Peer Review #1 of "Integrating precision medicine in the study and clinical treatment of a severely mentally ill person (v0.2)"

Jason O'Rawe(Cold Spring Harbor Laboratory), Han Fang(Stony Brook University), Shawn Rynearson(University of Utah), Reid Robison(Foundation for Biomedical Research), Edward S. Kiruluta(Omicia (United States)), Gerald A. Higgins, Karen Eilbeck(University of Utah), Martin Reese(Omicia (United States)), Gholson J. Lyon(University of Utah), A Hoflich, M Savli, E Comasco, U Moser, K Novak, S Kasper, R Lanzenberger, A Torres, A Ramos-Cerqueira, Y Ferrao, L Fontenelle, M Do Rosario, E Miguel, P Alonso, C Segalas, E Real, A Pertusa, J Labad, S Jimenez-Murcia, N Jaurrieta, B Bueno, J Vallejo, J Menchon, V Balci, L Sevincok, D Roh, W Chang, J Chang, C Kim, W Goodman, R Alterman, P Blomstedt, R Sjoberg, M Hansson, O Bodlund, M Hariz, A Burdick, K Foote, M Mian, M Campos, S Sheth, E Eskandar, W Haynes, L Mallet, W Goodman, K Foote, B Greenberg, N Ricciuti, R Bauer, H Ward, N Shapira, S Wu, C Hill, S Rasmussen, M Okun, D Denys, M Mantione, M Figee, P Van Den Munckhof, F Koerselman, H Westenberg, A Bosch, R Schuurman, R Komotar, S Hanft, E Connolly, Jr, F Jimenez-Ponce, F Velasco-Campos, G Castro-Farfan, H Nicolini, A Velasco, R Salin-Pascual, D Trejo, J Criales, D Denys, M Mantione, A Burdick, W Goodman, K Foote, D Shah, A Pesiridou, G Baltuch, D Malone, J O'reardon, M Figee, J Luigjes, R Smolders, C Valencia-Alfonso, G Van Wingen, B De Kwaasteniet, M Mantione, P Ooms, P De Koning, N Vulink, N Levar, L Droge, P Van Den Munckhof, P Schuurman, A Nederveen, W Van Den Brink, A Mazaheri, M Vink, D Denys, N Lipsman, P Gerretsen, C Torres, A Lozano, P Giacobbe, N Lipsman, J Neimat, A Lozano, G Lyon(University of Utah), K Wang, G Lyon(Cold Spring Harbor Laboratory), J Segal, S Friend, L Peterson, R Kedl, L Dragone, M Zhu, A Need, Y Han, D Ge, J Maia, Q Zhu, E Heinzen, E Cirulli, K Pelak, M He, E Ruzzo, C Gumbs, A Singh, S Feng, K Shianna, D Goldstein, M Reese(Omicia (United States)), B Moore, C Batchelor, F Salas, F Cunningham, G Marth, L Stein, P Flicek, M Yandell, K Eilbeck(University of Utah), W Goodman, L Price, S Rasmussen, C Mazure, R Fleischmann, C Hill, G Heninger, D Charney, W Goodman, L Price, S Rasmussen, C Mazure, P Delgado, G Heninger, D Charney, S Gillihan, M Williams, E Malcoun, E Yadin, E Foa, B Greenberg, D Malone, G Friehs, A Rezai, C Kubu, P Malloy, S Salloway, M Okun, W Goodman, S Rasmussen, G Maina, G Rosso, R Zanardini, F Bogetto, M Gennarelli, L Bocchio-Chiavetto, D Hall, A Dhilla, A Charalambous, J Gogos, M Karayiorgou, A Rosa, M Cuesta, M Fatj-Vilas, V Peralta, A Zarzuela, L Faans, F Soliman, C Glatt, K Bath, L Levita, R Jones, S Pattwell, D Jing, N Tottenham, D Amso, L Somerville, H Voss, G Glover, D Ballon, C Liston, T Teslovich, T Van Kempen, F Lee, B Casey, M Davis, J Moscarello, J Ledoux, J Rodriguez-Romaguera, F Do Monte, G Quirk, C Montag, M Reuter, B Newport, C Elger, B Weber, J Lau, D Goldman, B Buzas, C Hodgkinson, E Leibenluft, E Nelson, L Sankin, D Pine, M Ernst, N Allen, S Bagade, M Mcqueen, J Ioannidis, F Kavvoura, M Khoury, R Tanzi, L Bertram, T Frayling, C Correll, P Manu, V Olshanskiy, B Napolitano, J Kane, A Malhotra, R Van Winkel, T Moons, O Peerbooms, B Rutten, J Peuskens, S Claes, J Van Os, M De Hert, D Collip, R Van Winkel, O Peerbooms, T Lataster, V Thewissen, M Lardinois, M Drukker, B Rutten, J Van Os, I Myin-Germeys, I Dumontheil, C Roggeman, T Ziermans, M Peyrard-Janvid, H Matsson, J Kere, T Klingberg, B Lajin, A Alachkar, A Hamzeh, R Michati, H Alhaj, A Raznahan, D Greenstein, Y Lee, R Long, L Clasen, P Gochman, A Addington, J Giedd, J Rapoport, N Gogtay, P Lopez-Garcia, L Young Espinoza, P Molero Santos, J Marin, F Ortuno Sanchez-Pedreno, J Singh, J Volavka, P Czobor, R Van Dorn, E Ira, M Zanoni, M Ruggeri, P Dazzan, S Tosato, Comt, J Roffman, R Gollub, V Calhoun, T Wassink, A Weiss, B Ho, T White, V Clark, J Fries, N Andreasen, D Goff, D Manoach, P Alonso, C Lopez-Sola, M Gratacos, M Fullana, C Segalas, E Real, N Cardoner, C Soriano-Mas, B Harrison, X Estivill, J Menchon, D Mancama, I Mata, R Kerwin, M Arranz, M Lundblad, K Stark, E Eliasson, E Oliw, A Rane, S Sim, M Ingelman-Sundberg, D Nelson, D Zeldin, S Hoffman, L Maltais, H Wain, D Nebert, T Pigott, S Seay, T Pigott, M Pato, S Bernstein, G Grover, J Hill, T Tolliver, D Murphy, B Ring, J Eckstein, J Gillespie, S Binkley, M Vandenbranden, S Wrighton, S Zhou, J Liu, B Chowbay, M Johnson, K Wang, S Tillmanns, N Albin, R Diasio, S Shestopal, M Johnson, R Diasio, J Sacco, M Abouraya, A Motsinger-Reif, S Yale, C Mccarty, L Trepanier, V Bozok Cetintas, O Erer, B Kosova, I Ozdemir, N Topcuoglu, S Aktogu, Z Eroglu, J Conn, D Protti, P Groen, P Kuzmak, R Dayhoff, S Brown, M Lincoln, P Groen, R Kolodner, --U Vista, J Fins, G Dorfman, J Pancrazio, M Synofzik, J Fins, T Schlaepfer, J Fins, T Schlaepfer, B Nuttin, C Kubu, T Galert, V Sturm, R Merkel, H Mayberg, J Fins, H Mayberg, B Nuttin, C Kubu, T Galert, V Sturm, K Stoppenbrink, R Merkel, T Schlaepfer, J Fins, N Schiff, J Fins, C Erickson-Davis, T Kim, J Mccall, Y Jung, X Huang, E Siuda, Y Li, J Song, Y Song, H Pao, R Kim, C Lu, S Lee, I Song, G Shin, R Al-Hasani, S Kim, M Tan, Y Huang, F Omenetto, J Rogers, M Bruchas, A Alivisatos, A Andrews, E Boyden, M Chun, G Church, K Deisseroth, J Donoghue, S Fraser, J Lippincott-Schwartz, L Looger, S Masmanidis, P Mceuen, A Nurmikko, H Park, D Peterka, C Reid, M Roukes, A Scherer, M Schnitzer, T Sejnowski, K Shepard, D Tsao, G Turrigiano, P Weiss, C Xu, R Yuste, X Zhuang, A Alivisatos, M Chun, G Church, K Deisseroth, J Donoghue, R Greenspan, P Mceuen, M Roukes, T Sejnowski, P Weiss, R Yuste, Neuroscience, M Pais-Vieira, M Lebedev, C Kunicki, J Wang, M Nicolelis, E Thomson, R Carra, M Nicolelis, M Nicolelis, A Moreno-De-Luca, S Myers, T Challman, D Moreno-De-Luca, D Evans, D Ledbetter, R Nielsen, J Paul, A Albrechtsen, Y Song, J O'rawe(Stony Brook University), T Jiang, G Sun, Y Wu, W Wang, J Hu, P Bodily, L Tian, H Hakonarson, W Johnson, Z Wei, K Wang, G Lyon(Cold Spring Harbor Laboratory), L Klei, S Sanders, M Murtha, V Hus, J Lowe, A Willsey, D Moreno-De-Luca, T Yu, E Fombonne, D Geschwind, D Grice, D Ledbetter, C Lord, S Mane, C Lese Martin, D Martin, E Morrow, C Walsh, N Melhem, P Chaste, J Sutcliffe, M State, E Cook, Jr, K Roeder, B Devlin, K Mitchell, D Porteous, K Mitchell, P Visscher, M Goddard, E Derks, N Wray, B Biesecker, H Peay, G Lyon(University of Utah), J Yu, S Jamal, H Tabor, M Bamshad, G Lyon(Stony Brook University), O Sacks, J Van Horn, A Irimia, C Torgerson, M Chambers, R Kikinis, A Toga, P Ratiu, I Talos, S Haker, D Lieberman, P Everett, H Eichenbaum, H What, Us, E Worthey, A Mayer, G Syverson, D Helbling, B Bonacci, B Decker, J Serpe, T Dasu, M Tschannen, R Veith, M Basehore, U Broeckel, A Tomita-Mitchell, M Arca, J Casper, D Margolis, D Bick, M Hessner, J Routes, J Verbsky, H Jacob, D Dimmock
Unknown
October 3, 2013
10.7287/peerj.177v0.2/reviews/1
Cited by 0Open Access
Full Text

Abstract

Integrating precision medicine in the study and clinical treatment of a severely mentally ill personBackground: In recent years, there has been an explosion in the number of technical and medical diagnostic platforms being developed.This has greatly improved our ability to more accurately, and more comprehensively, explore and characterize human biological systems on the individual level.Large quantities of biomedical data are now being generated and archived in many separate research and clinical activities, but there exists a paucity of studies that integrate the areas of clinical neuropsychiatry, personal genomics and brainmachine interfaces.Methods: A single person with severe mental illness was implanted with the Medtronic Reclaim® Deep Brain Stimulation (DBS) Therapy device for Obsessive Compulsive Disorder (OCD), targeting his nucleus accumbens / anterior limb of the internal capsule.Programming of the device and psychiatric assessments occurred in an outpatient setting for over two years.His genome was sequenced and variants were detected in the Illumina Whole Genome Sequencing Clinical Laboratory Improvement Amendments (CLIA)certified laboratory.Results: We report here the detailed phenotypic characterization, clinicalgrade whole genome sequencing (WGS), and two-year outcome of a man with severe OCD treated with DBS.Since implantation, this man has reported steady improvement, highlighted by a steady decline in his Yale-Brown Obsessive Compulsive Scale (YBOCS) score from ~38to a score of ~25.A rechargeable Activa RC neurostimulator battery has been of major benefit in terms of facilitating a degree of stability and control over the stimulation.His psychiatric symptoms reliably worsen within hours of the battery becoming depleted, thus providing confirmatory evidence for the efficacy of DBS for OCD in this person.WGS revealed that he is a heterozygote for the p.Val66Met variant in BDNF, encoding a member of the nerve growth factor family, and which has been found to predispose carriers to various psychiatric illnesses.He carries the p.Glu429Ala allele in methylenetetrahydrofolate reductase (MTHFR) and the p.Asp7Asn allele in ChAT, encoding choline Oacetyltransferase, with both alleles having been shown to confer an elevated susceptibility to

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