA, Balaraman Y, Patel S, Tan J, Rodd ZA, Paulus M, Geyer M, Edenberg HJ, Glatt SJ, Faraone SV, Nurnberger JI Jr, Kuczenski R, 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Genome Technology (2012)",link:"http://www.neurophenomics.info/GTFeb2012_QA.pdf"},{text:"Teaming up for biomarker future - EMBO Reports (2011)",link:"http://www.neurophenomics.info/Rinaldi_Biomarkers_EMBO%20rep%202011.pdf"},{text:"Omega-3 Fatty Acids and Psychiatric Disorders (2011)",link:"http://www.upi.com/Health_News/2011/05/26/Omega-3-may-help-treat-bipolar-disorder/UPI-50191306468299/"},{text:"Psychology Today June 2011",link:"http://www.neurophenomics.info/Psychology%20Today%20June%202011.pdf"},{text:"Dr. Niculescu featured in Indiana University's 2010 Annual Report on Research and Creative Activities.",link:"http://www.indiana.edu/~vpr/communications.shtml"},{text:"NIH Directors' New Innovator Award (2010)",link:"http://communications.medicine.iu.edu/newsroom/stories/2010/iu-psychiatrist-alexander-niculescu-awarded-prestigious-nih-gran/"},{text:"DNA Testing for Bipolar Disorder (2010)",link:"http://psychcentral.com/news/2010/04/14/test-for-genetic-risk-of-bipolar/12823.html"},{text:"Identifying Blood Biomarkers for Hallucinations and Delusions (2009)",link:"http://latimesblogs.latimes.com/booster_shots/2009/11/mental-illness-biomarkers.html"}]},{title:"Faulty Body Clock May Make Kids Bipolar (2009)",items:[{text:"Scientific American Mind",link:"http://www.nature.com/scientificamericanmind/journal/v21/n2/full/scientificamericanmind0510-13a.html"},{text:"ABC News",link:"http://abcnews.go.com/Health/Healthday/bipolar-disorder-tied-body-clock/story?id=9191876"},{text:"Telegraph.co.uk",link:"http://www.telegraph.co.uk/health/healthnews/6544910/Sleep-problems-could-trigger-manic-depression-in-children.html"},{text:"Science Daily",link:"http://www.sciencedaily.com/releases/2009/11/091111200213.htm"},{text:"U.S. News and World Report",link:"http://health.usnews.com/articles/health/healthday/2009/11/27/bipolar-disorder-may-be-tied-to-body-clock.html"},{text:"San Francisco Examiner",link:"http://www.examiner.com/x-10560-Special-Needs-Kids-Examiner~y2009m11d29-Gene-linked-to-susceptibility-of-symptoms-for-pediatric-bipolar-disorder"}]},{title:"Towards Improving Diagnosis in Psychiatry (2009)",items:[{text:"Diagnosis Weapons",link:"http://ivanhoe.com/viewers/watch_video.cfm?vid=RX1563&title=Diagnosis%20Weapons"},{text:"The Future of Testing for Bipolar Disorder - Featured on Bipolar TV",link:"http://www.webmd.com/bipolar-disorder/bipolar-tv/"}]},{title:"First Comprehensive Map Of Genes Likely To Be Involved In Bipolar Disorder (2008)",items:[{text:"NARSAD",link:"http://www.narsad.org/news/press/rg_2008/res2008-12-08b.html"},{text:"UPI ",link:"http://www.upi.com/Science_News/2008/11/22/Biopolar_genes_identified/UPI-70631227332748/"},{text:"Science Daily",link:"http://www.sciencedaily.com/releases/2008/11/081121180438.htm"}]},{title:"Identifying Blood Biomarkers for Mood Disorders (2008)",items:[{text:"Faculty of 1000 Biology: Major Advances, Expert Opinion",link:"http://www.f1000biology.com/article/id/1103999"},{text:"NARSAD",link:"http://www.narsad.org/news/press/rg_2008/res2008-03-05.html"},{text:"10 Leading Discoveries by NARSAD-Funded Scientists in 2008",link:"http://www.narsad.org/news/press/rg_2008/res2008-12-23b.html"},{text:"MSNBC",link:"http://www.msnbc.msn.com/id/23337532/"},{text:"New Scientist",link:"http://www.newscientist.com/article/mg19726454.700-simple-blood-test-could-predict-your-mood.html"},{text:"Dagens Nyheter: Sweden's largest morning paper",link:"http://www.dn.se/DNet/jsp/polopoly.jsp?d=597&a=746438"},{text:"BBC",link:"http://news.bbc.co.uk/2/hi/health/7262424.stm"},{text:"WebMD",link:"http://www.webmd.com/bipolar-disorder/news/20080225/a-blood-test-for-mood-disorders"},{text:"Scientific American",link:"http://www.sciam.com/article.cfm?id=moody-blood"}

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621with other data as part of our approach, it becomes apparent which genes have a lot of evidence for, and which not. The more lines of evidence implicating a gene, the more likely it is involved in bipolar disorder. It is sort of like the Google approach, where the more links to a page on the internet, the more likely it is it will come up at the top of your search list.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"We also were able to analyze how these genes work together and come up with a comprehensive biological understanding of what bipolar disorder is all about, from an evidence-driven perspective as opposed to a theoretical or speculative one. Before, different studies, by us and others, were uncovering different aspects of bipolar disorder - sort of like the parable of the blind men and the elephant. Now we have an idea for the first time of what the whole elephant might look like. A lot of the pieces of the puzzle are now making sense and falling into place."]})},{question:"What were the main findings?",answer:(0,_i.jsxs)(ds,{children:[(0,_i.jsxs)(ps,{children:[(0,_i.jsx)("strong",{children:"First:"})," Based on this work, we now project that there are going to be hundreds of genes involved in this illness, possibly as much as 10% of the genome. Not all gene mutations occur in every individual with bipolar - different individuals will have different combinations of genes. Still, this genetic complexity is likely what made past attempts to identify genes for the disorder through genetic-only studies so difficult and inconsistent. There is so much genetic diversity that huge population studies, possibly requiring hundreds of thousands of participants, would be needed to get statistically significant results for a large number of these bipolar genes. Most studies to date have used at most a few thousand subjects."]}),(0,_i.jsxs)(ps,{children:[(0,_i.jsx)("strong",{children:"Second:"})," Even though we used experimental data (genetic, gene expression, human and animal models) from studies of bipolar disorder, some of the top genes and pathways identified are also involved in other brain disorders (like schizophrenia or, surprisingly, Alzheimer Disease) as well as non-neuropsychiatric disorders like cancer. So there are shared genes and mechanisms with other disorders, which has potentially huge implications."]})]})},{question:"What would be the advantages of identifying these genes?",answer:(0,_i.jsxs)(_i.Fragment,{children:["First, a better understanding of bipolar disorder and related disorders. Second, we will be able to go back in individuals and study which combination of genes is present in what individual, to come up with a genetic risk score. So even before the illness manifests itself, preventive measures - lifestyle changes, counseling, even low dose medications - can be used to delay or abrogate the illness from developing. Third, in individuals who already have the illness manifested, genetic testing, in combination with blood biomarkers of disease state, can help inform which treatment works or not, reducing costly and distressing trials and errors.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"The bottom line is that a lot more work needs to be done to validate and understand these findings - in different populations, to look at gender differences, effects of environmental variables, etc. This is big science, and in the current environment, where the federal funding for science is flat or declining, philanthropy can make a huge impact in moving things forward fast, for the benefit of patients and their families."]})},{question:"Contact Information",answer:(0,_i.jsxs)(_i.Fragment,{children:["Alexander B. Niculescu III, MD, PhD",(0,_i.jsx)("br",{}),"Professor of Psychiatry, Founding Director, C4P (Center for Precise, Personalized, and Preventive Psychiatry)",(0,_i.jsx)("br",{}),"The University of Arizona College of Medicine \u2013 Phoenix",(0,_i.jsx)("br",{}),"Staff Psychiatrist and R&D Investigator, Carl T. Hayden VA Medical Center",(0,_i.jsx)("br",{}),"Email: ",(0,_i.jsx)("a",{href:"mailto:[email protected]",children:"[email protected]"})]})}];return(0,_i.jsxs)(ss,{children:[(0,_i.jsx)(ls,{children:"First Comprehensive Map Of Genes Likely To Be Involved In Bipolar Disorder FAQ"}),e.map(((e,t)=>(0,_i.jsxs)("div",{children:[(0,_i.jsx)(cs,{children:e.question}),(0,_i.jsx)(us,{children:e.answer})]},t)))]})},fs=Ei.div`
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644`;const vs=function(){const e=[{question:"Can you summarize your current research?",answer:(0,_i.jsxs)(_i.Fragment,{children:["We found patterns of change in the blood that reflect whether a person has low mood (depression) or high mood. These changes occur at the level of gene expression (how active a gene is) and involve genes previously thought to act primarily in the brain.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}

644),"Unlike cases of cancer, you can\u2019t biopsy the target organ (brain) in psychiatry. Having a readily accessible peripheral readout for blood would be great - even better (i.e., easier) than having a readout for cerebro-spinal fluid (CSF), which has been another area studied. However, such study requires a painful procedure for the patient (spinal tap).",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"Gene expression is more informative than genetic mutations in DNA - especially in terms of disease state - as it reflects gene activity. It is the place where rubber-meets-the-road in terms of gene-environment interactions: effects of drugs, stress, and medications. It may be more informative to know your biomarkers than to have your genome sequenced."]})},{question:"What are the advantages of a blood test for mood disorders?",answer:(0,_i.jsxs)(_i.Fragment,{children:["In psychiatry, we currently rely on patients\u2019 self-reported symptoms, as well as the clinician\u2019s impression. Patients are not sure as to the severity of their illness, and neither is the clinician (sometimes dismissing patients' symptoms, sometimes overestimating them). I am a psychiatrist as well as a researcher, and I often face that dilemma in my own clinical practice, where I see complicated cases.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"Having an objective test to measure disease state, severity, and (especially) response to treatment would be a big step forward. Such a measure would be similar to your primary care doctor or cardiologist ordering a baseline lipid panel, starting you on a medication, and conducting repeat lab testing to see how well the medication is working. It would place psychiatry on par with other medical specialties.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"For example, nowadays for depression, a patient gets started on an antidepressant. Weeks or months may pass before the patient and doctor know if the particular medication is working or if a different antidepressant should be administered. A blood test for mood state could objectively reflect the efficacy of current treatment. Perhaps changes in the blood could be caught early on, reducing the duration of uncertainty (trial and error). Knowing early on that a medication is moving things in the right direction is reassuring - and frankly - therapeutic to patients. Hope and optimism are powerful (yet poorly understood) neurobiological players: we know this due to the high rate of initial placebo responses with antidepressants.",(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"Another example: a patient is diagnosed as depressed but is actually bipolar (manic-depressive); this is a common problem. The patient may be started on an antidepressant initially, and if bipolar, will be flipped by the antidepressant into a mixed state or frank mood elevation (hypomania or mania). Patients could be monitored with a panel of mood-state markers after they have begun taking an antidepressant. If these markers indicate a shift to elevated mood, several interventions can be employed: medications can be changed; a mood stabilizer added to the regimen. A potentially dangerous - and certainly, miserable - episode for the patient can be averted."]})},{question:"Aside from depression and bipolar disorder, what other diseases could these findings diagnose?",answer:(0,_i.jsxs)(_i.Fragment,{children:['Mood state is important and sometimes overlooked in favor of complex disorders: postpartum depression (trivialized as "baby blues"), post-traumatic stress disorder, depression following myocardial infarction and cardiovascular procedures, depression associated with cancer, fibromyalgia, and mood changes associated with other serious diseases. Having an objective measure would expedite appropriate attention and treatment to patients.',(0,_i.jsx)("br",{}),(0,_i.jsx)("br",{}),"We are also doing similar work in schizophrenia, looking for blood markers associated with delusions and hallucinations. Schizophrenia is a complex disorder, with subjectivity and uncertainty about illness severity contributing to its intricacy. We are excited about our unpublished findings in this area and hope to quickly advance such work. NIH funding is on the decline these days. I think philanthropy can play a major role in funding such early-stage, unconventional research."]})},{question:"Two drugs were found to exert similar effects on both high and low mood. Can you expound on the implications of this and how this data could aid drug development?",answer:(0,_i.jsx)(_i.Fragment,{children:"In brief: we are looking at patterns changed in the blood with relationship to mood state and comparing these pattern changes with a database at the Broad Institute at MIT (containing signature patterns of a large number of known drugs). Using the database, we can ascertain which drugs exert a similar effect. The database might suggest new drugs (or at least chemical structures to be tweaked and developed by pharmaceutical companies) to be explored in the treatment of mood disorders."})},{question:"Can you expound on the implications of the overlap between some genes identified in your study and those involved in cancer?",answer:(0,_i.jsx)(_i.Fragment,{children:'It is a surprise to us, and we do not want to over-interpret it. Other colleagues in the field (Husseini Manji at NIMH, Francine Benes at Harvard, Huda Akil, colleagues at Michigan, and others) obtained similar results, and now the full picture is beginning to make sense. Nature is a tinkerer and has a limited number of building blocks at its disposal: nature seems to be re-using some of the same molecules used for "lower" functions (such as cell proliferation and cell death) and higher mental functions (such as mood regulation).'})}];return(0,_i.jsxs)(fs,{children:[(0,_i.jsx)(ms,{children:"Mood Biomarkers FAQ"}),e.map(((e,t)=>(0,_i.jsxs)("div",{children:[(0,_i.jsx)(gs,{children:e.question}),(0,_i.jsx)(ys,{children:e.answer})]},t)))]})},bs=Ei.div`
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