2019 Young Investigator Grant Program 2 Young Investigator Grant Program 2019 suicide prevention, as well as new applications in depression, in depression, applications new as well prevention, as suicide schizophrenia, PTSD, including ADHD, of disorders range wide by this year’s in a grantees employed are being non-invasively, brain, the that stimulate in technologies advances note how to is important it example, For ago. afew years just made that could have not been explorations are possible making insights to new of areas great promise, in which attention call taken together, possible.” projects, science 200 best These advancing of “the ourmission reflects grantees Investigator of Scientific Council’s the selection Young years, in past As forward. neuroscience and psychiatry of fields the move help will that advances and insights future provide will projects research These technologies. new and tools, diagnostic therapies, for ideas novel on focusing are specifically Others projects. research basic are pursuing grantees Investigator strategy, manyContinuing our of growth scientific our Young follow. that summarized pages in the projects research meritorious 200 the selected and applications than 900 more reviewed area of brain research, in every expertise with scientists of 184 world-renowned comprised and Pardes Dr. Herbert year,This Foundation’s the Scientific by Council,led translational, researchers. clinical and basic, supports and opportunities research innovative facilitates program This research. psychiatric and neurobiological conducting scientists young promising most for the support provides in 1987,Initiated Young Grant BBRF the program Investigator in brain innovative research. ideas best the of range abroad represent of group scientists extraordinary Young This Foundation Grantees. Research Investigator 2019 to to the you present We are pleased Brain &Behavior 2019 October “BBRF Young Investigators represent who willpioneerbreakthroughs insights tounderstanding,treating, in mentalhealthresearch. We are excited to be able to support theworkexcited tobeablesupport and curingmentalillness.” apply powerful newtechnologiesand a newgeneration ofresearchers of theseyoung scientists,whowill President &CEOPresident M.D. Borenstein, Jeffrey Sincerely, full, live can lives. happy, people productive and more so search for cures, new treatments, of and methods prevention in the scientists continue to can we support help your With expenses are covered by separate foundation grants. operating Our grants. research our in invested is research 100% scientist. young promising of every dollar donated for of a career in the is investment an it project, research innovative Agrant to aYoung funds an only not scientists. Investigator and donors generous between is acollaboration BBRF globally. scientists to 4,896 grants in million research than $408 more that since 1987 We to have are we proud report provided across disorders. networks and brain circuits “helpers”—in mere thought malfunctioning of glia astrocytes—long involvement and possible the and “clocks” disturbances; sleep of biological that may underlie pleasure); workings the to experience (the inability anhedonia to rise that gives circuitry the understanding deficits; cognitive of treating ways stress; of early-life impact the focusing on research include examples Some muchin evidence. very also is disorders in multiple that has importance Research Basic potential. great technology’s this hinted at late in first the 1990s grants Foundation in which

bbrfoundation.org 3

Perry F. Renshaw, M.D., Ph.D., M.B.A. Ph.D., M.D., Renshaw, F. Perry Ph.D. M.D., Ressler, J. Kerry Ph.D. Risbrough, Victoria B. M.D. Robinowitz, Carolyn B. Ph.D. M.D., Roth, L. Bryan Ph.D. Rowland, M. Laura Ph.D. M.D., Rubenstein, John L.R. Ph.D. M.D., Bernardo Sabatini, Ph.D. M.D., Sanacora, Gerard Ph.D. M.D., Sawa, Akira M.D. Schatzberg, Alan F. Ph.D. Schooler, Nina R. Ph.D. Robert Schwarcz, M.D. Sheline, Yvette I. M.D., Snyder, Solomon H. Causa) (Hon. D.Phil. D.Sc., Ph.D. M.D., Sohal, Vikaas S. Ph.D. M.D., State, W. Matthew M.P.H., M.D., Stein, B. Murray F.R.C.F.C. M.D. Strakowski, Stephen M. M.D. Strauss, John S. Ph.D. David Sweatt, J. M.D. Talbott, John A. M.D. Tamminga, Carol A. Ph.D. M.D., Tecott, Laurence H. Ph.D. Tye, Kay M. Ph.D. Ungerleider, Leslie G. M.D. Vaccarino, M. Flora Ph.D. Valentino, Rita J. M.D. Veenstra-VanderWeele, Jeremy M. Ph.D. M.D., Voglmaier, Susan M. Ph.D. M.D., Voineskos, Aristotle N. M.D. Volkow, D. Nora Ph.D. M.D., Wagner, Karen Dineen M.D. Weinberger, Daniel R. Ph.D. Weissman, Myrna M. Ph.D. Wolf, Marina E. Ph.D. Young, W. Jared Ph.D., M.D., Young, Trevor L. F.C.A.H.S. F.R.C.P.C., M.D. Jr., Zarate, A. Carlos Ph.D. M.D., Jon-Kar Zubieta, MEMBERS EMERITUS M.D. Aghajanian, George K. Ph.D. BJ Casey, M.D. Charney, Dennis S. M.D. Fawcett, A. Jan M.D. Goodwin, K. Frederick Ph.D. Kidd, K. Kenneth Ph.D. M.D., Philip Seeman, D.Sc. Ph.D., M.D., Tsuang, T. Ming MRCPsych Ph.D., M.D., Os, Jim van Ph.D. M.D., Mark von Zastrow, Richard S.E. Keefe, Ph.D. Keefe, Richard S.E. M.D. Keith, Samuel J. M.D. Keller, Martin B. M.D. Kelsoe, John R. M.D. Kendler, S. Kenneth M.D. Kennedy, L. James M.D. Kessler, Robert M. Ph.D. Mary-Claire King, Ph.D. Klein, Rachel G. M.D. Krystal, John H. Ph.D. Law, Amanda J. Ph.D. M.D., Leckman, F. James Ph.D. M.D., Lee, S. Francis M.D. Ellen Leibenluft, M.D. Lenox, Robert H. Ph.D. Levitt, R. Pat M.D. Lewis, A. David M.D. Lieberman, A. Jeffrey M.D. Lim, Kelvin M.D. Luby, Joan L. Ph.D. Irwin Lucki, Ph.D. Gary Lynch, Ph.D. M.D., Malenka, Robert C. M.D. Malhotra, Anil K. F.R.C.P.C. M.D., Manji, Husseini K. M.D. John Mann, J. M.P.H. M.D., March, John S. Ph.D. Stephen Maren, M.D. Ph.D., Mathalon, Daniel H. M.D. Mayberg, Helen S. Ph.D. McEwen, Bruce S. Ph.D. Ronald McKay, M.D. Meador-Woodruff, H. James M.D. Meltzer, Y. Herbert Ph.D. Merikangas, Kathleen R. Ph.D. Miller, Richard J. Ph.D. M.D., Karoly Mirnics, Ph.D. Bita Moghaddam, Ph.D. Monteggia, Lisa M. Ph.D. M.D., Nemeroff, Charles B. Ph.D. M.D., Nestler, Eric J. M.D. Nierenberg, A. Andrew Ph.D. M.D., O’Donnell, Patricio Ph.D. M.D., Dost Ongur, Ph.D. M.D., Oquendo, A. Maria M.D. Paul, Steven M. Ph.D. M.D., Pearlson, Godfrey D. (CANTAB) M.D. M.D., Phillips, Mary L. Ph.D. Picciotto, Marina R. M.D. Pine, Daniel S. M.D. Post, Robert M. M.P.H. M.D., Potash, B. James M.D. Potkin, Steven G. Ph.D. M.D., Rakic, Pasko M.D. Rapoport, Judith L. Joseph T. Coyle, M.D. Coyle, T. Joseph Ph.D. Crawley, N. Jacqueline M.D. Csernansky, John G. Ph.D. M.D., Jeff Daskalakis, Z. Ph.D. M.D., Karl Deisseroth, M.D. Jr., DePaulo, Raymond J. Ph.D. Deutch, Y. Ariel Ph.D. Ralph DiLeone, M.P.H. M.D., Lisa Beth Dixon, M.D. Drevets, C. Wayne Ph.D. Duman, Ronald S. Ph.D. Guoping Feng, MBA M.D., Findling, Robert L. Ph.D. Floresco, Stan B. Ph.D. Ford, Judith M. Ph.D. Alan Frazer, M.D. Robert Freedman, Ph.D. Gage, H. Fred Ph.D. Aurelio Galli, M.D. George, Mark S. M.D. Gershon, Elliot S. Ph.D. Geyer, A. Mark M.D. Giedd, N. Jay Ph.D. M.D., Gingrich, A. Jay Ph.D. Gold, M. James M.D. David Goldman, Ph.D. M.D., Gordon, A. Joshua Ph.D. Elizabeth Gould, Ph.D. Grace, A. Anthony Ph.D. M.D., Gur, Raquel E. Ph.D. Haber, Suzanne N. Ph.D. Harvey, Philip D. M.D. Stephan Heckers, Ph.D. René Hen, Ph.D. M.D., Henn, A. Fritz Ph.D. Hensch, K. Takao M.D. Hirschfeld, Robert M.A. M.D. Elliot Hong, Ph.D. Hurd, L. Yasmin M.D. Hyman, Steven E. Ph.D. M.D., Innis, Robert B. Ph.D. M.D., Javitch, A. Jonathan Ph.D. M.D., Javitt, Daniel C. M.D. Jeste, V. Dilip M.D. Kalin, Ned H. Ph.D. Kalivas, W. Peter M.D. Kandel, Eric R.

Recipients of the National Medal of Science of the National Medal Recipients of Mental of the National Institute Former Directors Director Health and the current Nobel Prize Winner Members (11 Emeritus) Members of Medicine of the National Academy Members Departments Psychiatry & Neuroscience Chairs of of Sciences of the National Academy Members 4 3 1 53 29 12 Ted Abel, Abel, Ph.D. Ted Anissa Abi-Dargham, M.D. Ph.D. M.D., Ahmari, Susanne E. Akbarian, Schahram M.D.,Ph.D. Huda Akil, Ph.D. Ph.D. Amara, Susan G. Anderson, M.D. A. Stewart Ph.D. M.D., Andreasen, Nancy C. Ph.D. Victoria Arango, Arlotta, Ph.D. Paola Ph.D. Arnsten, Amy F.T. Ph.D. Aston-Jones, Gary S. Ph.D. M.D., Baraban, M. Jay Ph.D. Barch, Deanna M. M.D. Barchas, D. Jack M.D. Barondes, Samuel H. Ph.D. Bearden, Carrie E. Ph.D. M.D., Benes, M. Francine M.D. Berman, Karen F. Ph.D. M.D., Berrettini, H. Wade Ph.D. Blakely, Randy D. Ph.D. M.D., Pierre Blier, M.D. Blumberg, Hilary P. M.D. Antonello Bonci, Ph.D. Brennand, Kristen J. M.D. Buchanan, W. Robert M.D. Buckley, F. Peter Ph.D. Bullmore, T. Edward M.D. Jr., Bunney, William E. Ph.D. Buxbaum, Joseph D. M.D. William Byerley, Ph.D. Cannon, D. Tyrone Ph.D. William Carlezon, Ph.D. Caron, Marc G. M.D. Jr., Carpenter, T. William M.D. Carter, Cameron S. Ph.D. M.D., Cohen, Bruce M. Ph.D. M.D., Cohen, Jonathan D. Ph.D. Jeffrey Conn, Peter M.D. Jr. Cook, Edwin H. D.Sc. Richard Coppola, Floyd E. Bloom, M.D. Bloom, Floyd E. Herbert Pardes, M.D. Herbert Pardes, VICE PRESIDENT EMERITUS PRESIDENT BBRF SCIENTIFIC COUNCIL SCIENTIFIC BBRF 184

4 Young Investigator Grant Program 2019 SELECTION COMMITTEE OF THE YOUNG INVESTIGATORCO-CHAIRS GRANT BBRF ScientificCouncil Member 2003 BBRFIndependent Investigator University ofCalifornia,SanFrancisco Professor, DepartmentofPsychiatry Ph.D. Ford, Judy M. BBRF ScientificCouncil Member 2011 BBRFDistinguished Investigator University ofRochesterSchool of MedicineandDentistry Professor, DepartmentofPharmacologyandPhysiology Suzanne Haber, N. Ph.D. BF on Investigator Young “BBRF NewYork-PresbyterianHospital Trustees of

mental illness.Theseearly- research, early intervention technologies, andnext- that hasimproved the brain andbehaviordisorders.” lives ofpeoplelivingwith significant stridesinbasic generation therapies thatwill groundbreaking research grants have ledto offer thebesthopeforchange career scientistsare making and advances intreatments for and diagnostictools,new Executive Vice ChairmanoftheBoardExecutive Vice President oftheBBRFScientific Council Herbert Pardes, M.D.

bbrfoundation.org 5 that aim aim that GRANTS IN YOUNG that will power both basic both power will that $13.8 INVESTIGATOR MILLION AWARDED MILLION AWARDED , the wellspring of innovation in in innovation of wellspring , the GRANTS FUNDED new technologies new About 69 percent of the projects the of are About percent funded 69 researchbasic sciences. all in as research brain projects the of are percent funded About 15 intervention tools/early diagnostic to prevent brain and behavior disorders. behavior and brain prevent to projects of About development the 3 percent fund of new developments clinic. the and in research fund grants 2019 the of percent About 14 projectsto develop specificallyaim that therapies. next-generation $408M+ YOUNG GRANTS AWARDED 200 INVESTIGATOR INVESTIGATOR (29 Grants)

GRANTS AWARDED 5,900+ (7 Grants) YOUNG 943 APPLICATIONS INVESTIGATOR INVESTIGATOR Diagnostic Tools/Early Intervention Diagnostic Tools/Early ultimately cure and prevent brain and and prevent ultimately cure behavior disorders To reduce symptoms of mental illness and symptoms of mental reduce To treat as early as possible as early treat ways of studying new advance or create To and understanding the brain To recognize early signs of mental illness and early signs of recognize To cause mental illness (137 Grants) Basic Research understand what happens in the brain to To New Technologies Next Generation Therapies (27 Grants)

About 80 percent of grantees are from the United States (161 grantees). Twenty percent of grantees come from from come grantees of percent Twenty grantees). (161 States United the from are grantees About of 80 percent Japan, Australia, Brazil, France, Italy, The Switzerland, Netherlands, UK, the Germany, Canada, countries: other 16 China. of Republic People’s the and Sweden, Austria, Argentina, Spain, Ireland, The Foundation is pleased to announce over $13.8 million in 200 new two-year grant awards to support to 200 new two-year of in work the awards million grant $13.8 over announce pleasedThe is to Foundation research. health mental in ideas scientists with innovative young promising

RESEARCH CATEGORIES THE 2019 YOUNG INVESTIGATOR GRANTEES INVESTIGATOR YOUNG 2019 THE SINCE 1987 6 Young Investigator Grant Program 2019 Adele Stewart,Ph.D.. Fabian MunozSilva,Ph.D.. Joanna Martin,Ph.D. Claudia Lugo-Candelas,Ph.D.. Rachel Lean,Ph.D. Supriya Ghosh,Ph.D. Kimberly Chiew, Ph.D. Weidong Cai,Ph.D. Mariam Aly, Ph.D.. (ADHD) HYPERACTIVITY DINSORDER ATTENTION-DEFICIT USE DISORDERS ADDICTION /SUBSTANCE- Hideaki Yano, Ph.D. Ph.D. Corinde Wiers, Alessandra Vergallito, Ph.D. Samantha Scudder, Ph.D. Mina Rizk,M.D. Greg Perlman,Ph.D.. Daniela Neuhofer, Ph.D. Jacquelyn Meyers,Ph.D. Philipp Mews,Ph.D. Angela Mabb,Ph.D. Erica Jung,Ph.D.. Danique Jeurissen,Ph.D.. Andrea Hobkirk,Ph.D. Alexander Herman,M.D.,Ph.D. Matthew Hearing,Ph.D.. Felicity Gore, Ph.D. Kyle Flippo,Ph.D. Hanan ElMarroun, Ph.D. Johannes deJong,Ph.D.. Gregory Corder, Ph.D.. Luis Colon-Perez, Ph.D.. Daniel Christoffel, Ph.D. Erin Campbell,Ph.D.. Gerard Beaudoin,III,Ph.D. Maxime Assous,Ph.D.. Ream Al-Hasani,Ph.D. (sorted by category; some projects are relevant in multiple categories) INVENTORY OF PROJECTS: 2019 GRANTEES ......

...... 33 26 25 24 23 17 13 12 37 35 35 31 30 29 27 25 25 24 21 21 19 19 18 17 16 15 14 13 13 13 12 10 9 9 9 Madeleine Kyrke-Smith,Ph.D.. Benjamin Kleaveland,M.D.,Ph.D. . Tae HyunKim, Ph.D.. Magdalena Janecka,Ph.D. Moshen Jamali,M.D.,Ph.D. Jacque PakKanIp,Ph.D.. Suk JunHong,Ph.D.. Karina Genaro, Ph.D. Alicia Che,Ph.D.. Michael Cahill,Ph.D.. Shelly Buffington, Ph.D. Andre Ph.D. Berndt, (ASD) AUTISM SPECTRUMDISORDER Katherine Young, Ph.D.. Yuanzhong Xu,Ph.D. Alessandra Vergallito, Ph.D. Chelsea Vadnie, Ph.D.. Ph.D. Ashwini Tiwari, Samantha Scudder, Ph.D. Helen Schwerdt, Ph.D. Lindsay Schwarz,Ph.D.. David Root,Ph.D. Catherine Pena,Ph.D.. Agnes Norbury, Ph.D. Ciaran Murphy-Royal,Ph.D. Jordan McCall,Ph.D.. Joanna Martin,Ph.D. Angela Mabb,Ph.D. Elizabeth Lucas,Ph.D.. Daniel Levey, Ph.D. Munir Kutlu,Ph.D. Jesse Jackson,Ph.D. Melissa Herman,Ph.D. Adam Gorka,Ph.D.. Courtney Filippi,Ph.D. Dawn Eichen,Ph.D. Roman Dvorkin,Ph.D.. Laura DeNardo, Ph.D.. Gregory Corder, Ph.D.. George Buzzell,Ph.D.. Jeremy Borniger, Ph.D. Lauren Asarnow, Ph.D. Jessica Ables,M.D.,Ph.D.. Rany Abend,Ph.D. ANXIETY DISORDERS ...... 31 30 22 22 22 21 20 20 19 12 11 11 10 38 35 34 31 31 29 26 25 24 24 23 22 20 19 18 16 15 15 14 13 11 10 17 37 34 27 25 9 9 9 Jun Yokose, Ph.D. . Jingqi Yan, Ph.D. . Ph.D.. Leena Williams, Yi-Lan Weng, Ph.D.. Lu Wang, Ph.D.. Ph.D. Thomas Vierbuchen, Stefon vanNoordt, Ph.D. Anne Takesian, Ph.D. Steven Sloan,M.D.,Ph.D.. Christopher Rodgers,Ph.D.. Brian Rash,Ph.D. Mu Qiao,Ph.D.. Rui Peixoto,Ph.D.. Won ChanOh,Ph.D. Jason Nomi,Ph.D.. Ralda Nehme,Ph.D. Pierre Mattar, Ph.D.. Devanand Manoli,M.D.,Ph.D. Angela Mabb,Ph.D. Johannes Larsch,Ph.D. Thomas Vierbuchen, Ph.D. Thomas Vierbuchen, Chelsea Vadnie, Ph.D.. Yasuyuki Shima,Ph.D.. Andrey Shabalin,Ph.D.. Marcos Santoro, Ph.D. Brian Rash,Ph.D. Ralda Nehme,Ph.D. Amanda Lyall, Ph.D. Jessica Lipschitz,Ph.D. Munir Kutlu,Ph.D. Daniel Joyce,Ph.D. Danique Jeurissen,Ph.D.. Paul Jenkins,Ph.D. Moshen Jamali,M.D.,Ph.D. Muhammad Husain,MBBS,M.D. Philipp Homan,M.D.,Ph.D. Kristen Haut,Ph.D.. Danella Hafeman,M.D.,Ph.D. June Gruber, Ph.D. Chandramouli Chandrasekaran,Ph.D. Michele Bertocci,Ph.D.. Azmeraw Tayelgn Amare, Ph.D. BIPOLAR DISORDER ...... 35 37 37 36 35 35 35 33 32 30 29 29 29 28 27 27 25 25 24 23 35 22 21 21 18 34 32 31 29 27 24 21 20 18 18 12 10 31 24 20 19 9 bbrfoundation.org 7 9 11 12 14 15 19 21 23 31 33 34 36 37 38 10 14 14 16 17 17 19 22 24 24 25 27 30 30 31 31 31 33 34 36 ...... PSYCHOSIS Ph.D. Benjamin Buck, Ph.D. . . . . Simon Chamberland, . . . Ph.D. . . . . Alexis Cullen, . . . Ph.D. . . . . Sarah DuBrow, M.D., Ph.D. Philipp Homan, Ph.D. . . . Lana Kambeitz-Ilankovic, Ph.D...... Le Merre, Pierre Ph.D. Santoro, Marcos Ph.D. . . . . Karuna Subramaniam, ...... M.D. Sunny Tang, Ross Williamson, Ph.D. Ph.D...... Kun Yang, Ph.D...... Katherine Young, STRESS POST-TRAUMATIC DISORDER (PTSD) Ph.D...... Mariam Aly, Ph.D...... Jennifer Barredo, Ph.D...... Laura DeNardo, Deri, Ph.D...... Yael Ph.D. Fonzo, Gregory Ph.D...... Gabrielle Girardeau, Matthew Girgneti, Ph.D...... Ph.D...... Ann Hoffman, Munir Kutlu, Ph.D. Elizabeth Lucas, Ph.D...... Angela Mabb, Ph.D. Ph.D...... McCall, Jordan Ph.D. Agnes Norbury, David Root, Ph.D. Ryan, Ph.D. Tomas Lindsay Schwarz, Ph.D...... Ph.D. Helen Schwerdt, Shabalin, Ph.D...... Andrey Ph.D. Benjamin Suarez-Jimenez, Ashwini Tiwari, Ph.D. Jon Willie, M.D., Ph.D. 9 18 22 26 35 37 13 15 17 37 37 28 28 28 28 28 29 29 30 30 31 31 31 31 32 32 33 33 34 34 34 34 35 36 36 38 38 38 ...... now, Ph.D. now, Christoph Kraus, M.D., Ph.D. M.D., Ph.D...... Kai Miller, Ph.D. Allison Waters, Ph.D. Zeynep Yilmaz, OBSESSIVE-COMPULSIVE DISORDER (OCD) Matthew Hearing, Ph.D...... EATING DISORDERS EATING Asar Lauren Daniel Christoffel, Ph.D. Daniel Christoffel, Dawn Eichen, Ph.D. Ph.D. Felicity Gore, Xu, Ph.D. Yuanzhong Ph.D. Zeynep Yilmaz, Kieran O’Donnell, Ph.D. O’Donnell, Kieran Jason Oliver, Ph.D. Oliver, Jason Ph.D. Jocelien Olivier, . . . . . Ph.D. . . . . Alexey Ostroumov, . . Ph.D. . . . . Thomas Papouin, . . Pena, Ph.D. . . . . Catherine . . . . . Roseann Peterson, Ph.D...... Juliet Richetto, Ph.D. David Root, Ph.D. Shogo Sato, Ph.D...... Lindsay Schwarz, Ph.D. Ph.D. Helen Schwerdt, Shabalin, Ph.D...... Andrey Shan Siddiqi, M.D. Sandeep Singh, Ph.D. Ph.D...... Colenso Speer, Louisa Steinberg, M.D., Ph.D. Ashwini Tiwari, Ph.D. Ph.D...... Chelsea Vadnie, Ph.D...... Matilde Vaghi, M.D., Ph.D. Valiengo, Leandro Ph.D. Alessandra Vergallito, M.D., Ph.D. Christian Wozny, Ph.D. Wu, Yao Ph.D...... Katherine Young, Ph.D. Sanghee Yun, Xian Zhang, Ph.D...... 9 9 9 10 10 10 11 12 14 16 24 12 12 13 14 14 15 15 15 15 16 17 17 17 18 18 19 19 20 20 21 21 22 22 22 23 23 24 24 24 25 25 25 25 26 26 26 27 27 ...... Lauren Asarnow, Ph.D. Asarnow, Lauren Ph.D...... Jennifer Barredo, FRCPC Bhat, M.D., M.Sc., Venkat Ph.D. Borniger, Jeremy . M.P.H. Ph.D., Catherine Brownstein, Nadia Cattane, Ph.D. Robin Chan, Ph.D...... Ph.D. . . . . Emily Finn, Ph.D. Angela Mabb, DEPRESSION . . . . . Jessica Ables, M.D., Ph.D. Ph.D. Amare, Azmeraw Tayelgn Natali Chanaday Ricagni, Ph.D. . . . Ph.D. Daniel Christoffel, M.D., Ph.D., M.Sc. Federico Daray, Ph.D...... Laura DeNardo, Julien Dupuis, Ph.D. Ph.D. Natalia Duque-Wilckens, D.V.M., Dawn Eichen, Ph.D. Ph.D. Claudia Espinosa-Garcia, Emily Finn, Ph.D...... Bharathi Gadad, Ph.D. M.D. Damien Gallagher, Ph.D. Felicity Gore, Hanne Hansen, Ph.D. Matthew Hearing, Ph.D...... Melissa Herman, Ph.D. Philipp Homan, M.D., Ph.D. Ph.D...... Nicholas Hubbard, Rainbo Hultman, Ph.D. Daniel Joyce, Ph.D. Kageyama, M.D., Ph.D. . . . . Yuki Ph.D. Janine Knauer-Arloth, Christoph Kraus, M.D., Ph.D. Munir Kutlu, Ph.D. Ph.D. Daniel Levey, Laura Lewis, Ph.D...... Angela Mabb, Ph.D. Erika Manczak, Ph.D. Merry Mani, Ph.D...... Devanand Manoli, M.D., Ph.D. Joanna Martin, Ph.D. McCall, Ph.D...... Jordan Giorgia Michelini, Ph.D. Ph.D. Jean-Philippe Miron, Morris, Ph.D. Laurel Ciaran Murphy-Royal, Ph.D. Carla Nasca, Ph.D. Ralda Nehme, Ph.D...... Ph.D. Laura DeNardo, BORDERLINE PERSONALITY PERSONALITY BORDERLINE DISORDER 8 Young Investigator Grant Program 2019 Katherine Young, Ph.D.. Jingqi Yan, Ph.D.. Ph.D. Zachary Wills, Ph.D. Ross Williamson, Ph.D. Thomas Vierbuchen, Jorien Treur, Ph.D.. Karuna Subramaniam,Ph.D.. Steven Sloan,M.D.,Ph.D.. Tarjinder Singh,Ph.D. Andrey Shabalin,Ph.D.. Can Ruan,Ph.D.. Brian Rash,Ph.D. Mu Qiao,Ph.D.. Rui Peixoto,Ph.D.. Johannes Passecker, Ph.D.. Thomas Papouin,Ph.D.. Jason Olivier, Ph.D. Ralda Nehme,Ph.D. Jacquelyn Meyers,Ph.D. Devanand Manoli,M.D.,Ph.D. Felix Leroy, Ph.D.. Pierre LeMerre, Ph.D.. Johannes Larsch,Ph.D. Madeleine Kyrke-Smith,Ph.D.. Annie Kathuria,Ph.D.. Daniel Joyce,Ph.D. Danique Jeurissen,Ph.D.. Moshen Jamali,M.D.,Ph.D. Hailiang Huang,Ph.D.. James Howard, Ph.D. Philipp Homan,M.D.,Ph.D. Matthew Hearing,Ph.D.. Michael Francis,M.D. Ph.D. Antonio Fernandez-Ruiz, Kristen Delevich,Ph.D. Senthilkumar Deivasigamani,Ph.D.. Alexis Cullen,Ph.D.. Yao Chen,Ph.D.. Catherine Brownstein, Ph.D.,M.P.H. . Urs Andreas Braun,M.D. Bigdeli,Ph.D.. Tim SCHIZOPHRENIA ...... 38 37 36 36 35 34 33 32 32 31 30 29 29 29 29 28 28 27 25 25 23 23 23 22 22 21 21 20 20 19 19 18 16 16 14 14 14 13 11 11 10 (Neuronal Manipulation) Sangjin Yoo, Ph.D. (Coping Response) Matthew Wright, M.D.,Ph.D. (Circadian Regulation) (Cross-Disorder Trait Analysis) Tan HoangNguyen,Ph.D. (Population Screening) John Naslund,Ph.D.. disorders. These projectspertainbroadlytoall ALL DISORDERS Colenso Speer, Ph.D. (Brain Development) Andre Sousa,Ph.D. (Insulin Signaling) Maite Solas,Ph.D. (Multi-scale BrainActivity) Adam Snyder, Ph.D.. (Transposons andStress) Anindita Sarkar, Ph.D. (Memory Access) Tomas Ph.D.. Ryan, (Cortical Folding) Brian Rash,Ph.D.. (White MatterFormation) Stephanie Moon,Ph.D. (Cellular Development) Gilad Evrony, M.D.,Ph.D.. (Decision-Making) Chandramouli Chandrasekaran,Ph.D. works. These projectsfocusonhowthebrain BIOLOGY OFTHEBRAIN Sandeep Singh,Ph.D. Andrey Shabalin,Ph.D.. Mina Rizk,M.D. Jordan McCall,Ph.D.. Daniel Levey, Ph.D. Emily Diblasi,Ph.D.. Jennifer Barredo, Ph.D.. SUICIDE PREVENTION ...... 38 36 33 27 27 33 32 32 31 30 29 26 16 12 32 31 30 25 23 14 10 Christoph Kraus,M.D.,Ph.D. Parkinson’s Disease Jingqi Yan, Ph.D.. Benjamin Kleaveland,M.D.,Ph.D.. Jacque PakKanIp,Ph.D.. Karina Genaro, Ph.D. Fragile XSyndrome M.D.,Ph.D. Jon Willie, Ph.D. Corinde Wiers, Christoph Kraus,M.D.,Ph.D. Epilepsy Emmanuel Cruz-Torres, Ph.D. Angelman Syndrome Thomas Papouin,Ph.D.. Alzheimer’s Disease OTHER DISORDERS . . . . . 22 37 22 20 17 35 22 13 28 36 bbrfoundation.org 9 ------University Adelaide, of Stanford University, will Stanford study University, Rutgers University, will Rutgers University, investigate

Basic Research Basic Research Basic Research New Technologies

Next-Generation Therapies

ing hypothesizes interneurons She (THINs). that they are in mediatinginvolved the effectsdopamineof physio in logical, goal-oriented behavior and in response psycho to stimulants. Past results a critical to point THINs of role in contributing the to effectdopamineof in striatal circuitry; the new research a better could to contribute understanding theof cellular mechanisms action psychostimulants of of in the striatum and their relation addiction. to Lauren Asarnow, Ph.D., Asarnow, Lauren dersare who enrolled trialin a pilot examining theeffective designedphone-based sleepness app a mobile of improve to health. Relevant disorders anxiety, include and depression eating disorders, in all which of individuals internalize their The problems. aim determineto is whether improving sleep positively impacts markers inflammation. of The studythus provides a framework preventing for internalizing disorders in youths, with better the of hope understanding biological pathways that may be contributing risk. to Assous, Ph.D., Maxime dopamineof the inhibitory role modulation of a group of neurons in the striatum—tyrosine hydroxylase-express will fMRI involve scans healthy of participants will who take part in two sessions, in which one they abstain from nicotine cholinergic agonist) least at (a for hours and 12 another in which they ingest nicotine the to session. just prior Amare, Ph.D.,Azmeraw Tayelgn Australia, is exploring genes associated with treatment response in patients with mood disorders, using artificial intelligence (machine learning) methods algo develop to rithmsthat can beused personalizing for treatment. To investigate the genetic overlapping mechanisms underlying drugmultiple Amare response, Dr. will perform a bivari association functional by followed genome-wide ate study, pathway and network analysis genes, uncover to overlapping biological pathways, and molecular networks in involved response lithium to and antidepressant treatments. cellular markers inflammation of collected youthfrom 34 with sleep disturbances high at risk internalizing for disor - - - - Icahn Medicine School of at St. Louis St. College Pharmacy of and Ph.D.,

National Institute Mental of Health, Columbia University, will why explore Columbia University, Basic Research Basic Research

Diagnostic Intervention Tools/Early individualswith ADHD and PTSD are greater at risk for nicotine dependence, testing the hypothesis that nicotine may restore a disrupted balance between processes in the brain that attend internal to states and the external Aly Dr. world. will examine the effects of modulation cholinergic on the hippocampus, a brain in region both involved the retrieval internalof memories and the attention to external world, andwhich shows abnormalities in ADHD and This PTSD. peutic approaches addiction. to team The will focus how on dynorphin,the the peptide for kappa endogenous opioid in is the involved modulation natural of receptor, reward- and threat-like behaviors. Ph.D.,Mariam Aly, Washington University, willWashington peptide investigate University, opioid how levels and respond adapt natural to rewards and threats. This willinsight peptide modulation provide how is on altered in diseasestates, which in turn caninform alternative thera Ream Al-Hasani, Ph.D., informative than analyzing expressiongene inthe region asa that hoping sequencing whole, by and targeting specific cell types, may identify be to possible it a vulnerable population specificor pathway that may be targetednewdevelop to treatments and depression for anxiety. inmouse a diabetes. modelof Thesebrain areas beenhave shownbe to key inregulating mood and anxiety. Ables Dr. will specific at look cell types within each area, which more is Mount Sinai,Mount seeks determine to the effect of increasedblood sugar vulnerability on stress, to expression, gene structure and function neurons in of the striatum, habenula and midbrain Jessica Ables, M.D., Ables, Jessica clinical neuroscience research toward improving treatment pediatricfor anxiety disorders. tify a brain-based pediatric biomarker of anxiety treatment response. Establishing such a biomarker is an important step in understanding CBT treatment mechanismsand promoting grate translational neuroscience and clinical research iden to Rany Abend,Rany Ph.D., NIH, seeks cognitive elucidate to behavioral therapy (CBT) treatmentmechanisms. CBT is first-line peditreatment for atric anxiety, shows substantial but variability in treatment response, leaving many patients affected and underscoring project The outcomes. theaims need improve to to inte THE 2019 BBRF YOUNG INVESTIGATOR GRANTEES INVESTIGATOR BBRF YOUNG 2019 THE (in alphabetical order) 10 Young Investigator Grant Program 2019 mechanisms in people. in mechanisms for possible to intervention provide comprehensive insights applications pharmacological through states brain impaired with animals in function to restore aim They stimulation. the of specificity cell-type and frequency, length, on timing, depending states brain alter permanently can signals diated chloride-me impaired that hypothesizes The team emerge. states neuropathological permanent which under minants deter the physiological reveal is to goal The zebrafish. in development, early in circuits brain intact in signaling ated anovel chloride-medi optogeneticuse approach to study will disorders, developmental other and ASD in interested in paying attention when we are performing mental tasks. tasks. mental performing attention when we are paying in and at rest is brain when the engaged is which precuneus, the called area oft-neglected the study to disorder. bipolar She will related behaviors reduced-energy and behaviors vated-energy for ele a mechanism be may regions brain key use) in energy (i.e., concentrations abnormal lactate abnormal that possibility Ph.D., Michele Bertocci, Ph.D., Berndt, Andre treatment. addiction in to success a major to barrier block to relapse, atreatment lead may this that reasoning synapses, at key block changes can that mechanisms molecular Dr. to discover hopes Beaudoin synapse. excitatory at one specific changes cocaine of what the question addresses project This inputs. excitatory of the or some to all changes cause of abuse drugs whether unclear been it so has turn, in neurons, of number diverse by alarge are regulated neurons of dopamine activity The events. ing memories of to encode drug-tak structures brain diverse in synapses in changes to induce thought is release Dopamine neurons. dopamine on midbrain synapses to excitatory changes cause shown to havebeen abuse of drugs different Gerard Beaudoin, III, at Providence VA Center. Medical in-patient unit psychiatric the from recruited veterans to 60 given be will 12-months. and TMS outcomes 6- at 3-, suicide predict will correlation of this strength the that anticipates Further, she of risk. suicide severity with correlated be will changes these that and circuits fronto-striatal in connectivity functional alter will brain’s cortex the prefrontal dorsolateral Ph.D., Barredo, Jennifer Barredo hypothesizes that TMS modulation of activity in in of activity modulation TMS that hypothesizes Barredo intervention to prevent Dr. suicide. stimulation sive brain anoninva (TMS), stimulation magnetic to transcranial response symptom involved in circuits functional identify Therapies Next-Generation Basic Research Basic Research Basic

Ph.D., University of Washington, who is of who is University Washington, University of Pittsburgh, notes the notes the of University Pittsburgh, Brown University, Brown to seeks Trinity University, notes that ------non-TRS cases among the 3,942 study participants in an an in participants 3,942 study the among non-TRS cases and TRS to identify seeks team His (TRS). schizophrenia for treatment-resistant criteria meet thus and medicines or more to respond to antipsychotic two fail will phrenia schizo with diagnosed of notes 30% patients Downstate, to test its ability to reach targets in SCC. in targets to reach ability its to test imaging functional with concurrently performed be will TI To brain. the patients, in in tested be structures deep to reach stimulation neural for focal allows that technique a new (TI), interference temporal use will study clinical depression. This treatment-resistant in stimulation site brain for deep targeted frequently most the is which SCC, the in oflevel activity increased with associated been has Major disorder depressive (SCC) out of cortex reach. cingulate subgenual the as such targets deeper leaving regions, brain on superficial focused are TMS for as depression such treatments stimulation approved non-invasive currently brain notes that Canada, M.D., Venkat Bhat, disorder. bipolar onset pediatric with sion agroup of in adults depres and of mania feelings self-reported and connectivity activity/functional precuneus between relationship the play in concentrations lactate role that mediating the to test (MRSI) imaging spectroscopy resonance magnetic use will The team neural populations altered by cancer in the periphery, the in and by cancer altered populations neural discrete The is to hope identify growth. tumor during cuits cir these inhibit and to stimulate studies chemogenetic and optogenetic inform will This states. sleep/wake in changes and to one related another, growth, tumor temporally are changes how these and circuits neural discrete disrupt tumors how detailing map effector a brain construct is to aim The cancer. in disturbance sleep driving on mechanisms focusing is team the models, mouse Using impairments. cognitive and disorders mood to cancer-associated related intimately are which types, cancer many problems across sleep prevalent in Jeremy Borniger, Ph.D, studies. future in validated be could which for model TRS, prediction development of amultivariate future inform will hope results They enzymes. metabolism antipsychotic known encoding genes in variants common as well as of number variants, copy presence the phrenia, for schizo scores genome-wide risk and resistance treatment between association for test will they cases, TRS identified Among trees. decision on rule-based based of TRS dictions automated pre is validate study.to aim The clinical existing Ph.D., Bigdeli, Tim Therapies Next-Generation Research Basic Diagnostic Tools/Early Intervention Diagnostic New Technologies New

M.Sc., FRCPC, M.Sc., State University of New York, of University New State Stanford University, Stanford interested is University of University Toronto, - - - - -

bbrfoundation.org 11

------University of Maryland, University of will University of Texas Medical Texas Universityof Branch University of Wisconsin-Madison, University of Basic Research Basic Research Basic Research

tions between pre-adolescent SA risk and the emergence of explore the notion that theexplore notion inadequate in a brain development area called the ventromedial prefrontal cortex (vmPFC) affects abilitythe to integrate affective signalswith control functions, contributing the to emergence social of anxiety during(SA) adolescence. hypothesizes He that sufficient change in vmPFC connectivity strength will moderate rela opment of SA of and informopment the design developmentally of targetedappropriate, interventions. pared childbearing of 2%-4% to women non-pregnant of mouse model of revealed age.the condition team’s The that clinicallyTo test significanttheseideas, he SA symptomology. will collect fMRI data and longitudinal conduct analyses of functionalhow connectivity between vmPFC and affective/ regionscontrol changes during adolescence. Success might lead reconceptualizing to think we how the about devel Ph.D., Cahill, Michael studies which sleep disordered is character breathing (SDB), ized recurring by breathing cessations during sleep causing oxygenintermittent hundreds to up deprivation times of per pregnant as of women com night. is in present 15% SDB male, female, not but juvenile offspringmothersof subjected intermittent hypoxiato during pregnancy exhibit deficits inseveral autism-relevant behaviors. the team Now seeks determineto if the ability brain of cells called microglia to engage in synaptic pruning is selectively impaired in male, female, not offspring,but resulta as SBD—a of possible cause the of autism-related symptoms. They will also seekto restore microglial function in male offspring determine and the potential alleviation for pathology. of Shelly Buffington, Ph.D., Galveston,at noting recent evidencethat thegut microbiome can neurophysiology and regulate behavior and that a person’s offspring are gut acquiredmicrobiota seeks mother, from inthe this test to project a hypothesis concerning two mouse models called ASD, of the maternal high-fat diet (MHFD) and mater nal immune activation (MIA) models: that the ultimate insult driving social deficits a in bothcommonmodels onto converge team The pathway. also seeksdetermineto whether bacterial species they previously identified thatrestore social behavior in MHFD offspring alsorescue social behavior in MIAoffspring. This study has potentialthe identifyto cost-effectivenew, a treatment maternal for infection-induced mental health disorders and reveal underlying molecular and neurophysiological mechanisms mediating maternal obesity-induced neuropsy chiatric conditions. Ph.D., Buzzell, George ------Harvard Harvard University of Pennsylvania, University of is University of Washington, University notes of Basic Research Basic Research Basic Research Diagnostic Intervention Tools/Early

studying alterations how in the prefrontal area the of brain 50 individuals50 with clinically significant persecutoryideation carryto and engage with an integrated health mobile assess window the into dynamic They emergence PI. of willrecruit ment system month. ment one for Benjamin Buck, Ph.D., ered that in mutations called a gene novo de TRRAP can result with depression inmajor psychotic features, the team will perform experiments mice on with the TRRAP muta of schizophrenia of find to of geneslarge effect.Having discov Catherine Brownstein, Ph.D., M.P.H., seention in better to a patient understand results it how in with depression major psychotic features. They will analyze thebehaviors the of TRRAP mice and determine they how are different from unaffectedmice. They will also adminis a medication ter (Prozac) thatappears the major improve to anddepression psychosis in a TRAAP and patient, test for affects it how brain the behaviorand of the TRRAPmouse. negative symptoms captured in daily life using ambulatory assessment. willlink these imaging featuresmeasures to cognitive of and reward social anticipation, interaction process and emotion ing--core processes impaired in validate schizophrenia. To the importance prefrontal of stability as a unifying neural substrate manyof cognitive andnegative symptoms, they in everyday life, and are how impacted currently by pre give rise range a broad to negative of and cognitive symptoms in schizophrenia, they how relate expression to symptoms of Urs Andreas Braun, M.D., reciprocally, how manipulation how reciprocally, neural of firing can combat sleep/wake abnormalities and cancer itself. scribed antipsychotics. team The seeksprecise assessment theof stability and flexibilityprefrontalof activity patterns fourelicited by imaging tasks spanning working memory, ened—is static, not varies but in frequency and severity and involving different setsof contextualBuck factors.Dr. aims understandto factors maintain, that to, contribute exacer mitigate informbate, or to early PI, detection and interven his so, do team To outcomes. improve approaches to tion will technology in mobile recent developments invoke to make what possible they will hope be a real-time, real-place that persecutory ideation (PI)—the feeling experienced by many patients with psychosis that they are being threat University/Harvard Medical is School, examining the youngest children presenting with psychosis and symptoms 12 Young Investigator Grant Program 2019 a propensity to relapse, despite knowledge of likely adverse adverse of likely despite knowledge to relapse, a propensity show often disorder alcohol-use in drinking from abstain to who try those notes that Australia, Health, Mental and activity and decreases psychotic symptoms. psychotic decreases and activity network brain how CBD modulates to understand phrenia of model schizo amouse in and samples brain postmortem in approaches combination of a unique electrophysiological age lever will team The effects. antipsychotic to mediate system the endocannabinoid in molecules on specific how CBD acts Simon Chamberland, Ph.D., to depression. vulnerable peopleof identification FoxO1-related for possible early biomarkers test as signatures development and the sion and of behaviors; depressive levels FoxO1 between expres relationship causal the demonstrate for depression; vulnerability stress-related early-life the FoxO1 which mediate may through mechanisms molecular the hope to dissect colleagues and Dr. rodents, Cattane using Ph.D., Cattane, Nadia abstinence. extended following to relapse propensity the drives cortex anterior insular the that hypothesis the on manner, based acircuit-specific in relapse drives cortex about how anterior insular questions the unresolved address be to will Thefocus involved relapse. in circuits brain terize to model charac the to use is aim the behavior; this pitulate reca rats susceptible a rodent which developed in model has Dr. complications. Campbell health including consequences Ph.D., Campbell, Erin people. young of thousands many Development project involving (ABCD) Cognitive and Brain Adolescent NIMH’s longitudinal the in collected being data use will The research cognition. human underlying circuits and states latent brain dynamic to detect plans Dr. Cai this, To ADHD. with children control in accomplish cognitive in deficits with associated ganglia—circuits basal and cortex the connecting circuits dynamic by examining of ADHD models Weidong Cai,Ph.D, insults combine to raise risk of depression. In this study study of this depression. In risk combine to raise insults or environmental other involvement stress when early-life its suggesting up on research proteinits following product, gene FoxO1 the Italy, and Dio studying is Fatebenefratelli, antipsychotic agent. In this study he seeks to understand to understand he seeks study this In agent. antipsychotic an as (CBD) for use potential its cannabidiol and studying computational, and clinical dimensions to test theoretical theoretical to test dimensions clinical and computational, cognitive, involving amulti-componentdevelop framework

Therapies Next-Generation New Technologies New Basic Research Basic Basic Research Basic Research Basic Stanford University, Stanford to proposes Florey Institute of Neuroscience Florey Institute IRCCS Centro San Giovanni di di Giovanni San Centro IRCCS New York New University, is - - - - - is studying the mechanism of action of the rapidly acting acting rapidly of of the action mechanism the studying is it generates dramatic relief from depression symptoms in in depression from symptoms relief dramatic it generates when treatment, ketamine after minutes to hours first the pathway, involving ketamine in phase a poorly understood study will Ricagni Dr. Specifically, ketamine. antidepressant Ph.D., Ricagni, Chanaday Natali for of depression. treatment forms new developing for implications has research this Hence modified. be can themselves they because notes, Dr. Chan targets, treatment potential are marks major in depression. Methylation ways path contributes to disease and gene regulation impacts functionally how methylation DNA studies project This methylation. via genes our in registered be may aging and development, factors, psychosocial of effects the that suggests Evidence activation. their affect to DNA which tags molecular of of removal involve attachment the tion of genes—which regula epigenetic call scientists of what modes one of several it methylation, is Called or of expression, activity, genes. the modify routinely cells which through amechanism studying Ph.D., Chan, Robin Abnormalities in tactile perception are prevalent features in in features prevalent are perception tactile in Abnormalities development life. adult throughout and interaction social and role communication in born, it to play acritical continues are when infants modalities sensory developed most the Among Ph.D., Che, Alicia regions. brain relevant clinically four in dynamics circuit studying a primate, in regions decision-related brain in dynamics tion of circuit descrip to adetailed provide aims project orders. This dis neurological and psychiatric with for individuals interfaces brain–machine and of circuit-level therapeutics development for way pave the the could techniques, ing machine-learn and manipulation circuit fortools precise when combined with understanding, Adetailed sion-making. involved deci regions in brain subcortical and cortical in dynamics circuit neural University, to understand seeks Ph.D., Chandrasekaran, Chandramouli future. the in treatments efficient and for more even provide specific depression abasis and in effects beneficial ketamine’s underlying mechanisms lar the of molecu understanding increase could findings The effects. antidepressant resulting the with these correlating drug, the by affected neurons in signaling postsynaptic versus the roles of presynaptic dissect will The team patients. many fant interactions fundamental for early social development. social for early fundamental interactions fant to parent-in of touch contributes powerfully sense the that

Therapies Next-Generation New Technologies New Basic Research Basic Basic Research Basic Weill Cornell Medical College, notes College, Medical Weill Cornell

Virginia Commonwealth University, Commonwealth is Virginia Vanderbilt University, Boston ------

bbrfoundation.org 13 ------New York University, is University, New York University of California, University of Irvine, University Pennsylvania, of notes Basic Research Basic Research Basic Research

Diagnostic Intervention Tools/Early

that pregnant misuse who may women give birth opioids an to infant sufferingneonatal withdrawalfrom opioid syndrome to infants supplementation NOWS receive opioid (NOWS). taper withdrawal, which is associated with potential neurode cognitive impairments, delay, velopmental and psychiatricdis suchorders, as withdrawal anxiety. Non-opioid treatments are urgently needed. A critical first step novel developingin targets Gregory Corder, Ph.D., Gregory Corder, treatments is NOWS identify to for the specificbrain circuits that the molecular (MOR), receptor express target the mu-opioid of willCorder Dr. use opioids. imaging assess to the pathological activity dynamics in adolescent mice during modeling NOWS behavioral anxiety assays and will therapy test non-opioid a novel designed effectively to erase neurodevelopmental the pathology that primes NOWS of adolescents anxiety. for Ph.D., Emmanuel Cruz-Torres, regulating food motivation for and in disordersinvolved with disorderedreward processing including depression and addic does chronic How tion. intakepalatable of food alterspecific cell types and circuitsregulate to future feeding behavior? Thisresearch willidentify excitatory to inputs NActhe altered chronicby high-fat intake and establish modulation how of NAc and inputs neuronal subtypes regulate the intake and obtainmotivation to fatty nourishment. Colon-Perez,Luis Ph.D., seeks understand to substance use and disorders (SUD) addiction developing by and validating sensitive, predictive neuroinflammatory in vivo markers.proposed The studies, focusing developing morphine, early on involve clinical MRI imaging markers SUDs of and their relationship time over theto neuroinflammatoryprocess. MRI markers generated theseby studies and validated with methods determin of ing brain changes drug to due use could determine the level neuroinflammatoryof activity in patients and eventually the livesimprove those of with addictions. interested in brain non-neuronal cells called astrocytes that criticalplay in roles learning and the and possibil memory, ity that dysregulation astrocytic of metabolism is involved in neurodevelopmental disorders such as Angelman syn drome. Thisproject will investigateof role astrocytic the lactate metabolism memory formation in during long-term and its regulationdevelopment in Angelman Syndrome. willHe investigate whether astrocytic lactate metabolism is dysregulated young at and ages old using a well-established Angelman of model syndrome. mouse ------Stanford University, observes Stanford University, University of Denver, notes that notes Denver, University of Washington University School of Washington University School of Basic Research Basic Research Basic Research

Medicine, is focusing two on genes associated with schizo bothphrenia, affecting and Pde4b, Disc1 activitythe of the enzyme In addition the to phosphodiesterase 4B (PDE4B). genetic evidence, have effects PDE4 inhibitors of depreson This cognition, project and will memory. sion, explore the hypothesisthat schizophrenia associated with dis PDE4B brain’s nucleus accumbens nucleus a primarybrain’s (NAc), circuitry of hub have a co-morbid substancehave a co-morbid will use He disorder. the explore possibility that there is a common neurobiological mecha Daniel Christoffel, Ph.D., that in patients with binge eating eating disorder, behavior is accompaniedfeelings by shame, of disgust, and desirea but inability binging; stop to and that almost a third patients of nism, proceeding from the theory that the neural circuits that regulate obtain motivation to food are broadly similar thoseto “hijacked” drugs by abuse. of will He focus the on study ADHD of and learning disorders. tive control performancetive control in children a sample of years (8–12 withold) and ADHD without from an ongoing government has advantages and disadvantages performance for outcomes. team The will characterizemotivational modulation of cogni vation on cognitivevation on performance control within a theoretical framework called Dual Mechanisms which Control, char of acterizes cognitive in terms control temporally of distinct, proactive, and reactive mechanisms, control each which of investigationsreward of incentives cognitive on performance in ADHD have yielded mixed results. Chiew Dr. aims to clarify this issue investigating by the effectsrewardof moti Kimberly Ph.D., Chiew, how PDE4B alters these PDE4B how features is critical gaining to insight schizophrenia.into tion, Dr. Chen proceeds Chen the Dr. on thesistion, that understanding ruption may ruption result from misinterpretation neuromodulator of signals. Noting that the spatial, temporal, and amplitude characteristics intracellular of signals are among the most importantfeatures thatdetermine neuromodulator func Yao Chen, Ph.D., Yao provide insightsprovide emerging into circuitsthat integrate primary sensory processing and cognitive higher-order features such as social behaviors. Thesecircuits, proposes,convergent she key a could understandingto hold the commonalityamong the seemingly behavioral independent symptoms autism of spectrum disorder. individuals with exacerbating ASD, the core social deficits. aims Che Dr. understand to social how features are encoded alongside early tactile sensory inputs—information that can 14 Young Investigator Grant Program 2019 the nucleus accumbens (NAc), known to play an important important to play an (NAc), known nucleus accumbens the in activity record (i.e.,will self-control). display The team reward-seeking from or refrain ited aversive by stimulus the inhib be to fail mice themonitor if will The team evoked. is conflict time, same at the stimuli of these to both exposed are mice When punishment. amild predicts that stimulus a induce he will a reward, animals the earns that a task teaching to do so. After fail when they happens what and self-control, purposes)—exert for research viduals—(mice, when indi brain the in happens what study Berkeley, will Johannes de Jong, Ph.D., Jong, de Johannes some or way. in other brain, the across generally pruning axonal mutations affect C4 whether learn to seeks research This schizophrenia. and pruning aberrant between link causal time a potential first the for offers and mice, of system visual the in refinementconnections of the affect to shown been has C4 encodes that gene The nia. of schizophre risk at increased complement are C4 factor called of amolecule variants genetic certain people carrying that found study Arecent prior to birth. connections aptic syn removes excess brain the by which process the pruning, axonal Laboratory, Biology Germany, studying is Molecular Senthilkumar Ph.D., Deivasigamani, in remission. those and controls that of healthy from different it if is determine depression and with participants in phages macro and of monocytes profile activation of the acterize body. the throughout found char The is to hope cells lineage monocyte-macrophage of depression, specifically, tenance development main the in and system immune adaptive and possible role the innate of the regarding theories pursuing is major a episode. He depressive suffering patients in of cells subsets different the on detecting focus will Argentina, Aires, Daray,Federico M.D., patients. psychosis of asample in tool on the apilot basis intention to try is The exposure. stress following immediately samples marker bio stress to collect to prompt ability individuals the with measurement stress active and passive combines tool that app to produce Mind a smartphone-based Urban the modify will project, they this In wellbeing. on mental exposure) crime environment (e.g.,and urban of living the impact city the to assess designed is team by the app developed Mind environment. The Urban natural the in to stress exposure capture to accurately devices wearable apps and smartphone use Dr. will Cullen schizophrenia. as such disorders chotic to psy stress contribution the of in psychosocial interested Ph.D., Cullen, Alexis

New Technologies New Basic Research Basic Research Basic

Ph.D., M.Sc., M.Sc., Ph.D., King’s College London, UK, is London, UK, King’s College University of California, of University California, University ofUniversity Buenos European European ------the NAc, data that can inform new treatment approaches. treatment new inform can that data NAc, the of sub-areas different within self-control underlying circuits of description the contribute to adetailed will experiments and other This seeking. reward and selection role action in behavioral function of mPFC circuits. of mPFC circuits. function behavioral and connectivity on the of stress impact the analyzing development, during plastic are that nodes mPFC circuit to reveal mice engineered with experiments perform will Dr. DeNardo circuits, memory adult and infant between To relationship adults. in behaviors causal elucidate the maladaptive to produce stressors early-life by modified are and form circuits of how prefrontal understanding a mechanistic seeks Her team changes. behavioral term into long- adversity early involved translating in are likely and insults, to early-life (mPFC) vulnerable uniquely are cortex prefrontal medial the in circuits notes that Angeles, of the biological basis of suicide risk yet only a fraction of a fraction only yet of risk suicide basis biological of the improved understanding our have greatly studies genetic during adolescence. during dysregulation system to dopamine individuals predispose that of mechanisms discovery the inform could experiments sex-, These age-, manner. or an puberty-dependent in changes drugs to these sensitivity whether testing release, dopamine D2 regulate receptors target that antipsychotics including how drugs examine and transmission dopamine striatal in changes age-dependent are there whether determine will team Her mice. in transition juvenile-to-adult the across tissue brain striatal in and reuptake diffusion release, dopamine to visualize nanosensor) catecholamine infrared (near nIRCat called sensor fluorescent developed dopamine a newly use will Ph.D., Delevich, Kristen genetic variation influencing suicide risk has been accounted accounted been has risk suicide influencing variation genetic Ph.D., DiBlasi, Emily PTSD. without sex-matched to 10 responders and compared PTSD age- with of 10 asubset using WorldPTSD Trade Center responders chronic in evident is neuroinflammation extent to what gate investi will The team imaging. MRI via obtained signatures and brain symptoms, PTSD chronic neuroinflammation, between relationship the PTSD. Dr. hope Deri to examine some in people with symptoms behavioral the and pus hippocam the in levels cytokine pro-inflammatory both reduced has drugs anti-inflammatory non-steroidal ment with Yael Ph.D, Deri, Laura DeNardo, Ph.D.,

New Technologies New Basic Research Research Basic Basic Research Basic Research Basic Stony Brook University, treat notes that University of Utah, observes that that observes of University Utah, University of California, Berkeley, of University California, University of California, Los Los of University California, - - -

bbrfoundation.org 15 - - - Emory University, will Emory test University, Erasmus University Medical Cold Spring Harbor Laboratory, University of California University of San Diego, Basic Research Basic Research

Next-Generation Therapies

will test the hypothesis that aspects social of anxiety are mediated stress-induced by changes in a brain region called locus coeruleusLC is (LC). a small, deep-brain area, and serves primary as the brain’s source the of neurotransmitter noradrenaline.locus The coeruleus-noradrenaline system Claudia Espinosa-Garcia,Ph.D., the hypothesis that high levels stress of suppress autophagy in microglia, leading excessive to brain inflammation associated withdepressive-like Autophagy behavior. is anessential process in which damaged cells dysfunctional remove components. eating and therapies disorder, like cognitive behavior therapy strong on depend executive function be to successful. Dr. method will be evaluatedEichen’s ability its patients for in 32 reduceto binge eating in provided when addition the to current gold-standard treatment. novel executive The func trainingtion will be adapted from a compensatory cognitive training program that has successfully executive improved function in patients with several psychiatric disorders and significant cognitive impairments. Hanan El Marroun, Ph.D., term effectsprenatalof cannabis exposure—the firsthit—and substance use in adolescenceand other stressors—the second hit—on neurodevelopmental trajectories brain of structure and connectivity. RomanDvorkin, Ph.D., (LC-NA) has a well established in arousal role and attention, and is believedbe to an important regulatorsocial of behavior. is alsoIt the of principal one brain systems activated during stress.team The willrecord and manipulate activity in LC neurons in female mice following adolescent social isolation, research that may the elucidate interaction social of stress with social motivation and social memory signaling in LC and form the basis a better of understanding the of unique neural circuit mechanisms social of anxiety. Eichen, Ph.D., Dawn tion for people who have binge who eating people for tion disorder a mood plus anxietyor Executive disorder. function is impaired in binge will develop and test a method training of executive func Center, Netherlands,Center, is testing hypothesis” “double-hit a that exposure substances to during pregnancy may lead to subtle alterations in brain making development the child vulnerable stressors to which lead them begin to using sub stances. This study will use a large population cohort in the Netherlands, in which the Generation children R study, and their parents have been from followed early pregnancy onward. Neuroimaging will be used examine to the long------Michigan State Ph.D.,

Interdisciplinary Institute for University of Oregon, notes that notes Oregon, University of Basic Research Basic Research Basic Research

Next-Generation Therapies

Neuroscience - CNRS Bordeaux, / University of France, is studying the mechanisms through which ketamine exerts antidepressantrapid effects. Ketamine is to engageknown a neurotransmitter called receptor the receptor NMDA (NMDAR), which is a vital actor in brain and development functioning. the binding how ketamine of However, the to by early-life adversity, a major risk depressive dis a major major for early-lifeby adversity, suggesting MCs are epigenetically permanently, programmed activated in response psychological to stress, release a myriad mediatorsof that can initiate, amplify, inflam and prolong andmation, are distributed including throughout the body, the brain. This project willproceed prior experiments from in a sex-specific order, fashion. stress initiates persistent inflammatoryresponses leading to will She depression. study mast of the role cells in (MCs) early-life adversity programming adult vulnerability of to depression-like symptoms and behaviors. MCs are highly Natalia Duque-Wilckens, D.V.M, wants mechanisms about know to more University, which by nologies to explore with explore if to nologies unprecedented and resolution how ketamine changes the locationNMDARs of the on surface neurons,of perhaps restore brain to functions. NMDAR can translate antidepressant into action well is not tackleunderstood. this To challenging the question, team will use new high-resolution single-molecule imaging tech sis are correlated This with over-segmentation. will lay the Julien Dupuis, Ph.D., groundwork for developing a domain-general for groundwork framework by which understand to the mechanisms underlying symptoms psychosis. of common in psychosis. This project will use a large-scaleonline trial the to hypothesis that positive symptoms psycho of Sarah Ph.D., DuBrow, canwe make false attributions, such as overgeneralizing out situationcomes many to from one or (under-segmenting) attributing each new cause a completely to event (over-seg recent, very large resource control structural 10,000 over for variants matched ancestry. for for. This project for. willtest hypothesis the that rare structural variantsrisk to suicide death of contribute using the large and unique genetic dataset and resources available in the Utah Suicide ResearchStudy comparing(USRS), these data a to menting). Deficits in “latent cause inference” are thought in be misperceptions to involved some by and false beliefs 16 Young Investigator Grant Program 2019 of the results in search of potential biomarkers. biomarkers. of potential search in results of the analysis conduct extensive then and inhibition for behavioral infants evaluate 12 At at 4months. she will months, infants in function and structure brain temperament, to examine task detection a novelty during electroencephalography and imaging, resonance magnetic of reactivity, assessments ioral conduct Dr.behav inhibition. Filippi will behavioral and reactivity negative to both central is and infancy in emerges network salience and development amygdala of the aberrant that is The developmenthypothesis the ofpredict anxiety. that inhibition—temperaments behavioral and reactivity negative predict that infancy in networks for brain search will project This life. in early very disorders for anxiety risk reveal that biomarkers to identify seeks NIH, Sciences, Health Ph.D., Filippi, Courtney functional connectivity. altered with individuals in memory working improve spatial can manipulation this hope that is His involved learning. in processes enhance to potentially beams light using cells pal hippocam to stimulate optogenetics use also He will circuits. neural relevant certain understand to better learning during recordings electrophysiological high-density perform will He deficits. cognitive and alterations these captures that model a with mouse works Dr.deficits. Fernandez-Ruiz to memory related be may formation, which hippocampal the and cortex prefrontal the between connectivity functional altered is patients schizophrenia in symptom akey notes that Ph.D., Fernandez-Ruiz, Antonio time. first for the humans in systematically performed to be tracing lineage allow will that TAPESTRY called atechnology to develop seeks research This tree. family their by about studying aperson learning It much like is create. they structures brain and types cell which to watch progeny their all and cells those to track researchers allowing develops, brain the as proteins or special viruses with labeled are cells tracing, lineage In humans. in not performed be could tool of biology, tracing, developmental central lineage a because is This studies. on animal development based is about brain much we know of what that observes Medicine, M.D., Evrony, Gilad rodents. in conducted be will This work microglia. in autophagy stimulate to effects, antidepressant aneurosteroid with of allopregnanolone, ness effective therapeutic the evaluate also It will microglia. in autophagy compromises stress if to determine seeks research This brain. the in non-neuronal cells important are Microglia

Diagnostic Tools/Early Intervention Diagnostic New Technologies New Basic Research Basic Basic Research Basic Ph.D., Ph.D., National Institute of Environmental of Environmental Institute National New YorkNew of School University New York New University, - - - NIH, notes that people with depression are more likely to more depression likely are people with notes that NIH, Kyle Ph.D., Flippo, for depression. value or prognostic test,” diagnostic with “stress or psychiatric challenge, neuroimaging standardized a toward steps first the to take as well as stimuli, social uous to complex, responds ambig of how brain the understanding better is goal The stimuli. by ambiguous evoked activity brain of patterns spatiotemporal in of heterogeneity characterization allowing individuals, depressed and healthy both in study fMRI conduct an Dr. will Finn depressed. become trait this pronounced most version the of with those only which in on a spectrum ferent people respond differently—perhaps But dif social. is stimulus when the especially negative, as stimuli to neutral interpret and information to negative attend Ph.D., Finn, Emily two cortical areas will modulate activity in a third, called the the called a third, in activity modulate will areas cortical two rTMS, in that stimulation, aform of non-invasive brain evidence to provide seeks study This schizophrenia. tion in dysfunc of cognitive mechanisms neural the regarding edge Michael Francis, M.D., of shock. threat under and context athreat-free—safe— of interest: contexts two under adigms par processing reward completing while fMRI undergo will 45 and with without PTP individuals so, 45 trauma-exposed To function. do circuitry and processing information lated reward-re disrupts and behavior reward-processing influences abnormally and maladaptively PTP in reactivity threat that hypothesis the test (PTP).He will psychopathology trauma post- with individuals in of affect positive expression and responsible generation, for maintenance, the tion-processing informa and reward-related behavioral, brain, influences to threat how reaction to understand seeks Texas at Austin, Fonzo,Ph.D., Gregory brain. to the signaling through consumption alcohol FGF21how inhibits to determine neuron activity observe will and populations, cell specific manipulate to aims research accumbens). This (nucleus project NAc to the and amygdala) of the (part BLA consumption may be excitatory neurons which reside in the the in reside which neurons excitatory be may consumption alcohol regulates of that FGF21 brain the target in direct the Dr. Flippo hypothesizes studies. mouse in consumption alcohol reduce to shown significantly been has it effects; 21 factor (FGF21),growth for potent its metabolic known hormone endocrine the fibroblast in interested is Clinics, impaired in schizophrenia, due in part to a gap in knowl in to agap part due in schizophrenia, in impaired control (CC), commonly of cognitive impairment aprocess for treatments no effective are there notes that Medicine, Diagnostic Tools/Early Intervention Diagnostic

Basic Research Basic Research Basic National Institute of Mental Health, Health, of Mental Institute National University of and University Iowa Hospitals Dell Medical School, of University Medical Dell Indiana University School of School University Indiana ------

bbrfoundation.org 17

------Yale University School of University School of Yale Sorbonne University, France, University, Sorbonne University of Chicago, University of that notes Stanford University, is pursuing Stanford University, Basic Research Basic Research Basic Research Basic Research

clues that cortex the orbitofrontal may a central play in role Medicine, seeks dissect to the molecular basis PTSD of measuringby the activity genes of in particular cell types. Because are women twice as likely as develop PTSD to men tional effort selectivefrom attention and characterize the underlyingcircuitry and neuronal processing that support these distinct processes. Through experiments withrhesus monkeys and analysiswith models, the computer aim is identify to neural substratesin the primate brain that are critical attentional to effort how contextual and attributes influenceits transitions.Mechanistic insights may expedite individuals with ADHD commonly suffer deficits from in selective maintaining attention, prolonged over attention periods, and flexibly switching tasks.proposes Ghosh a Dr. new conceptual experimental framework delineate to atten tions between a threat and a physical location, yet little is tional memories. identifying the molecular determinants PTSD of pathology. Another part the aims of project unravelto specificmolecular differences between subjects with PTSD and those that are comorbid for PTSD and major depression. Felicity Gore, Ph.D., seeksdefine to how the hippocampus and the amygdala coor dinate their activity during sleep sustain to the formation of in memories normalaversive and pathological conditions. Those brain two regions required are to establish associa known the about the physiology of interactions. In optogen tically manipulated rats will she study emotional of the role memory in differentphases sleep and their associated oscilla torybrain-wave activities. post-traumatic model of rodent A stress disorder will (PTSD) be used investigate to these how consolidation processes are disturbed in pathological emo Matthew Girgneti, Ph.D., deems criticalhe it determine to the molecular characteristics that differentiate females malesfrom with PTSD and will therefore analyze RNA cells of output from postmortem cor tical tissue from females with PTSD and matched controls, generating single cell-type transcriptomic profilesto aid in portion the of GABA-A receptor—has therapeuticpotential in FXS other neurological or disorders. Supriya Ghosh, Ph.D., effortsto better classify ADHD and provide mightpotential targets.therapeutic Gabrielle Girardeau, Ph.D.,

------University of Toronto, Canada, Toronto, University of Texas Tech University Health Tech Texas University of California, University of Irvine,

Basic Research New Technologies Diagnostic Intervention Tools/Early

Next-Generation Therapies Sciences Center, is interestedSciences inmicroglia, Center, pathogen-eating macrophages in the brain that integrate stress-induced neu roimmune signals leading behavioral to consequences. This willproject study neuron-microglia interactions. These are modulated several by molecular and cellular pathways, dys regulation which of can have neurobiological consequences. these at look Gadad interactions Dr. seeksTo molecular andfunctional characterization neuron-microglial-spe of cific markers.utilizingBy bioengineering novel a method, of a receptor for the for a receptor inhibitoryof neurotransmitter GABA is a drugpossible target. Thisproject, using an animalmodelof FXS, will test if a potential drug Genaro’s developed in Dr. lab—a so-called allosteric (positive PAM a of modulator) studiesFragile syndromeX (FXS), neurodevelopmentala dis causedorder silence the by of FMR1 and gene deficiency a of Fragilemental X retardation (FMRP). component A protein Karina Genaro, Ph.D., will also examine can if supplementation exercise omega-3 or havea positive impact markers upon gut of barrierintegrity inflammation. and mine if adults with have increased depression levels blood of associatedproteins (biomarkers) with gut barrier function, and if these are associated with markers inflammation; of thenwill he determine if these markers are associated with severity depressivesymptoms of and cognitive function. He barrier, resultingbarrier, in increased exposure gut to microbes, which maystimulate inflammation. Usingblood samples a from study patients with of heart disease, Gallagher Dr. will deter ciated with persistent depressive symptoms, reduced response antidepressantto treatment, andincreased risk dementia.of may be reduced contributor integrity possible One the of gut wants better to understand the relation between persistent inflammation and cognitive impairment depression. in Inflammation can exacerbate cognitivedeficits, and is asso Damien Gallagher, M.D., Damien Gallagher, neurons and microglia will beco-cultured from postmortem brains understand to diffusing of the role factors to thought inbe dysfunction. involved brains The studied will be from suffered who people depression. major from Bharathi Gadad, Ph.D., ACC, as well as connectivity between thesethree CC-relevant structures. The centralhypotheses rTMS will are resultthat in increased functional activation in and the lead ACC to increasedto functional connectivitybetween the three cortical areas. 18 Young Investigator Grant Program 2019 involve scanning 10 adolescents and/or young adults with 10 with and/or adults young adolescents involve scanning will disorder. bipolar This in switches mood in implicated previously circuits neural functional in son-level fluctuations per assess will Her team patients. individual in switch mood to predict useful be to specificity and sensitivity adequate with markers brain-based energy. and mood She in seeks tuations fluc by dramatic characterized is disorder bipolar notes that Ph.D., M.D., Hafeman, Danella group. disorder bipolar high-risk the in to college transition the during difficulties functioning and symptoms clinical to predicting responses behavioral and neural reward-related of utility clinical prospective potential the investigate and for disorder; low bipolar risk versus at high adults emerging in regulation and emotion positive reactivity increased lying under mechanisms behavioral and neural the investigate will She to college. transition the during freshmen college among sample adult anot-yet-diagnosed in emerging risk disorder of bipolar markers examine disorder. bipolar Hereing she will for develop at risk of individuals detection and diagnosis rate accu in aid may that processes pathophysiological to identify June Gruber, Ph.D., effects. anxiolytic respond to ketamine’s successfully may individuals which predicting biomarkers by identifying research clinical inform could This state. anxious elicit an to paradigm aversive events unpredictable and predictable of threat the and sequence aresting-state involving visits study complete two will participants Healthy of anxiety. markers behavioral and on neural of ketamine acute impact the adouble-blind to measure procedure use He will threat. unpredictable to an response startle increased the attenuate will and cortex prefrontal medial and hippocampus the between of connectivity a type reduce will application amine ket acute that hypothesis the test He will of anxiety. markers andbehavioral neural reduce agents anxiolytic effective that is theory central His anxiety. and of threat processing the to relevant circuits of neural function the to understand manipulations pharmacological and experimental uses NIH, Ph.D., Gorka, Adam rats. in decision-making value-based to mediate regions brain downstream with interacts orbitofrontalthe cortex on how focuses study depression. This and nervosa, anorexia addiction, including disorders psychiatric in disrupted is process this as critical, is computed executed and are decisions how value-based Determining choice. to compute execute and regions brain other with interacts how orbitofrontal the cortex understand to better She seeks decision-making. value-based Diagnostic Tools/Early Intervention Diagnostic Tools/Early Intervention Diagnostic Therapies Next-Generation Basic Research Research Basic University of University Colorado, Boulder, wants National Institute of Mental Health, Health, of Mental Institute National University of Pittsburgh, ofUniversity Pittsburgh, ------exhibit a number of overlapping behavioral symptomolo a number of overlappingexhibit behavioral addiction and major depression, OCD,that schizophrenia, Each scan will provide enough data to build aperson-level to build data provide enough will scan Each mood/energy. in by changes triggered to 9months, weeks over of 6 aperiod times four disorder bipolar symptomatic 25CN-NBOH and lisuride. LSD, agonists: 5-HT2AR other of three to that psilocybin brain’s the to compare response will Dr. Hansen primates, In non-human effects. treatment observed for the necessary is experience hallucinogenic the if It not is disorders. known psychiatric other not major only but depression disorder also in potential treatment for their investigated being currently is ketamine, drug the like Psilocybin, receptor (5-HT2AR). 2A theserotonin to by binding effect itspsychedelic mediates that drug anon-selective is Psilocybin brain. on the bin acts psilocy about how drug the to learn Hospital, seeks General Hanne Ph.D., Hansen, energy. and mood in changes with track these if and individuals healthy than networks brain functional in show patients more disorder bipolar fluctuations symptomatic if reveal in may mood/energy. This fluctuations with tracked be will which in changes portrait, connectomic accumbens and thalamus. thalamus. and accumbens nucleus cortex, the connecting circuits of specific regulation in synaptic PrLalterations pathway-specific and cell- assess to rodents with performed be will experiments Behavioral flexibility. cognitive including functions, high-order encode that cortex prefrontal prelimbic (PrL) region medial of the the in circuits on focuses project This stress. chronic ceived or self-per psychosocial chronic with individuals in observed also are that performance, cognitive impaired including gies, Ph.D., Hearing, Matthew disorders. other for and bipolar treatment and intervention improved support early could This works. emotion control net and cognitive between neuroplasticity structural of evidence to providesubsequently quantifiable and disorder bipolar with individuals in emotion networks control of cognitive in disconnectivity structural identify to Dr. Haut seeks tracts, matter white of large integrity the via connectivity structural quantifies which (DTI), imaging tensor behavior. diffusion Using disinhibited and states, mood lability, extreme emotional of disorder, bipolar including symptoms to key controlnitive of fundamental emotion are cog underlying network neural the in disruptions notes that Ph.D., Haut, Kristen Diagnostic Tools/Early Intervention Diagnostic Therapies Next-Generation Basic Research Basic Research Basic Rush University Medical College, College, Medical University Rush Harvard University/Massachusetts University/Massachusetts Harvard Marquette University, notes Marquette - - - - - bbrfoundation.org 19

------Feinstein Institute for Ph.D.,

Northwestern is inter University, Child Mind Institute, is studying Basic Research Basic Research Basic Research

Diagnostic Intervention Tools/Early tational framework assess to whole-brain semantic space in individuals with ASD based fMRI on data gathered while affected individuals17 watchmovie.The a aimsagedto 5 are discoverto which brain areas display different extent and magnitude functional of activation given to stimuli, hypothesesable in clinical populations, this seeks project a definitivemore understanding of orbitofrontal of the role the andcortex dopamine (OFC) in model-based identity learn ing in healthy subjects. Accordingly, the team will test for causal and dopamine OFC for roles in identity prediction signalingerror in humans. Suk Jun Hong, Ph.D., brain mechanisms underlyingabnormal perceptual process ing and their relationship high-order to cognitive deficits in individualsseeks Hong with compu a develop to Dr. ASD. andwhether these alterations are related perceptual to status in ASD; whether patterns semantic of space in ASD reveal subtypes; and whether the semantic brain map predicts Ph.D., Howard, James rewards. Aberrant functionality within the midbrain circuit composed dopamine of neurons hasnegative a profound in impactschizophrenia motivated behavior, on among other conditions. His recent research raised the possibility that symptoms schizophreniasome of are related abnormal to rewardidentity prediction generate test signaling. error To tory and somatosensory stimuli. neutral Some stimuli may seem threatening,leading the to intensification of perception andencoding traumatic of Hoffman Dr. memories. willtest this hypothesis using auditory fear conditioning in rodents. PhilippHoman, M.D., Medical Research/Northwell Health, seeks discover to prog individualnostic biomarkers improve to treatment decisions inpatients with schizophreniaand otherpsychotic disorders. hasHe been studying a candidate marker called the striatal connectivity index, which captures the connectivity between the striatum and the cortex, differentiate to responders poor from robustresponders antipsychotic to treatment. All anti psychotics act receptors in on the striatum. there is However, strongevidence that the biomarker mightalso be sensitive to the effectslorazepam,of a short-acting benzodiazepine that is widely used in the treatment psychosis. of This project will thus systematically study the effectslorazepamof on the striatal connectivity index. clinical symptoms. ested in prediction signals, error which the is brain how thecomputes difference between expected and experienced ------University of Minnesota,University of Ph.D., Pennsylvania State University, University of NorthUniversity of Carolina at University of California, University of Los Diagnostic Intervention Tools/Early Next-Generation Therapies Next-Generation Therapies injury. Alterationsinjury. in these connections may affect sensory processing after TBI and result in altered audi perception of traumatic brain injury that notes She (TBI). connectivity between sensory and emotional neural networks is highly conserved across species and is vulnerable traumatic to brain Ann Hoffman, Ph.D., Angeles, aims inform to translational research the on under lying contributing mechanisms post-traumatic of stress after suring neurobiological changes during treatment recovery. Hobkirk willDr. test the feasibility using of saliva analysis measureto dynamic neurobiological information through the expression non-coding of genetic markers. This project will measure changes in salivary microRNA expression and brain function while reduce smokers their dependence on nicotine with very cigarettes. low-nicotine brain mechanisms in involved reward and inhibitory control brain circuitry predictive sustained of recovery substance for users.fMRI But is too expensive use to with all patients intreatment real-world settings.This project addresses the critical inexpensive need for methods non-invasive mea of Andrea Hobkirk, Ph.D., Hobkirk, Andrea thatnotes fMRI scans are beginning functional elucidate to and assist therapeutics novel of in the based development on the targeted actions psilocybin of in relevant brain regions. ioral consequencespsilocybin/psilocin of exposure. This will inform assessment potential of therapeutic use psilocybin of cantly reduce anxiety clinical and in depression multiple trials.Herman will Dr. use wild-typeand 5-HT2A trans genic mice examine to the cellular and circuit effectsof the active metabolite psilocin in the central amygdala and the 5-HT2A of role receptors in that brain area in the behav drug psilocybin, which has recently been shown signifi to Melissa Herman, Ph.D., Herman, Melissa actions and brain region-specific effectsof the hallucinogenic cortex will facilitate working memory-based decision making. Alexander Herman, M.D., Herman, Alexander is studying cognitive and control the importance cogni of tive effort: volitional the allocationof cognitiveresources during challenging tasks decisions. or His team is working develop newto interventions that directly augment cogni tiveeffort, withideasreference to in cognitiveneuroscience and neuroeconomics that have recently demonstrated that cognitive impairments control-related in addiction result in part from the over-discounting and diminishment cogni of tive effort. This research will test the hypothesis in human subjects that microstimulation the of dorsolateral prefrontal Chapel Hill, aims better to understand underlying cellular 20 Young Investigator Grant Program 2019 studies have shown peripheral measures of inflammation to of inflammation measures peripheral shown have studies in-vivo activation; astroglial reduced paradoxically, and activation microglial of BD show patients increased tissue disorder. bipolar Postmortem brain in target therapeutic tial Muhammad Husain, M.B.B.S, contributors to depression. causal early understanding for work may possibilities open up This tissue. brain harvested analyze and response, affect elicit anegative to designed atask during activity monitor brain regions, their five brain in electrodes microwire with mice implant she will To vulnerability. to the contributing do this, mechanisms molecular and cellular the to identify measure vulnerability theneural-circuit on based profiling molecular specific, type conduct genome-wide, cell- will Dr. Hultman research this In measures. (EEG) to electroencephalogram similar are which recordings, potential field on local based is measure This stress. chronic following showlater behaviors depressive will animals which predicts reliably that a novel measure identified she has a rodent of model which depression in Ph.D., Hultman, Rainbo symptoms. depressive develop eventually will who those for identifying markers biological specific provide as well for depression, as risk of intergenerational substrate the neural elucidateis to aim without it. The overall (aged 14 those and to 16) major disorder depressive with adolescents in structure and function brain compares that Project grant Connectome Human ongoing to an add will The project risk. with associated specifically factors mental neurodevelop adolescent to understand and adolescence; in development the to of predict symptoms depressive learning machine and imaging brain Technology, multimodal use will Ph.D., Hubbard, Nicholas populations. on European mainly focusing studies previous in missed been have that factors genetic additional reveal may and populations applicable across is factor genetic schizophrenia into howcritical a insights provide will This controls. 100 and healthy cases 100sequencing schizophrenia by populations, Asian East in relationship this now study Dr. will populations. Huang of European genomein scans schizophrenia with associations genetic site strongest of the the locus—is MHC the encoded—called are proteins MHC genome The where location risk. schizophrenia and (MHC) complex major histocompatibility the in variations genetic between possible relation the studying Hospital, is General Ph.D., Huang, Hailiang is following evidence identifying inflammation as a potenas a inflammation identifying evidence following is Toronto/Centre Canada, Health, Mental and for Addiction Tools/Early Intervention Diagnostic Basic Research Basic Research Basic Harvard University/Massachusetts University/Massachusetts Harvard University of Iowa, has developed developed of has University Iowa, Massachusetts Institute of Institute Massachusetts

M.D., M.D., University ofUniversity - - and data from 40 controls. controls. 40 from data and includepatients 20 will trial The trials. for clinical markers surrogate and identify studies postmortem of findings the extend disorder to with bipolar patients in roinflammation neu to evaluate tomography positron emission (PET) use will study disorder. bipolar This with patients in elevated be Massachusetts General Hospital, is interested in “theory “theory in interested Hospital, is General Massachusetts disorders including FXS. FXS. including disorders of neurodevelopmental pathophysiology the to understand provide aframework could amechanism Such weakening. and potentiation synaptic local coordinates that mechanism unifying a may reveal experiments The of model FXS. mouse alteredin a is synapses inhibitory and excitatory modifies that plasticity synaptic coordinated locally whether test will project This impairment. cognitive and disabilities learning problems of developmental including arange causes that disorder autism-related an to FXS, lead tion protein (FMRP) retarda Xmental fragile for the gene encoding FMR1 of the Mutations (FXS). Technology, X syndrome Fragile studying is Ph.D., Ip, Pak Kan Jacque procedure to test specific hypotheses about whether and about whether hypotheses specific to test procedure neurosurgical awake aplanned during humans in niques tech recording single-neuron use will Dr.mind. Jamali of of biology theory underlying the to reveal project seeks ASD. This of most all, perhaps and order, schizophrenia, dis bipolar as such disorders behavior social in observed role deficits in play possible acritical may ability this make that processes cognitive of Disruption the of age. at 9to 11 maturity years development, reaching human during early forms one’scapacity than This own. beliefs different have may others that recognize and or desires thoughts, another’s to infer beliefs, of mind”: capacity the Ph.D., M.D., Jamali, Mohsen behavior. and states brain of anxiogenic processing the during cortex prefrontal the arole plays controlling in claustrum the that predicts Jackson Dr. cortex, prefrontal control the powerfully and to rapidly team’s on his ability Based claustrum. the called region brain a from arises which cortex, prefrontal inputs to the largest on one of focus the He will anxiety. generating in pathways more to input know role about the Dr. of wants these Jackson and regions, brain inputs other long-range from receives also behavior. Yet cortex prefrontal the anxiety-related and stress to modulate (HPA) axis adrenal hypothalamic-pituitary- the in control activity cortex outputs prefrontal ofthe the to decipher how efforts extensive made have researchers that Ph.D., Jackson, Jesse

Basic Research Basic Basic Research Basic Research Basic University of Alberta, Canada, notes notes Canada, of University Alberta, Massachusetts Institute Massachusetts of Harvard University/ Harvard - - - - bbrfoundation.org 21 ------Institute Psychiatricof Weill Cornell Weill Medical Ph.D.,

Stanford University, states Stanford that University, depres University of Illinois University of Chicago, at observes Basic Research Basic Research New Technologies

Next-Generation Therapies College, seeks discover to mechanisms circuit-level linking oxidative stress and behavioral depression-induced change. shipmitochondrial to oxidative stress, and make possible evaluation whether of similar mechanisms may be involved in conventional chronic stress models, thus perhaps also revealing new targets treatments for depression. for Lana Ph.D., Kambeitz-Ilankovic, University and Hospital, Phenomics Genomics (IPPG), seeksLMU, Germany, establish to “neuro-cognitive preci that acute hunger can be driven the by activation a sub of neurons in of group the arcuate the of nucleus hypothalamus that express Agouti-related peptide (AgRP). postulates She that AgRP neurons are a good candidate the for explore to effective of development treatmentsto suppress drug craving in addicted individuals. This project seeks determineto the effect of AgRPneuronal excitability on drug-seeking behav Jung, using Dr. zebrafishior. larvae as an animal model, seeks understandto such behavior how ishunger intensified by driven the by activation AgRP of neurons. Kageyama, Yuki M.D., This project willtest hypothesis the that accumulatingoxida tive stress in cells in the medial prefrontal cortex and nucleus accumbens and disrupts NAc) (mPFC effort valuation and adaptive reward-seeking behavior interfering by with the encoding reward-predictive of cues. This provide could important new insights concerning the prefrontal circuit-level mechanisms that mediate the spontaneous induction and remission anhedonic of behavioral states and their relation Daniel Ph.D., Joyce, is a reportedsion a variety symptom of mental of disorders includingseasonal and non-seasonal depression, bipolar dis and schizoaffectiveorder, He suggests disorder. may bethere a common brain pathway that is faulty in these disorders, which causes similar depressive symptoms in all them. of This explores candidatea project pathway discovered in animals, a forming”“non-image (NIF) pathway that links light captured theby eye that (but consciously is not perceived) with brain areas that size, pupil control circadian sleep, rhythms, alert ness, cognition, and, importantly, mood. Experiments will be conducted with LED-based light exposure in with people seasonal and nonseasonal bipolar disorder depression, and schizoaffective wellas disorder, healthyas The teampeople. will precisely light control activate to the NIF pathway to differentlevels of (“photoceuticals”)in hope finding the away alleviateto symptoms depression across disorders. multiple Erica Jung, Ph.D., - - - - - Icahn Medicine School of Columbia University, notes that notes Columbia University, University of Michigan, University of has identified Basic Research Basic Research Basic Research Basic Research

mechanisms that can relieve help symptoms in psychiatric disorders.proposed research The will study compensatory mechanisms impaired of decision-making. team The will modifyneurons in parietal cortexin rodentsso that they can be selectively inactivated systemic by administration understand theof drug the brain how clozapine. can To compensate lost functions, for they will inactivate a selected neurons while of group recording from other brain areas known exhibit to similar activity. decision-related They will test the hypothesis that other areas within the same circuit will change their activity compensate to the for disturbed incomputations the affected area. brain regions. This project seeks to address lackthe detailed a understanding the of neurobiological basis compensatory for the patterns instance for seen subjects. in control Therapy, in schizophrenia,patients may compensatehelp disrupted for neural activity down-regulating up- by or activity in various Danique Jeurissen, Ph.D., Danique neuralactivity patterns after treatment are the same not as ination the of genetic architecture these of diseases such as will be undertaken in this project. of theof molecular underpinnings and exam a comprehensive in mice understand to ANK3 how may contribute mutations of per development symptoms The to bipolar disorder. of a variant the of ANK3 thatgene causes a striking fore loss of brain inhibitory synapses.team The now examiningis the cellular, electrophysiological, and behavioral manifestations sonalizedcare patients for carrying unique that mutations disease to contribute necessitates a detailed understanding Paul Jenkins,Paul Ph.D., DNA, effectively switching particular on genes off. and This seeksproject discover to and understand the functional sig Magdalena Janecka, Ph.D., Janecka, Magdalena how corticalhow neurons encode core features defining theory of mind. nificance in “epimutations” of rare ASD—changes DNA in methylation that have severe effectson genes that influence autism risk. After discovering epimutations, the team will whetherexplore they are linked changes to in the genetic code; and investigate the characteristics the of genes with the epimutations, which will highlight the impact they may a developing baby. have on at Mount Sinai, Mount at is exploring the theory that risk ASDfor is partly influencedby changesDNA methylation, in an epi genetic process in which to bind molecules groups) (methyl 22 Young Investigator Grant Program 2019 tion. A subset of microRNA molecules localize to synapses to synapses localize molecules of microRNA tion. Asubset localiza miRNA called role its aprocess in to determine seeks memory.study and This for learning critical neurons between connections the of synapses, ment remodeling and the develop for important is protein The FMRP (FXS). Xsyndrome Fragile in crucial be may that processes in protein (FMRP) retardation Xmental role Fragile of the the define to systematically seeks Research, for Biomedical M.D., Kleaveland, Benjamin symptoms. to ASD related be may how they and regions these within cells neuronal in duplication of genes and deletion role the of the assess to more accurately culture in grown be can (iPSCs). pluripotent induced in cells cells stem These chromosome normal duplicated atypical, with replaced and eliminated be will chromosome that to formaring induced 16p11.2 the mosome containing be deletion/duplication will chro ASD.abnormal The with associations common genetic (deletions) (duplications) one or most of gain are the genes (CNVs) 16p11.2 agenomevariants in called region lose that number copy as such ASD. Aberrations cause can that errors to correct of chromosome therapy possibility the in interested Tae Ph.D., Kim, Hyun non-responders. of those from responders clozapine from neurons distinguish that features cellular-molecular hope of in biology delineating disease in implicated subtypes neuron cortical in specific clozapine of effect the examine will Dr. Kathuria cells, stem reprogrammed Using be. will responders clozapine who the advance in no to way know is there response, positive who aclearly for have patients taking worth often are risks these While myocarditis. and syndrome, metabolic of agranulocytosis, risk by increased complicated is use of Clozapine 6months. overine aspan clozap more antipsychotic to the treatments) do respond well or to respond to two (failure ment-resistant schizophrenia treat about with 50% of patients that says Hospital, General Ph.D., Kathuria, Annie to benefit. likely most patients to of interventions administration facilitate up and speed not recovery, only but also would optimize would acteristics char neurobiological and on neurocognitive based response treatment to predict learning machine Using psychiatry. in treatment for personalized developing patients—pivotal ual of individ characteristics neurocognitive and neurobiological to the according recovery to optimize interventions tailoring of capable engine amachine-learning to create hopes team The recent-onset psychosis. with sion for patients medicine” Tools/Early Intervention Diagnostic Tools/Early Intervention Diagnostic Basic Research Basic Case Western Reserve University, Western is Reserve Case Harvard University/Massachusetts Harvard

Ph.D., Ph.D., Whitehead Institute Institute Whitehead ------Vienna, Austria, will use deep brain stimulation (DBS) to stimulation brain deep use will Austria, Vienna, trying to understand more about difficulties people with more about difficulties to understand trying nisms determining how a we respond to aversive situations, determining nisms mecha neurobiological of the improve understanding our This study will draw upon data collected in the Biological the Biological in collected data upondraw will study This depression. people with in patterns activation circuit brain and symptoms and system immune the in dysfunctions between relation the Germany, studying of is Psychiatry, Christoph Kraus, M.D., Kraus, Christoph depression. immune of 250 patients) to amulti-layer depressed generate classifier and controls(50subjects 300 in markers of inflammatory range on awide by focusing function immune of the picture comprehensive a capture will The team patterns. imaging neuro and gene expression symptoms, ferent psychiatric by dif characterized are and depression exist in signatures immune specific that is over ing 450 The hypothesis subjects. study, (BeCOME) involv Disorders of Mental Classification Ph.D., Knauer-Arloth, Janine remodeling. or development synapse to regulate known are miRNAs some ofand these tions—due to impaired processing of visual stimuli within within stimuli of visual processing to impaired tions—due emo and faces, cues, social interpreting in have schizophrenia Kyrke-Smith, Ph.D, Madeleine time. of aversive real outcomes in avoidance guide signals how these and associations stimulus of formation cue-aversive projectionsmediates of cortical regulation how dopaminergic the to clarify is mice, in ducted con be this to project, of purpose The fashion. text-specific acon in aversive stimuli involved encoding in critically is (mPFC) cortex prefrontal input medial into the dopamine that suggesting results follow uponpast will der. The team disor bipolar depression and as well as disorders stress and anxiety including disorders affective problemcommon for all Kutlu, Ph.D., Munir it is experimental. which depression, in as well as forms, clinical option for severest established an is epilepsy, DBS treatment and which in nia, dysto possible to Parkinson’s if disease, results the extend and do not from dotreatment, and patients benefit DBS why some OCD hope to explain Dr. Kraus unknown. are changed are networks involved how in neuronal anisms OCD, mech the yet for refractory DBS in rates able success remark shown has OCD. research Recent with patients treat Diagnostic Tools/Early Intervention Diagnostic Therapies Next-Generation Basic Research Basic Basic Research Basic Vanderbilt University, hopes to hopes University, Vanderbilt

Ph.D., Ph.D., Max-Planck Institute University of Utah, is is of University Utah, Medical University of University Medical ------bbrfoundation.org 23

- - - - - Yale University, will investigate University, Yale genetic Boston University, notes that notes depressed Boston University, Columbia University, is studying Columbia University, the

Basic Research Basic Research Basic Research New Technologies

Diagnostic Intervention Tools/Early tory working memory task mice for thathas he developed. terns. Remarkably, inducing acute sleep deprivation (for example,asking by patients stay to awake all night)causes symptom relief and mood in improved approximately half patients patients. when eventuallyof But they sleep, rapidly relapse and their emotional state returns baseline. to This effectpotent of manipulating sleep suggests LewisDr. to arousal and emotional states in This depression. project seeks uncoverto neural mechanisms underlying these linked emo tional and arousal states, using new neuroimaging approaches (“fast neuroimaging”) that can measure neural dynamics associated with sleep throughout large-scale brain networks humans. in Psychiatric Genomics Consortium (PGC), and UK Biobank. Second, they will see what to extent rare genetic variants, polygenic riskscores from common variants, and available clinical risk factors identify may to be able individuals at greatest risk suicide in attempt for Yale- the independent cohort. Third,Penn they will investigate cell-type and tis sue-specific gene expression consequences of genetic common variationassociated with anxiety, and depression, suicide to identify biological novel targets treatments. for Laura Lewis, Ph.D., mood is accompanied energy low by and altered sleep pat that important biological mechanisms modulate jointly both Felix Leroy, Ph.D., Felix Leroy, neural circuitry in negative involved symptoms in schizo phrenia such as impaired social Dr. cognition andmemory. Leroy will examine the neural circuit mechanisms altered of socialcritical provide to cognition, hoping insights novel into neural circuit targets future for therapeutic interventions. willHe focus damage on the to CA2of subfield the hippo campusthat causes impairments in which plasticity, may be critically important producing the for social impairments observed in schizophrenia. molecular Thisunique area’s properties makes a promising it selective therapeutic target treatto abnormal social behaviors (including social memory and aggression) also associated with other neuropsychiatric illnesses. Ph.D., Levey, Daniel betweenoverlap anxiety, and suicide depression, in three phases. First, his team will common overlapping at look and rare genetic variation between anxiety and depression usingcohorts from the Million Program Veterans (MVP), ------Max-Planck Institute of Karolinska Institute, Sweden, Washington University School of Basic Research Basic Research Basic Research

Recent findings in mice implicate that intact SST interneu functioningron is importance in of the PFC working to Le will Merre Dr. obtainmemory. data through an audi will investigate a connection between cortical interneurons that express a peptide called somatostatin (SST), specific oscillatory patterns, and impaired the working memory, latter being a cognitiveobserved deficit in schizophrenia. ing reduce to risks executive of dysfunction and subsequent psychopathology in childhood. Le Ph.D., Merre, Pierre pathology model for possible in schizophrenia. project The neuroimaging, parent-child observations, and developmental assessments, inform to hoping early parent-child interventions that enhance infant brain connectivity during a sensitive period brain of plasticity targeting by dysfunctional parent flexibility—buildingblocks emergence of later for executive function, which is impaired in many brain disorders includ Lean ingDr. ADHD. focuses dysfunctional on parenting in early interactions, mother-infant a strong predictor of impaired executive function and brain She development. will access an infant population undergoing multimodal opment of self-regulation, of executive andopment attention, cognitive RachelLean, Ph.D., ponents, and eachponents, how behavior. to contributes basis vertebrate of social behavior have implicated the “social a set evolutionarily of behavior network,” conserved brain areas. This project seeks determineto its exact circuit com model because they display spontaneous social behavior with robust individual variability. is characterize to possible It behavior in hundreds animals of and record whole-brain to neural activity cellular at Studies resolution. the of neural Medicine, wantsknow during to when, child development, brain networks are disrupted, altering the very early devel Neurobiology, Germany, is studying Germany, theNeurobiology, neural basis social of affiliation, a behavior that isimpaired with in people ASD and schizophrenia. will He use zebrafish, idealan vertebrate JohannesLarsch, Ph.D., patients. will She study the structure and function visually of responsive neurons and their synapsesin animals in which the Arc has gene been knocked comparing out, results with their wild-type littermates, which serve as controls. the visual cortexthe of brain. This project is concerned with synaptichow pruning is regulated may go awry and it how in schizophrenia. At the focus is called a gene Arc that reg ulates synaptic pruning and whose activity is decreased in is studying impairment auditory of working memory as a 24 Young Investigator Grant Program 2019 sizes that the relationship between cortical glutamate levels levels glutamate cortical between relationship the that sizes Amanda Lyall, Ph.D., Amanda 15 over last the years. diagnoses ADHD in increases disproportionate and duration, sleep prenatal reported shorter complications, burden of pregnancy a disproportionate is there which in populations, Latin within relevant particularly is subject The inflammation. prenatal by maternal mediated neurodevelopmentis sleep on offspring maternal of influence the whether and control abilities; on inhibitory toddlers’ (~12at toddlerhood sleep months); maternal of influence the (~4 again and weeks) at infancy fMRI by resting measured as offspring in cortex) (ventral striatum-orbitofrontal circuits Ph.D., Lugo-Candelas, Claudia expression. and storage memory fear sex-specific in (LS) septum lateral the called region role the of abrain by examining gent vulnerability diver this underlying mechanisms circuit-based and cellular- the models animal in investigate will project This disease. psychiatric for fear-based strategies treatment and anisms to pinpoint hopes mech Dr. sex-specific Lucas males, than memories differently fear express and encode how females ing women By more are understand susceptible? Why illnesses. these women in with of life to poorer quality leads severity symptom greater that and conditions, psychiatric fear-based Elizabeth Ph.D., Lucas, outcomes. clinical on important individuals differentiate meaningfully patterns data device smart within clusters if determine outcomes and clinical and 9-month data longitudinal between relationship the to understand learning apply machine will over The team 9months. individuals 40 in functioning cognitive and on variability mood data as well as of disorder bipolar markers biobehavioral to track devices smart use will Her team trajectories. homogeneous disease with patients classifying for methods insufficient with along patient from to patient, course and characteristics illness in variation to wide owing diminished are disorder bipolar Women’s with patients outcomes in that Hospital, proposes Ph.D., Lipschitz, Jessica measured prenatal maternal sleep duration on frontostriatal on duration frontostriatal sleep maternal prenatal measured of influence theobjectively Theinvolves project measuring of ADHD. developing child to the risk with connection its especially on offspring, impact its and pregnancy during deprivation sleep maternal between relation the studies /NYSPI, Hygiene, Foundation for Inc. Mental Research notes that women are twice as likely as men to experience men to experience as likely as twice women are notes that Tools/Early Intervention Diagnostic

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- - - - provide a temporal map of the proteins that are expressed in in expressed are that proteins of the map provide atemporal and parent dyads. parent and in symptoms adolescent and depressive 100 inflammation, of protein markers and molecular relationships, of social assessments repeated through explored be will This toms. promote symp depressive turn in blood, which peripheral in cytokines called molecules pro-inflammatory circulating of levels higher and genes anti-viral and pro-inflammatory expression of the in reflected cascades to inflammatory lead friends) relationships or (e.g.,parents with social specific of multiple types across features maladaptive that proposes Dr.Manczak Specifically, risk. to confer embedded ically biolog become can experiences environmental how salient for explanation an offers that parents their and adolescents in of symptoms model depressive a social-immunological early-onset and psychiatric disorders such as autism spec autism as such disorders psychiatric and early-onset in impaired is ability This responses. appropriate behavioral to generate processes mental between to switch ability our of understanding inform help will flexibility of behavioral signatures Themolecular identified behaviors. flexible with associated are that ensembles neural ofgroups called neurons Ph.D., Mabb, Angela disorder. bipolar 10 early-course in with patients of glutamate assessment the to specific MR-PET) (GluCEST and data imaging advanced of types two collect is to The plan Psychosis. Project for Early Connectome Human by the recruited been who already have disorder bipolar with patients of well-characterized ulation pop thelarge access will The team receptors. tropic glutamate on metabo focusing interventions therapeutic more effective development the in of to assist evidence provide foundational to seeks project disorder. bipolar This with patients in rant aber is brain of the mGluR5 expression in receptors the and Dr. Mani will use two types of imaging to study 20 people 20 to study of imaging types two use will Dr. Mani patients. treatment-resistant the 50% of other in benefits these whyknown does alsonot it provide not is it effects, eficial ben its of Yet 50%. exerts how TMS it not since is clear yet symptoms in areduction with or TMS stimulation magnetic transcranial called method stimulation non-invasivethe brain respond favorably patients to of antidepressant-resistant half Ph.D., Mani, Merry Ph.D., Erika Manczak, flexibility. cognitive diminished with associated conditions health mental to treat targets molecular of identification to the lead may anorexia depression, and disorder, stress post-traumatic disorder, schizophrenia, trum

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Downstate, is interested inEEG coherence—the degree of synchrony inbrain oscillatory activity between neural net orders suchorders as schizophrenia.team The will drawupon the vidual differences neuralin connectivity among unaffected male and female adolescents and young adults throughout a key period risk of the for onset psychotic of illness (ages nicotine, and(alcohol, cannabis disorder). use and DSM-5 theyImportantly, will examine thesehow associations differ among males and females and age. by Ph.D., Michelini, Giorgia identifyEEG signatures risk in of depression adolescence. for Several atypical EEG patterns canbe observed in people the D1 and dopamine D2 receptor-expressingthe D1 subtypes. These exhibit dramatic differences in activity and effects on drug reward. This project aimsidentifyto precise the epigenetic mechanisms that establish and preserve the molecular pathol ogyin these distinct striatal subpopulations. Ph.D., Meyers, Jacquelyn works in two brain regions. Coherence has been particularly useful in the study normal of brain and dis development Collaborative the Study on Genetics Alcoholism, of with lon total assessments)gitudinal in addition to EEG data (14,495 offspring32 from to 12 data,aged GWAS available 3,911 on families densely affected with UseDisorders wellAlcohol as as community comparison families.team The will examine whether genetic risk schizophrenia for is reflected in indi and this how is influencedby substance 12-32), use behavior the locus coeruleus. Thisproject seeks to understand how two criticalbrain structures, the ventral tegmental area and the locus coeruleus, communicate during stress. In particular, McCallDr. hypothesizes that the brain circuit between these two structures is enhanced in during chronic stress, perhaps contributing the to negative behavioral consequences stress. of This will be investigated in animal studies. Philipp Mews, Ph.D., Sinai, is exploring the hypothesis that permanent changes inchromatin structure—the bundle complex in which our is DNA packaged in the cell—underlie the dysregulation of activationgene patterns characterizing drug addiction. There is currently direct no link between drug-induced alterations in chromatin and the aberrant regulation gene observed during Mewsrelapse. seeks Dr. determine to which neuronal sub types are within responsible the accumbens, nucleus which is composed two of opposing types medium of neurons, spiny revealed disruption major genes of and proteins associated with excitatory neurotransmission in a brain area known as - - - - Gladstone Institutes/ Gladstone Ph.D.,

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Next-Generation Therapies that studies prior the on brains suicide victims of have Jordan McCall, Ph.D., ciated with ASD and intellectual disability a protein form incomplex the developing brain.This suggests they may regulate neurons the and of production glia during the gen theeration of cerebral cortex. In this proposes he to project determine whether and these how genes cooperate regu to late brain Specifically development. hopeshe to shed light whether complexeson that and protein how participate in chromatin remodeling regulate neurons the of production and glia during the of cerebral the development cortex. Pierre Mattar, Ph.D., Canada, has discovered that two genes asso prominently testthe hypothesis that ADHD genetic risks are strongly more associated with and depression anxiety in females than in males; and whether and depression anxiety genetic risks are stronglymore associated with ADHD in males. is to comprehensively characterizeis comprehensively to the sex-specific impactsof genetic risk variants clinical on diagnoses ADHD, depres of and anxiety,sion, in children and adults. will She use data case-controlfrom patient samples diagnosed of individuals, as well as a sample 75,000 children of assessed in mental health clinics a variety for psychiatric of will She problems. female bias in and depression anxiety. The aimof thisproject JoannaMartin, Ph.D., are striking sex differences in prevalence the of ADHD, anddepression, anxiety, with a male bias in ADHD and a social cognition and attachment behaviors in humans. This seeksproject determine to the changes in neural activity and expressiongene that underlie deficits attachmentin voles in that carry in mutations genes that have been implicated in neuropsychiatric disorders. Pioneering work in thePioneering work prairie has vole identified vasopressin and oxytocin as critical mediators pair of bonding, as well as Devanand Manoli, M.D., Manoli, Devanand withare who depression initiatingmajor clinicala course of The high-frequencyaimidentify to is rTMS. imaging-based biomarkers that can inform target engagement theat onset treatment.of University of California,University of San Francisco, is working with prairie voles—small rodents that display strong social attachment behaviors betweenpeers and develop enduring pair bonds between mates—to study social behaviors and their disruption in anxiety- and depressive-like behaviors. 26 Young Investigator Grant Program 2019 Canada, seeks to validate in a pilot test a new, cost-effective anew, a pilot in test cost-effective to validate seeks Canada, cytes and neurons. The research, using reprogrammed stem stem reprogrammed using The research, neurons. and cytes oligodendro in occurs how protein biosynthesis determine to matter. Dr. white of the Moon seeks function and mation for for the important particularly appears which synthesis, for protein pathway bio molecular on the She focusing is understood. not well are function to formand matter white allow that processes molecular and cellular the notes that Stephanie Moon, Ph.D., of treatments. course extension once-daily followed by 25-day aconventional phase 5-day 6-times-daily protocol the initial employssessions, an enable home multiple would Since daily use ministration. to simple enable self-ad enough techniques using tiveness, tolerability, safety, cost-effec fault-tolerance, and maximal a novel rTMS test for will protocol optimized setting, ical aclin in conducted to be depression patients, unipolar 60 in study I Dr.Phase says This Miron. to medication, compared costs operational and acquisition high and by complexity its impeded been adoptionfor has depression. Its widespread rTMS called stimulation non-invasive brain ofway delivering M.D., Miron, Jean-Philippe networks. brain aberrant of retraining goal the with stimulation, selective to trigger biomarkers for DBS using approaches is to develop neurosurgical do not.goal others The why and some respond to DBS patients therapy help explain may of. This it part is network brain the and region striatal the ventral of neurophysiology fine-structural the characterize is to foraim OCD. DBS treatment The undergoing who are patients in striatum ventral the from data electrophysiology record will Dr. ago. Miller years 20 nearly inception its since OCD (DBS) to treat stimulation for brain deep a target been has (NAc) nucleus accumbens the VS, the converge. Within areas many from inputs where motivational brain the in deep a region is (VS) striatum ventral the notes that Minnesota, Miller,Kai M.D., study. ADEPT the using followed up adulthood, into young 550 girls teenage of sample acommunity from data conducted onbe available will This project disorders. of depressive onsets first predict to help improve ability they our whether examine and tools, analytic cutting-edge using for disorders depressive of risk EEG signatures to identify seeks research This symptoms. showing peoplebefore start onsets first future predict can development the predate of depression and alterations these do not whether know but we still disorders, depressive with Next-Generation Therapies Next-Generation Therapies Next-Generation Tools/Early Intervention Diagnostic Ph.D., Mayo Clinic College of Medicine, of Medicine, College Clinic Mayo University of Colorado, University Boulder, University of University Toronto, ------protein biosynthesis, it may be possible to see how defects in in it how possible to be see may defects protein biosynthesis, involved in genes in iPSCs the mutations in introducing matter. By white of the of cells function and formation the to support compartmentalized is how protein biosynthesis and of whether examination direct (iPSCs), allow cells will with major disorder. depressive with patients in feasible is training biofeedback such hope that is The real-time. in activity VTA own their watching while patterns thought certain to use trained are they if unteers vol healthy in changed be can VTA of the activity the that haveshown studies session. Previous scanning MRI field ultra-high an during activity VTA own their to modulate majordisorder depressive with individuals to train trial trolled con randomized of a consist will project depression. This in problem the of with motivation linked area abrain (VTA), area tegmental ventral of the muchprovides improved images that procedure MRI field ultra-high an developed has Sinai, Ph.D., Morris, Laurel neurons. and of formation oligodendrocytes and function the with interfere pathway protein biosynthesis the an animal model of depression, the team will investigate the the investigate will of model depression, team the animal an Using transmission. neural impacts this whether and cytes astro on stress chronic of effects of the evidence little is there yet bout of stress, by acute asingle impaired is function cyte astro that suggests data Preliminary function. brain normal Ph.D., Ciaran Murphy-Royal, decision-making task. areward-based to perform directed non-humanprimates in tested be It regions. will brain targeted precisely in barrier blood-brain to open the used be can ultrasound focused lipid microbubbles, with Combined region. targeted the in or neurons inhibit stimulate directly and structures brain deep to reach skull the through beam ultrasound an sends (FUS), which ultrasound focused non-invasively via cuits cir neural to receptor.modulate project attempts the This express that genes the to deliver methods invasive require also Unfortunately, DREADDS regions. brain targeted in pharmacologically activity neural to modulate drugs) designer by activated (designer exclusively receptors DREADDS use to involves is surgery, which stimulation, brain deep with to treatment alternative apromising disorders, for certain that Ph.D., Silva, Munoz Fabian These cells play key roles in maintaining many aspects of aspects many maintaining in roles key play cells These arodent of in model depression. astrocytes, cells, brain nal of non-neuro role the of afamily investigate will Canada,

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of ASDof and associated inflexible behaviors that characterize restrictivethe disorder and (e.g., repetitive behaviors). Agnes Norbury, Ph.D., Sinai, wants test to new theories suggesting that only people usenew information update to an fear older memory if they think that the same causes are events for during responsible project is performproject analysis to joint traits, multiple of allowing identificationfor of both sharedof and unique components genetic risk, and with increase great potential statistical 1) to the for identificationpower of risk loci2) furtherand eluci date the etiologies genomic the of tested traits. Existing large rare-variant datasets from autism and schizophrenia cohorts theprovide basis this for research. Ph.D., Nomi, Jason individuals has shown that increased brain signal variability is prevalent inmore younger individuals and those perform who bettertasks on flexible of cognition. This makes brain signal variabilitypromisinga new measure and flexi development of cognitionble that can be used investigate to the neurobiology The research The mechanistic provide could insight diseaseinto causation the at molecularlevel, bridging rare of the role and common genetic variants associated with various disorders. Ph.D., Neuhofer, Daniela Hoang Nguyen,Tan Ph.D., Carolina, studies cannabis character use disorder (CUD), ized tolerance, by difficulties tocontrol use, craving, and withdrawal symptoms after discontinued use. seeks She to characterize and understand neuroadaptations in reward circuitry that might CUD, as to contribute wellas anxiety and depressed mood associated with cannabiswithdrawal. In rodents, hopes reveal she to a circuit-based mechanism underlying cannabis craving and withdrawal-related emo tional symptoms CUD of that a biolog could open to help ical strategy future for possibilities in drug for development treating cannabis addiction. a new characterization for approach ASD of neurobiology inspired computational by neuroscience that relies mea on sures brain of signal variability. Previous research in typical University, has developed a multi-traitUniversity, method (multi-trait AndTransmission Association De to novo test, mTADA) perform pairwise analyses six of neuropsychiatricdisorders using family data, and single-trait methods that integrate rarevariant, gene-expression, and pathway information for deeper analysis each of disorder in isolation. The aim in this - - - - - The Broad The Institute of MIT and Harvard Medical seeks School, to The Rockefeller University, The RockefelleraimsUniversity, to Basic Research Diagnostic Intervention Tools/Early Diagnostic Intervention Tools/Early

ment of a metabolica of subtype ment depressive disorder major by of validating brain biomarker of a novel Specifically, plasticity. provide a precision medicine a precision diagnosis modelprovide of and treat derived from human stem cells induced pluripotent (hiPSCs). genome organizationgenome in neuronal cells, modulating expression psychiatric of test the hypothesis, risk Nehme genes. Dr. To will deletion neurons investigatein the effectsof 22q11.2 Ralda Nehme, Ph.D., acceptability the of digital training, and feedback elicit to from community health improving for workers the course design and content. attitudes severe about mental disorders. They will also employ qualitative focus discussions group ascertain to feasibility and develop and pilot-test the feasibility, acceptability, anddevelop and pilot-test initial impactdigitala of training intervention for community health workers, called ASHAs (Accredited Social Health Activist), in the detection and referral severe of mental dis John Naslund, Ph.D., team The orders. willmeasure initialprogram impact using assessments pre/post knowledge of and skills and general anisms insulin of action in relation acetyl-L-carnitine to (LAC) in patients 50 with as depression major compared non-diabetic 50 of a group to age subjects and sex-matched psychiatricwithout disorders. Greater understanding the of reciprocallink between LAC andinsulin action in major depressivedisorder could be instrumental in uncovering targetsnovel regulate to brain plasticity and ultimately lead personalizedto medicine strategies. the will project identify to help central and peripheral mech Carla Nasca, Ph.D., and depression-like behaviors in mice. cumulative effectsof stress on astrocyte structure, function, and impact neural on transmissionand They plasticity. also planspecifically to target astrocytes, seeking to alleviate stress opment of clinical of opment skills among community health workers early for detection and referral severeof mental disorders in primary care settings in rural India.objective The to is leverage digital technology support training to and devel mosome 22 ismosome associated with increased risk psychiatric of disorders, and is the highest known genetic risk factor for schizophrenia. its high Despite prevalence, little is known theabout molecular mechanisms that lead psychiatric to symptoms ina subset those of carry who Thisthe mutation. willproject deletion alters test the hypothesis that 22q11.2 Harvard is studying University, a vulnerable location in the a deletion in where chrohuman called genome 22q11.2, 28 Young Investigator Grant Program 2019 neural circuit mechanisms of mesoprefrontal VTA dopa VTA of mesoprefrontal mechanisms circuit neural the examine will deficits, social autism-like studying who is pathology using GPS traces drawn from mobile from phones or drawn GPS traces using pathology or psycho other of anhedonia presence the for detecting approaches health development to the lead it could of digital Oliver,Jason Ph.D., ASD. to manage strategies treatment avenues for and future novel targets tify is to iden aim larger The chemogenetics. and gene delivery viral-mediated using stress by early-life induced behaviors asocial in VTA neurons roles dopamine projection-specific of to define and stress; life early- PFC the in neurons following of layer 2/3 pyramidal changes functional and structural to determine VTAneurons; dopamine PFC-projecting affects stress early-life to exposure how are to define goals The stress. by elicited early-life behavior asocial underlying circuitry one neurons, major of componentsmine the of stress/reward Ph.D., Won Oh, Chan possible. currently is depression than women for postpartum at risk identify helps to screen better molecular this if to determine factors risk social and psychological known existing with sensitivity of hormonal combine measures biological will The team hormone-sensitive in gene expression. change of dynamic modelling by computational described as sensitivity monal hor maternal assess directly will that system collection a novelusing blood a to develop simple test, blood findings such on to build aims project depression. This postpartum for risk increased and sensitivity hormonal maternal cating impli evidence notes growing Canada, Institute, University Kieran Ph.D., O’Donnell, events. about negative learn how they to test game online an or PTSD, disorder using anxiety an with individuals in behavior avoidance excessive explain can theory new this if test will The team factors. underlying same of the result the are they that unlikely is that means events these across context in difference the that reasons individual the if harmful being object or situation older of that memory an to update fail may safe object or is situation an that learning new words, other In episode. learning current and memory fear original the both home, limited number of fixed activity points). Long-term,activity of number fixed home, limited (e.g. spent outside of time the anhedonia lack or perpetuate cause that intofactors insight mayimportant provide This anhedonia. with associated signatures pattern activity the to identify GPS technology use Dr. Oliver will patterns. activity human activities—affects pleasurable in engaging or pleasure pursuing in of loss interest anhedonia—the way Tools/Early Intervention Diagnostic Basic Research Basic Basic Research Basic Duke University, the in Duke interested is University of University Colorado, Denver, Douglas Mental Health Health Mental Douglas - - - - - participants simply increase their time spent outside time home? their simply increase participants (e.g. goals intervention should inform might that mation infor patterns, activity on psychotherapy of effects of the possible determination make It also could devices. wearable GABAergic circuitry and identify potential new targets for targets new potential identify and circuitry GABAergic inhibitory role the of midbrain to understand seeks a subclass of glial “helper” cells that are often overlooked in often are that cells “helper” of glial a subclass are Astrocytes process. this in rolethe playedby astrocytes in interested particularly become has and schizophrenia, as such disorders brain in of cognition underpinnings cellular and molecular the understand to better aims of Medicine, the postnatal period. the postnatal and pregnancy during for depression treatment leads new of developing aim ventions the (metabolite alterations) with explore possibleinter also will It offspring. developing in factors risk on insights deliver could the research offspring, outcome of behavioral the and microbiome,the metabolites, By assessing cells. human in and rats in barrier blood-brain the cross to metabolites elucidate how is altered goal second A offspring. mother to the the from ment transmitted are treat antidepressant microbiome gut the duein to maternal alterations how investigate to body. the seeks in project This maintenance serotonin with microbiome the interacts that evidence 95% clear is there body’s of the that and serotonin contains gut human the notes that Netherlands, Groningen, Jocelien Olivier, Ph.D., locations?) different many in of time amounts Spend novel small in locations? Spend time deficits, including their role in the pro-cognitive effect of effect the their rolepro-cognitive in including deficits, cognitive and cognition in by astrocytes receptor expressed alpha-7 the rolethe of study nicotinic will The team research. Papouin, Ph.D., Thomas for loss. its or compensate KCC2 function boost that drugs of several potential therapeutic tivity. the Dr. to test hopes Ostroumov sensi reward blunted behavioral with associated commonly is which signaling, dopamine attenuates turn ity.in This excitabil circuit GABAergic midbrain to increased leading receptor-mediated inhibition GABAA impairs dysfunction KCC2 neurons. GABA VTA in of located KCC2, function decreased via circuitry inhibitory midbrain dysregulates stress that indicates rats in data Preliminary at synapses. inhibition KCC2 involved regulating is in behaviors. depression-like influence KCC2 will of aprotein called manipulation ular or molec pharmacological if to determine seeking anhedonia, of model arat use major disorder. depressive He will treating Alexey Ostroumov, Ph.D.,

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Diagnostic Intervention Tools/Early Diagnostic Intervention Tools/Early Medicine, observes that drug addiction isassociated with levels dopamine low of release in the striatum, the brain’s reward features Many prominent center. addiction of stem dopaminefrom low release, including reduced salience of non-drug rewards. Studying the origin dopamine low of function in chronic drug users the key may hold finding to newstrategies treatment will for He and prevention. use a imagingnovel technique called NM-MRI measure to the accumulation neuromelanin of dark deposit) pigmented (a in the substantia nigra in eighty with a history 18-year-olds drugof use. Neuromelanin is a byproduct dopamine when is made. aim One is establish to a definitive link between NM-MRI level and cumulative adolescent drug use. type–genotype association toward greater understanding of underlyingcausal processes between and depression major psychologicaland medical conditions, environmental risk, and brain region and cell types. Brian Rash, Ph.D., gyrus—the ridges that characterize the outward appearance theof cerebral cortex. Abnormalities gyral of size and pattern have been reported in neuropsychiatric diseases ranging from autism spectrum and bipolar disorders schizophrenia. to He approaches incorporating data multiple types: environmental, clinical, neuroimaging, and genomic. This project seeks to sum leveragetotal the traitsof “phenome”—the expresses by a cell—and sequencing identify to genome genetic variants conferring risk, depression specific subtypes and symptoms, andcorrelated traits. pheno ideabeyond The move to is Mu Qiao, Ph.D., underlyingcomputation the balance the of two, and deter to mine this how process is altered in mouse models ASD of and schizophrenia. Greg Perlman, Ph.D., Peterson, Ph.D., Roseann University, begins withUniversity, the premise that deeper a under standing causal of processes in will depression require novel anisms decision-making of and decision-making deficits in psychiatric disorders. project The aimsto understand how a mouse weighs current sensory and prediction input from previous experience decision-making, for identify to neural apply computationalapply models decision-making of and its underlying neuronal dynamics understand to neural mech behavior, akinbehavior, human to clinical findings. ------Columbia University, is inter Columbia University, Princeton University, notes that notes Princeton University, University of Pittsburgh, University of is addressing

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a “two-hit” mouse early-life model of and adult stress in male and female mice, wherein mice exposed early-life to stress inpostnatal-a sensitive window have increased sensitivity stress to in adulthood andhigher rates depression-like of poorer antidepressantpoorer has treatment She outcomes. validated CatherinePena, Ph.D., opment of synapses of opment in striatalneurons. This help couldwork determine different how genetic environmentaland insults affectsignalingDA early normal and brain development. striatal release DA in response stimuli to and determine it how modulates a signaling mechanism that is critical the for devel new experimental paradigm striatal monitor to levels and DA signalingDA-induced in freely behaving developing mice. This will maketo it characterizepossible earlydynamics of Rui Ph.D., Peixoto, psychiatric disorders. ulation of versions of a protein kinaseulation a protein of versions of called GSK3. These experiments sex-specific combine circuitlevel investigation with neurodevelopmental rescue determine to the efficiency pro-cognitive novel of therapeutic interventions neuro for frontal cortex, Passecker including Dr. working memory, seeks test to sex-specificrescue workingof memory deficits and neurophysiology in his selective model by rodent manip characterized age pronounced by disturbances and sex-related in cognitive tasks that the on hippocampus depend and pre estedin identifying sex differences neurodevelopment in that bear cognitive upon deficits neuropsychiatricin dis Johannes Passecker, Ph.D., Passecker, Johannes the is receptor expressed all by cell typesin the central nervous system, has been its role systematically not studied. cholinergic therapeutics. Enhancement this of has receptor ameliorate to approach becomemajor a cognitive deficits asso ciated with schizophrenia and Alzheimer’s disease. Though orders likeorders schizophrenia. with mouse a Working model human microdeletion syndrome, which is the of 22q11.2 the question of how dopaminethe signaling how question of (DA) is regulated during influences early and it how development the mat uration circuits of in the striatum. will Peixoto take Dr. advantage two of new technological advances establish to a cally studied. will She use bioinformatic a combination of analyses and pharmacological testing in a mouse modelto better understand early-life why stress is associated with early-life stress alters brain yet the resulting development, molecular changes in the brain that may mediate altered response antidepressant to drugs been systemati have not 30 Young Investigator Grant Program 2019 greater understanding of these sensorimotor processes, both both processes, sensorimotor of these understanding greater A ASD, appear. long symptoms other with before old infants 6-month- visible in are object manipulation in Impairments order of representation in object identity.to form a holistic signals tactile motor with exploratory actions integrate must The brain sensation. motion tactile and exploratory dinated touch-coor by active objects identify can animals other and Humans object recognition. during of layers cortex the across flowinformation the of to reveal methods acombination use Ph.D., Rodgers, Christopher mu its receptor properties. through acts phine buprenor that not work, does itnaltrexone suggest would Conversely, properties. if common kappa-antagonism via are mediated effects anti-suicidal their that suggest would of buprenorphine, this to that equivalent is of naltrexone efficacy the for If opioid-use used treatment. disorder also is and receptors kappa mu and both blocks which naltrexone, with compared ideation suicidal on effect its examine will the team effects anti-suicidal of the mechanism the tigate To ideation. suicidal of depression and treatment inves the in for promise opioid-use shown treatment recently disorder, has by opioid-use Buprenorphine, a patients. experienced disorder states emotional negative the underlying be may receptors, opioid of brain opioid of kappa a class receptors, activation show that studies human and animal behavior. Several forsuicidal risk opioid-use at significant patients disorder M.D., Rizk, Mina functioning. behavioral underlie that systems neuronal and of pathways function altered to may lead turn in which offspring’s the in brain, gene expression and DNA methylation in alterations stable to genome-wide, depression leads prenatal that is hypothesis progeny. the in The functions working behavioral and brain altered and depression (and/or exposure) natal antidepressant pre between link the mediate that correlates biological the assess She to hopes offspring. in disorders rodevelopmental of risk theneu on influence greater has to antidepressants depression or exposure maternal underlying whether mine to model deter a mouse use will Switzerland, of Zurich, Ph.D., Richetto, Juliet brain. developing the in generated are features of how these theories current two to assess he aims monkeys, macaque with research In ities. abil cognitive higher hence enable our and cortex cerebral of the area surface the convolutions, increase which cortical of formation the behind mechanisms the to understand seeks

Basic Research Basic Basic Research Basic Research Basic Columbia University, will study, in detail, study, University, Columbia detail, in will Brain Research Institute, University University Institute, Research Brain Columbia University, Columbia will ------mize clozapine administration. clozapine mize thebody. is toin aim opti The breakdown clozapine affect may that variations to discover DNA sequenced their have who will of clozapine “poor 40 metabolizers” of identifying hope the with on inpatients clozapine, some Chinese 1,000 involve of recruitment will research This medicines. other not helped by who are to patients places, many in use, its have restricted which side effects dangerous has clozapine symptoms, psychotic controlling in effective very Although clozapine. medicine antipsychotic of the to breakdown poor predisposition for of agenetic patients apopulation study Hospital, People’s Beijing will Anding Republic of China, Can Ruan, Ph.D., Ruan, Can stress. of inescapable consequences related fear- and social for the raphe necessary neuron serotonin is dorsal distinct of genetically 2) type and which stress capable by ines raphe activated neuron serotonin is dorsal distinct of genetically 1)Dr. type to identify proposes Root which neurons). (glutamate-serotonin glutamate neurotransmitter excitatory the with serotonin co-release others while neurons) Some solely cell-types. tinct serotonin release (serotonin-only dis genetically into two divided raphe are serotonin neurons Ph.D., David Root, therapeutics. eventually and interventions to earlier lead ASD, in could and health in engrams by the induction of new plasticity. of induction new by the engrams these to access normal find of reinstating ways to efforts advance could and adults, memories in of infant tionality func and thepersistence light on shedmay This retrieval. on memory manipulation of engram-cell effect the study He stored. will memories are it that proposed is which within units biochemical are Engrams amnesia. of infantile models rodent various with technology engram-labelling developed recently development stored in memories are by integrating probe how He loss. will memory and ofbiology amnesia the from Toward to learn end, he wants this circumstances. traumatic in access memory targeted modify that treatments ablethenbe may we to design memories, to specific access how brain’s to control the we understood if normal that gests Tomas Ph.D., Ryan, and fear-related consequences of inescapable stress. Dorsal Dorsal stress. of inescapable consequences fear-related and responsible social for rapheis neurons serotonin the dorsal of activation the that establishing to contribute to research

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ing alcohol-seeking behaviors. focus The will be molec the ular determinants alcohol-evoked of changes plasticity on specificat to nucleus inputs of bedthe striathe terminalis (BNST), a region deep in the brain which integrates wide from acrossspread input the brain and sends to projections downstreammultiple areas that behavior control and emo Santa Barbara, will the probe underlying circuitry support Samantha Scudder, Ph.D., Scudder, Samantha tional states. As this region is also known be to a key regulator stressof responses and anxiety-related knowledge behavior, theof baseline wiring and inputs the of of BNST outputs will additionally inform understanding this how of region reduces or anxiouspromotes states. AndreyShabalin, Ph.D., norphin. Thisproject explores hypothesis the Pdyn+ LC that neuronsare important mediators stress of response, and that dysfunction within this neural circuit may be an underlying chronic to stresscontributor disorders. Ph.D., Schwerdt, Helen aims characterize—at to Technology, levels neu multiple of rochemical and neural electrical activity across basal ganglia and cortical sites—the neural sources key of behavioral vari ables that are compromised in mood disorders. makes She a critical firstto examinestep: corticostriatal pathways and striatal dopamine signals given the simultaneously, strong connection these of fundamental brain processes in mood disorders. will She usetools that extracellular rapid probe dopamine fluctuations concurrently neuralwith electrical activity fromwide a distribution in sites the of striatum of behaving nonhuman primates. hope is The that these types multi-modalof measurements will development to contribute diagnostics improved of and treatments. ing methylation—a how epigenetic form of modificationof expression—maygene impact suicide risk. Since increased risk suicide deathfor hasbeen welldocumented inschizo and and PTSD, hasphrenia, depression, bipolar disorder, strong links environmentalto exposures, argues she that suicide death is a prime phenotype a methylation for study. Thismethylome-wide project pilot well-powered a is associ studyation population-ascertained of suicide death, testing differentialfor methylation in bothbulk blood tissue and within diverse blood-cell types. Results will be compared with thosein schizophrenia andMethylation depression. markers biological to may point mechanisms and processes otherwise undetectable.

- - - - St. Jude Children’s Research Children’s Jude St. Salk Institute Biological for Universidade Federal de Sao Paulo, University of California, University of Irvine, is Basic Research Basic Research

Diagnostic Intervention Tools/Early Studies,that pointsout sensors environmental of stress are wellnot understood, although detection such of stress likely investigating molecular implications in the circadian clock and depression of antidepressant treatment. The circadian co-express NE peptide precursor and the prody gene opioid Schwarz recently identified a neuronsof populationLC that Lindsay Schwarz, Ph.D., Schwarz, Lindsay from prefrontal cortex mice of with depression-like behaviors generated chronic by social-defeat stress. that orients us to the 24-hour cycle. Dr. Sato’s lab regards thatus orients thethe to Sato’s 24-hour cycle. Dr. circadian clock as a key in the operator onset depression of and the action antidepressant of treatments such as rapidly acting further ketamine. low-dose this To they work, will profile activitythe of circadian genes acrossat genome the different using timescellsof day, harvested postmortem clock is the biochemical time-keeping mechanism in our cells Shogo Sato, Ph.D., tal challenges and neurological to contribute disorders by regions new while into jumping genome neurons are being born. Depending the on insertion they site, may alter gene expression, and lead changes to in neuronal function. This research will explore that possibility. involves a complex interaction a complex involves genetic of and environmental factors that alter neural function. Sarkar Dr. is interestedin segments that DNA of around jump in the called genome, Sarker if aberrant wonders Dr. elements. LINE-1 L1 L1 or activitycould be maladaptivea response environmen to Anindita Ph.D., Sarkar, microRNA expression from serum exosomes adolescents of before and after the transition psychiatric to disorders. potential biomarkers transition of psychiatric to disorders and currentlyimprove available prediction, evaluating tools by for enables them cross to the blood-brain and barrier, thus, some studiesexosome have targeted neuropsychiatric disorders to identify potential hopes identify Santoro to biomarkers. Dr. the cell its origin, of with its specificmembrane markers and intracellular including content, microRNAs. Their sizetiny MarcosSantoro, Ph.D., Brazil,is intrigued exosomes—small by con bubble-like tainers floating outside cells that found are in fluidsbody serum, likesaliva, CSF, and urine. represents The exosome ing, anxiety, which depression, is thought and promote to posttraumatic stress This disorder. implicatesbrain a area calledthe locus coeruleus a crucial (LC), arousal in center the brain and an important source Dr. norepinephrine. of Hospital, isHospital, interested in aberrant signal norepinephrine 32 Young Investigator Grant Program 2019 risk for schizophrenia in the absence of common polygenic of polygenic common absence the in for schizophrenia risk conferring in aresufficient they or whether not effects, large individually have alleles some identified While (SCHEMA). Meta-Analysis Exome-Sequencing e.g., Schizophrenia the variants, coding ultra-rare using genes risk individual cated haveimpli that for schizophrenia studies of sequencing cance signifi the understand to better trying Hospital, is General Tarjinder Ph.D., Singh, unknown. currently is stress However, role the ofvictims. SPARCL1 to social resilience in suicide and of SPARCL1 individuals depressed in reduced is plasticity. Expression synaptic for developmental required is and adhesion, synaptic dictates connectivity, neuronal induces that hevin/SPARCL1, by astrocytes a protein secreted is project. One focus this in addressed to be questions tal fundamen the are These developmentCNS disease? and in neurons and astrocytes between cross-talk mediate that signals molecular the are What assembly? circuit synaptic to orchestrate interact (CNS). astrocytes How and do neurons system nervous central the in interactions astrocyte-synapse govern that mechanisms molecular the University, studying is Sandeep Singh, Ph.D., multiple datasets. across validated and replicated here rigorously be will clusters, symptom anxiosomatic vs. responsible for improvement circuits dysphoric in distinct two yielded identified which Prior results, TMS. using symptoms depressive responsible for improvementnections individual in con the to map connectome human the by using hypothesis this test connectivity. Dr. will Siddiqi of brain pattern cific spe their onand apatient’s symptoms based specific targets TMS personalize to ofseeks project major depression. This symptoms different to treat (TMS) stimulation magnetic non-invasive transcranial with stimulated selectively and mapped be can circuits brain how distinct understand better M.D., Siddiqi, Shan behaviors. depression-like expresses and neurons in DNA deletions mitochondrial develops genemutant that polg a expressing line mouse model, atransgenic mouse polg the in neurons from healthy sible differently behave neurons disorder-respon how bipolar address Thewill model. work of a BD animal brain BD-responsible the in neurons vidual indi by accessing sensitivity of high physiology BD with patho the to detect analyses apply single-cell project will disorder. bipolar This of people with phenotypes and genetics both recapitulate that models animal with working is Japan, Yasuyuki Ph.D., Shima, Therapies Next-Generation Basic Research Basic Basic Research Basic Harvard Medical School, aims to School, aims Medical Harvard Harvard University/Massachusetts Harvard RIKEN Brain Science Institute, Institute, Science Brain RIKEN Virginia Commonwealth Commonwealth Virginia ------cellular and molecular level that was previously inaccessible. previously was that level molecular and cellular at aclose studied be then can which disorders, psychiatric of neuro diagnosis for their basis genetic who aclear have patients from derived organoids brain to study them allows also platform This system. culture organoid brain 3D human lab’s the in neurons with interact develop and how glia stand Steven M.D., Sloan, variation. protein-coding of ultra-rare presence the in risk of polygenic tions common contribu the to clarify Biobank UK the and consortium theSCHEMA like efforts sequencing by large generated data thegenetic use will project This unknown. remains risk treat neuropsychiatric disorders. neuropsychiatric treat receptor to insulin astrocytic the of targeting possibility the exploreis to the research of aim ultimate The homeostasis. for proper imperative brain are which astrocytes, the type, cell brain on another action on insulin focus will research this abnormalities; metabolic display neurons in receptor (IR) insulin the lacking Mice disorders. mental many in observed deficiencies cognitive in implicated be also may and eases dis neurodegenerative present in are system nervous central the in disturbances insulin-signaling that indicated has Evidence mood. and cognition including processes modulate Ph.D., Solas, Maite tandem. in unfold processes two moment-to-moment the understand of how relationship these better is to here aim The on attention states. our depending changes of neurons patterns activity fine-scale the areas, sensory Within information. sensory processing areas brain other with priorities and goals our as such things resenting rep areas brain between coordination It involves large-scale disorder. mental every nearly in disrupted is attention, which Snyder,Adam Ph.D., biology, imaging, and neurobiological approaches to under approaches neurobiological and biology, imaging, cell stem next-generation sequencing, genome engineering, uses team his To questions, these schizophrenia. answer and autism like disorders in dysfunction circuit underlies development glial aberrant whether development, asks and during formation circuit neural coordinate actively glia how multi-scale brain function unfolds. The focus will be will Thefocus unfolds. function brain how multi-scale of groups compute. neurons about The is project how small influence states large-scale that but of activity, also terns pat to large rise give neurons tiny of many interactions the Spain, is studying insulin action on the brain, which may may which brain, on the action insulin studying is Spain,

Basic Research Basic Research Basic Basic Research Basic Research Basic

University of Navarra, Pamplona, of University Navarra, Ph.D., University of Rochester, notes that of University Rochester, notes that Emory University, Emory notes that ------bbrfoundation.org 33 ------Columbia University/ Gladstone Institutes/ Harvard Medical School, notes Basic Research BasicResearch Next-Generation Therapies

tion from outside reality. fromtion This outside project willtest the assump that tion the medial prefrontal cortex is central(mPFC) in both mood and reality monitoring; if then so, modifying its activity withbrain non-invasive stimulationmethod TMS and social learning. Alterations within these cortical circuits may also underlie the auditory perceptual hypersensitivity often seen This in ASD. research aimsto harness brain’s the inherent plasticity mechanisms recovery patho promote to of logical auditory cortical circuits. The goal to is ways find of activatingthe of a subset interneurons within of layer1 (L1) auditorycortex, which past has work identified of hubs as Karuna Subramaniam,Karuna Ph.D., with schizophrenia suffer severefrom cognitive impairments such as impaired reality-monitoring. Reality-monitoring is the ability distinguish to internally self-generated informa could reveal the mechanisms through which TMS targeting the may causallyof mPFC impact mood and higher-order cognition, both in and controls in schizophrenia patients. Ph.D., Takesian, Anne andtion social interaction, surprisingly little is known about the neurobiological underpinnings the of auditory sensory symptoms the Dysregulation of disorder. neural of circuits within the auditory cortex may be particularly disruptive in asASD, these circuits the provide foundation language for gain a more complete picture of how it influencesgain it picturepresynaptichow complete of more a neurotransmissionDA in distinct dopaminergic circuits of male and female mice and the probe corresponding impact behavior. on Benjamin Suarez-Jimenez, Ph.D., Research Mental Foundation for Inc. Hygiene, NYSPI, / is interested inthe hypothesis thatPTSD ismediated dysby functional discrimination andreward processing, involving thehippocampus, accumbens, nucleus amygdala, and pre frontal cortex. Thisresearch will investigatebrain activity differences between patients half(n=30; with PTSD with and trauma-exposed depressive disorder), major controls fMRI(n=30). and a VR paradigm will be used clarify to the neural mechanisms underlying reward learning and dis crimination processing across and PTSD, whether differs it fromwork PTSD-major The can depressive disorder. shed light thebrain on specificof role areasneeded for discrimi nationlearning withinan thus environment, informing the diagnostics of development and treatments PTSD for and other psychopathologies. University of California,University of San Francisco, that notes patients that while ASD is characterized deficitsof by communica ------Columbia University, Columbia University, Ph.D., Florida Atlantic University, notes notes Florida Atlantic University, Yale University, aimsreveal to University, Yale University of Maryland, University of that notes Basic Research Basic Research Diagnostic Intervention Tools/Early

the genetic need for models that demonstrate a functional impact sexual of difference in dopamine the system (DA) relating neurodevelopmental to disease susceptibility. Such models wouldinform efforts identifyto penetrant genetic changes signaling in DA that drive risk ADHD, and for animalgenerate improved will models the She of disorder. to mutation with Val559 work a model based the on DAT tinct features brain andof disease. development focusThe will be uncover to the regulatory mechanisms that govern human-specific gene expression changes that heteroch are functional regulatory that elements human-dis govern rently in a major depressive inrently episode a major are who unmedicated. Adele Stewart, Ph.D., They will undergo two MRI sessions,at baseline whilemed ication-free and after 6–8 weeks medication of treatment. treatment response SSRI to antidepressants.team The will recruit 20 participants with depressive disorder major cur measurement cortical of GABA levels magnetic by resonance spectroscopy (MRS) determine to whether these measures in patients with of depressive group a disorder can major predict Louisa Steinberg, M.D., Steinberg, Louisa will functional conduct quantificationauditoryof responses with functional magneticresonance imaging(fMRI) and to studyto molecular changes in circuit-specific synapsedevel and plasticityopment in animal models various of human brain diseases. of a visualof system pathway that drives circadian rhythms in the mammalian brain; is called it the retinohypothalamic tract (RHT). will He use a platform that can also be used organization and activity-dependent plasticity ipRGC of connections. Speer is investigating Dr. the molecular and structural mechanisms regulatingthe formation and function brain adjust neural to circuits the to light cycle. the Despite importance circuits regulating for ipRGC of mood, circa and littlediansleep, is knownphysiology, theabout synaptic Colenso Speer, Ph.D., Speer, Colenso retinalphotosensitive ganglion in the retinae cells (ipRGCs) transmit luminanceinformation subcortical to targets in the cell types. The aim revealto is regions reguwhose genome latory potential may explain differences in gene expression observed between species. during prenatal development. To do so, Dr. Sousa will Dr. so, do during prenatal To development. simultaneouslyassess theregulatory potential all of areas theof human in single genome, neurons, glia, and other ronic, i.e., occurronic, i.e., in different temporal sequencehumans, in Andre Sousa, Ph.D., Sousa, Andre 34 Young Investigator Grant Program 2019 The team will also explore whether regulation differs by differs explore regulation whether also will The team PNS for SNS and functioning. markers chophysiological andpsy HPAtreatment on axis of effects to examine is aim The treatment. through progress victims youth how predicting in utility to their eye an with services, trauma in enrolled abuse sexual of child youth victims outcomes among or psychophysiological physiological on related focuses project This trauma. to early exposed populations child (PNS) among system nervous pathetic (SNS), system parasym and nervous sympathetic the as well as (HPA) axis, adrenal pituitary hypothalamic the system, stress major neuroendocrine the across tioning func in disruptions shown have studies past notes that Ashwini Tiwari, Ph.D., Tiwari, Ashwini who are followed up longitudinally and who completed have and up followed longitudinally who are of ~167,000 study cohort a large from data lyzing participants ana by theories. First, several test will project This disease. due to heart are that patients in of death rates of increased causes the specifically disease, cardiovascular and phrenia schizo between relation the understand to better wants Treur,Jorien Ph.D., at a 3-month follow up. and treatment, prior following time-points: to treatment, at three made be will Assessments treatment. to trauma non-responders and responders youth gender, between and (MRI). imaging resonance magnetic on changes psychosis-related observable with compared be also will features linguistic The over time. change symptoms how help psychosis predict they whether and functioning, and cognition, symptoms, clinical reflect meaningfully features these whether test over time).will morebecome They similar conversation partners between (how speech accommodation Sunny Tang, M.D., of connections. promote re-wiring that the plasticity ing of words conform to expected patterns), and acoustic patterns), acoustic and to of expected words conform ing (how coherence sequenc speech), tone semantic in during (proportion of words), unique complexity prosody (changes rate), fluency (speech including features language measure to symptoms psychosis people young with in analyses tic automated linguis use will team the psychosis, for tracking avenue optimal an provides language that Suggesting brain. the in changes disease-related tracking efficient way of and asensitive we need phase, prodromal the during ticularly par of illness, course the in early disorders psychotic related and schizophrenia in interventions order in to target that Diagnostic Tools/Early Intervention Diagnostic Tools/Early Intervention Diagnostic Therapies Next-Generation Basic Research Basic

University of Amsterdam, Netherlands, Netherlands, of University Amsterdam, University of Pennsylvania, proposes proposes of University Pennsylvania, McMaster University, Canada, University, Canada, McMaster

------determination of the specific impact of the SCN theon SCN mood, of impact specific of the determination allow will This firing. SCN to manipulate of optogenetics use though behaviors, psychiatric-related regulate rhythms activity neural SCN whether to determine seeks project This behavior. anxiety-like and of depressive regulation the in brain, the in nucleus (SCN), pacemaker the suprachiasmatic arole uncovered for the has Her team unclear. are anisms mech but underlying the disorders, anxiety and mood in role a causal have they suggest studies Animal anxiety. and of depression etiology involved the or in are symptoms ring simply co-occur are disturbances circadian whether address Chelsea Vadnie, Ph.D., disease). cardiovascular instance, outcome(forvariable certain on a effects proxy, causal to test or instrument, an as schizophrenia) (forvariable instance, risk of acertain predictive robustly are that variants genetic one or more uses MR risk. disease cardiovascular and phrenia to schizo liability between of associations nature causal the to test (MR) randomization Mendelian by applying and use; medication health, mental on their questionnaires extensive major depression and become a therapeutic option, atherapeutic particu major become depression and treatment theof intervention for effective well-tolerated and prove asafe, to be over will and 60 patients in stimulation group). TBS sham that (called The is treatment hope placebo Leandro Valiengo, M.D., symptoms. depressive and connectivity brain functional both in changes precede responses mood abnormal that hypothesis the test will depression. She subclinical and clinical with adolescents in scans brain (fMRI) imaging resonance magnetic functional resting-state longitudinal and collection, data phone-based smart and online- modeling, combination of computational a use She will changes. to environmental adapting in cits defi outcomes depression explain in negative to positive and responses mood abnormal whether project to determine is this of behavior.goal The successful role regulating of in mood about the known is little that observes London, UK, College Vaghi, Ph.D., Matilde regions. brain other in or clocks SCN the target that strategies of treatment feasibility the mine It help deter could behaviors. anxiety-related and cognitive, to receive either a TBS treatment (called TBS group) TBS or a (called treatment either aTBS to receive elderly. assigned randomly be of Asample 108 will subjects rTMS the in of major disorder treatment depressive the in theta-burst of efficacy the to evaluate trial ble-blind clinical dou controlled, arandomized, perform will Paulo, Brazil,

Basic Research Basic Basic Research Basic Research Basic University of London/University of University London/University University of Pittsburgh, will will of University Pittsburgh, Ph.D., Universidade de São Universidade ------bbrfoundation.org 35 ------Houston Methodist Research Research Methodist Houston Icahn Medicine School of Mount at National Institute Alcohol on Abuse University of California University of San will Diego, Basic Research Basic Research Next-Generation Therapies

erated by activated genes. Dr. Weng’s goal is understand to erated activated by Weng’s genes. Dr. and m6A DDX3X how residues engage neuronal mRNAs and whether this modulates synaptic function. team’s The & Alcoholism, NIH, explains that a ketogenic diet (KD; high in fat and in carbohydrates) low increases bodies ketone beta-hydroxybutyrate and acetone acetoacetate, including in plasma(BHB) and a state metabolic brain of ketosis). (i.e., KD has been proposed as a therapeutic psy intervention for chiatric disorders, including mood disorders In and epilepsy. rat models alcohol of dependence, a KD has been shown to improve withdrawal symptoms during alcohol detoxification, Yi-Lan Weng, Ph.D., regulationscriptomic in the brain as may inform it neurode disordersvelopmental such as This ASD. regulationof layer refers set the chemical to of complete changes that impact the transcriptome, which is the total set “messages” of gen main will approach utilize be to cutting-edge human induced stem cell pluripotent models focus to defining on of roles the signalingm6A-DDX3X axis neuronal on function. Corinde Wiers, Ph.D., Lu Wang, Ph.D., createhuman brain organoids, generated frompatients with inmutations called a gene ACTL6B, understand to in its role and theneurodevelopment pathogenesis The lab ASD. has of already clinically characterized families 253 having least at child one diagnosed with in six ASD, which, of variants in ACTL6B encoding associated were BAF53b with The ASD. working hypothesis is that functional ACTL6B loss of leads a dysfunctionto activity-dependent of chromatin accessibil ity during brain causing development, altered expression of ASD-relateddendrite-genesis and/or related genes, ultimately perturbing cellular fate. Allison Waters, Ph.D., Sinai, notes that advancesin white matter imaging have mapsprovided the of brain whose great detail explain help the difficultyprecision-targeting of atreatment like deep brain stimulation a method that (DBS), surgically involves implantingelectrodes deep within specific brain areas such as a large and white matter complex bundle fiber called the limbanterior the of internal capsule (ALIC), promising a target treat This to DBS for project OCD. seeks developto electrophysiological the read-outa patient-level, of cortical response specific at DBS to white matter targets within the ALIC. probe to is be The validatedon level of the individ uals, which could allow individualized for “tuning.” DBS Institute,seeks advance to our understanding epitran of ------University of Milano University of Memorial Sloan-Kettering McGill University, Canada, McGill University, asks: Basic Research

Next-Generation Therapies Diagnostic Intervention Tools/Early Next-Generation Therapies Cancer will Center, use stem cell technology study to neu ronal pathologies intel related neurodevelopmental to (e.g. pendent, neurosciencependent, and clinical to in order psychology, increase the effectivenessof a short psychotherapeutic inter will She vention. test an integrated approach which com bines the noninvasive brain stimulation called transcranial direct current stimulation with (tDCS) anevidence-based Bicocca, seeks two Italy, combine to fields apparently inde throughout the body. Preliminarythroughout the body. research suggests the BAF iscomplex especially important regulating for a specific subset genesof that are activated signals by from the environment. lectual a specific of disability/autism. is a component Arid1b molecular machine called the BAF which complex, is involved in the process turning of specific on genes off and in cells bipolar disorder) conditions. Thesebipolar disorder) experiments designed are characterizeto the function a gene, called of which Arid1b, is among the most in frequently mutated children with intel lectual disability, and autism) psychiatric schizophrenia, (e.g. Thomas Vierbuchen, Ph.D., Vierbuchen, Thomas treatment. will She start with focused a representative project patientson the with clinical depressive disorder, major sample in whichboth MCT and tDCS be to effective. have proven could be experimentallyhowever, protocol, The extendedto other disorders such as anxiety and craving. (MCT). will Patients be invited take to part in an experimen tal treatment; protocol symptomatology will be tested four at different timesto evaluate the effectiveness ofintegratedthe psychotherapeutic intervention called metacognitive therapy tionalbrain statesthat diagnosticmap onto sup a outcomes, thatposition will be tested in this project. Alessandra Ph.D., Vergallito, includes infants are who risk high low at or familial risk because an sibling has older received an autism diagnosis.team The will techniquesapply that capture subtle dynamicpatterns in brain activity,resulting in profiles, detectable as early months. 3 as These suggest thatvery early EEG markersreflect altered func The team The will integrate data collected in the three largestautism cohorts in resulting the world, EEGs 1400 (electroen in over cephalograms) than from more 400 infants. This repositoryEEG Stefon van Noordt, van Stefon Ph.D., are there distinct patterns brain of activity during infancy that reliably predict future proposes autism that He outcomes? the dynamics the of brain in early infancy can serve this function. larly useful patients for withpoor response contraindica or tions the to use antidepressants.of 36 Young Investigator Grant Program 2019 oped means to simultaneously image the enzyme GTPase GTPase enzyme the image to simultaneously means oped Switzerland, hopes to gain an understanding of neuronal of neuronal understanding an to hopes gain Switzerland, Zachary Wills, Ph.D., Wills, Zachary PTSD. in extinction fear enhance can amygdala of (DES) the stimulation electrical direct whether time first for the to test PTSD, and with patients in task extinction and acquisition afear during hippocampus and amygdala human the in responses neurophysiological acterize to char aims Dr. Hospital, University Willie group at Emory research PTSD established an and country the in programs surgery epilepsy one largest of the between a collaboration non-response. In treatment and symptoms of PTSD tenance development main and predicts hyper-reactivity amygdala that suggesting results imaging Hospital, notes functional M.D, Willie, Jon behavior. tory audi contribute to goal-directed cell-types of corticostriatal Ph.D., Williamson, Ross S1. in LTP mechanisms GABAergic-dependent underlying alters downregulation SHANK3 how ASD-implicated reveal project, to this in used be will model amouse Such SHANK3. mutation for ahomozygous carrying models animal in duced repro are symptoms some autistic of and some autism, forms in implicated been has protein SHANK3 scaffolding synapse excitatory The function. interneuron on GABAergic depends plasticity, aphenomenon strongly synaptic into that altered translate may dysfunction GABAergic that hypothesis the (S1) explore will for of model ASD. amouse Dr. Williams cortex somatosensory the in plasticity and function network Ph.D., Williams, Leena avenue. possible therapeutic order to explore this dis use alcohol with drinkers heavy non-treatment-seeking in design crossover two-way supplement, arandomized and anutritional (KE), ketone aone-dose ester with tion study is a interven project pilot This intake. alcohol reduce and costriatal cell-types; and describe how distinct populations populations how distinct describe and cell-types; costriatal corti distinct modulate can state of behavioral biomarkers known how test will research (SCN). This sub-cerebral and (ITN) intratelencephalic cortex: auditory primary the in cell-types main input long-range two from receives tum stria The schizophrenia. in deficits auditory underlying mechanisms neural of the understanding provide abetter to striatum, to the cortex auditory the from of information flow about the questions addressing conduct experiments Therapies Next-Generation Next-Generation Therapies Next-Generation Basic Research Basic Research Basic Ph.D., University of Pittsburgh, has devel has of University Pittsburgh, Emory University/Emory University University University/Emory Emory University Hospital of Geneva, of Geneva, Hospital University University of Pittsburgh, will will of University Pittsburgh, ------of depression. models animal exploredin be will This symptoms. alleviate might connections these restoring and strengthening that depression and in altered are regions brain to downstream the SUB of connections the that sion. hypothesize They depres for in intervention target apotential as SUB the address will Dr.volume SUB. of Wozny the colleagues and the in reduction fromshow depression a significant suffering (SUB). subiculum the Patients called formation pocampal hip of the overlooked part an studying is UK, Scotland, Wozny,Christian Ph.D., M.D., pathology. disease to reverse targets novel pharmacological potentially identify and of schizophrenia origins cellular to uncover are aims ultimate The to schizophrenia. by GWAS studies linked are 7, (GEFs)factors Trio, 9 and genes Kalirin encoding whose nucleotide exchange guanine activators, GTPase of three function the approach to characterize imaging-based sensor this use will project This neurons. of pyramidal dendrites in RhoA GTPase for the anovel to uncover function team his enabled advance technological This modulators. calcium and regulators of GTPase function the of characterizing a means offering neurons, developing in sensors calcium and pioneered advanced non-invasive fetal magnetic resonance resonance magnetic non-invasive fetal pioneered advanced Dr. period. Wu’s fetal the in has begin may team CHD in dysfunction neurobehavioral suggests Evidence repair. cardiac neonatal despite successful difficulties social-behavioral and long-term learning experience of CHD Survivors distress. (>60%) psychological prevalence of prenatal high alarmingly Yao Wu, Ph.D., responses. coping modulates which DRN the from arising architecture circuit long-range and local the as well as responses coping active driving in neurons GABAergic serotonergic, and glutamatergic, roles of DRN causal the Dr. to elucidated. be Wright to dissect remain plans subtypes, neural many containing nucleus heterogeneous complex and a DRN, the within responses coping drive which types cell However, evidence. the clinical and ofon basic multiple lines based to stress, responses coping coordinating node in central a to be thought is neurons, serotonin forebrain-projecting of source main the raphe (DRN), nucleus dorsal the that Ph.D., M.D., Wright, Matthew fetal diagnosis of coronary heart disease (CHD) suggest an an (CHD) suggest disease heart of coronary diagnosis fetal Dr.comes. Wu’s a women with pregnant in pilot studies out health child and on maternal stress pregnancy-related of impact the studying is Institute, Children’s Research

New Technologies New Basic Research Basic Research Basic Children’s National Medical Center/ Children’s Medical National University of Strathclyde, ofUniversity Strathclyde, Stanford University,Stanford notes - - - bbrfoundation.org 37 ------University of North University of Carolina National Institute Drug on Abuse, University of Texas Southwestern University Texas of Basic Research Basic Research BasicResearch

ants anorexia for nervosa. Converging lines evidence of suggest that anorexia nervosa patients with high levels of obsessive-compulsive symptoms and perfectionism could be a clinically distinct and the group, goal this of study is examine to the geneticarchitecture obsessive-compulsive of and perfectionism symptom dimensions in patients with Ph.D., Jun Yokose, Medical Dallas, at Center is interested in observational learn ing, the ability learn to through observing experience. others’ Previous human studies suggest that individuals with ASD have difficultyprocessing in the information between specific actions performed the by self and observing the matching actionsperformed others. by This tests project hypothesis the crete sCBs canonical for and non-canonical targets receptor in vitro and commonly for reported physiological effects (i.e., cardiovascular and hallucinogenic activities) in vivo. Zeynep Yilmaz, Ph.D., nervosa, an eating and obsessive-compulsive disorder, symp toms.Recent research has uncovered eight genetic risk vari anorexia nervosadetermine to whether these symptoms also form a biologically distinct within subgroup anorexia nervosa. YilmazDr. will leveraging existing genetic data from the Psychiatric Genomics Consortium Eating Disorders Working patients with anorexia nervosa and ~56,000 (~17,000 Group and a separate anorexia datasetcontrols), comprising 1,374 nervosa patients. cohort of recent-onset psychosis patients (ROP), the team psychosisrecent-onset cohort of patients (ROP), will study epigeneticsignatures how identified via whole-ge analysisnome olfactory of neuronal cells sampled from TR patients correlate with clinical manifestations psychosis. of This will be the firsttoward step identifying biomarkers to quantitatively assess treatment-resistant psychosis. Ph.D., Hideaki Yano, leadinghave emerged as problem a major a high to occurrence emergencyof visits, room particularly among young people. sCBs are categorically differentphytocannibinoids from like cannabis andcause an arrayundesired of symptoms rarely triggeredcannabis, by including hallucinations, disorienta hypothermia,tion, catalepsy, coma, and even death. Some theof adverse effectsobserved in patientsresemble sero tonin(5-HT)-mediated effects. project This willaddress the 5-HT1A receptor (5-HT1AR) interaction in particularsince hypothermia and catalepsy are the hallmarks 5-HT1AR- of mediatedYano effects. will Dr. also evaluate structurally dis NIH, is focusing synthetic on cannabinoids which (sCBs) at Chapel at Hill, is focusing theon intersectionanorexia of - - - - University of Texas Health University Texas of Science Albert EinsteinCollege Medicine, of Johns Hopkins University School of Basic Research Basic Research New Technologies

Next-Generation Therapies Johns Hopkins Schizophrenialongitudinal (JHSZC)’s Center Kun Yang, Ph.D., Yang, Kun hypersensitivity sensory to stimuli and social deficits in mice that model Fragile X syndrome, a genetic disorder with some similarities autism to spectrumdisorder. in sensory experience-dependent synapse remodeling; and examine whether impaired autophagy is causally related to understand sensory how induces input synaptic remodeling. This project willtest whetherautophagy—the process in which cells eliminate dysfunctional components—is involved hypersensitivity sensory to stimuli in adulthood, seizure, and deficits in social behaviors associated withautism, schizophre nia, and other neuropsychiatric wants Yan disorders. to Dr. Jingqi Yan, Ph.D.,Jingqi Yan, amus (PVH), a brain region important in homeostatic reg ulation, including feeding and physiological adaptions for survival; and the lateral septum (LS), implicated in relevant psychiatric disorders, including anxiety disorders and stress. Thisproject, in an animaltestsmodel, hypothesis the that the glutamate-releasing PVHMC4R-LSv neurocircuit is a sharednovel neural pathway controlling for feedingand states. emotional anxiety-related Center at Houston, who is who studying Houston, at Center eating disorders, takes a lead from recent studies which have suggested that a commonneural pathway in the brain regulates feeding and anxiety disorders: theparaventricular hypothal of nucleus Yuanzhong Xu, Ph.D., Xu, Yuanzhong psychological distress reduction in pregnant carrying women fetuses with a diagnosis CHD; of and examine to the impact thisof brain intervention on growth in CHD fetuses using advanced volumetric MRI. 3D imaging (MRI) techniques study to brain in utero develop In this ment. study pilot the team aims examine to the impact a prenatalof cognitive behavioral therapy intervention on notes thatnotes during the critical period brain of development, sensory stimuli induce remodeling corticalof synapses by eliminating synapses some while strengthening others. Deficits sensory-dependent of synaptic remodeling are thought underlie to the delayed maturation synapses, of Medicine, will test the hypothesis that treatment resistance (TR) in psychotic disorders is associated with epigenetic mechanisms and that epigenetic study a genome-wide using neurons from TR patients in comparison with those from patients and healthy controls may be annon-TR effective address to approach this question. Taking advantage the of 38 Young Investigator Grant Program 2019 testing technology for noninvasive control of neural circuits circuits control for of noninvasive neural technology testing systems. They will test the theory that chronic, butchronic, notacute, that theory the test will They systems. valence negative tion-induced improvement and cognitive in stimula novel circuit about this gaps knowledge address will neophobia. and Dr. behavior avoidance Yun’smalizing team nor mice, female and male both in antidepressive (DG)—is dentate gyrus hippocampal (Ent) the and cortex entorhinal the Ent-DG, connecting called circuit of aneural stimulation Yun, D., Ph. Sanghee psychosis.and of depression, symptoms anxiety to future relates how this and savoring, using to reward reactivity brain to alter ability the impact adolescence in symptoms anhedonia whether investigate also She circuitry. will reward brain in nectivity con and activation enhances of stimulus apositive savoring whether to examine fMRI Dr. use Youngto rewards. will reacts how brain the changes fornovel anhedonia treatment explore component oneto whether aims this project of This effects. long-lasting generate and to intervene period optimal Young,Katherine Ph.D., applications. for human guidelines work to provide is key this in hope This receptors. neuronal modifying by genetically enhanced substantially be may to ultrasound sensitivity that hypothesis notion the from of follows sonogenetic receptors The ultrasound. to populations neuronal specific to sensitize sonogenetic receptors introduce and parameters stimulation ultrasound Dr. Yoo to brain. optimize the in action seeks of mechanism its understand to seeks project precision. This spatial millimeter with regions deep-brain in activity of neural to provide non-invasive potential control the has tion (UNM) neuromodula Ultrasonic sonogenetics. and ultrasound using Sangjin Yoo, Ph.D., mice. ASD in impairment behavioral the hope of the rescuing in cells implicated activate to artificially and mice, model ASD control and in grooming observational and self-grooming both during active tions popula neuronal Dr. Yokose to identify individuals. seeks ASD in learning observational of cognitive impairment an in result may representations of neuronal adysfunction that cence, these reward systems are still maturing, offering an offering maturing, still are systems reward these cence, adoles In events. positive experience people and anticipate how including brain’s of systems, the reward aspects late” to “upregu aims of schizophrenia—that depression and symptom aprime reward, and of pleasure pursuit the in est of loss inter for anhedonia—the treatment anew studying Children’s Hospital of Philadelphia, has found that found found that found has Children’s of Hospital Philadelphia, Next-Generation Therapies Next-Generation New Technologies New Basic Research Basic California Institute of Technology, Institute is California University of University Pennsylvania/ King’s College London, UK, is is London, UK, King’s College ------cessing of negative feedback and reward information, and and information, reward and feedback of negative cessing pro the underlying mechanisms circuit to elucidate neural the two contributes to the generation of generation states. depressive contributes to the two the between imbalance an that is The hypothesis aversive stimuli. by other the and stimuli by appetitive oneneurons, activated of BLAFezf2 populations distinct on two concentrate will Dr. conditions. Zhang or contribute disease to behavior tially differen may of which each of neurons, populations neous heteroge functionally contains which BLA, the studying in to overcome challenge is the Amajor aim stimuli. rewarding by aversive and driven behaviors role regulating in essential an plays which (BLA), amygdala basolateral on is the focus depression. The in disrupted are circuits how these determine Xian Zhang, Ph.D., “recalibaration.” circuitry hippocampal counterproductive and to avoid how to promote effects to learn is antidepressive aim cells). The overall granule DG mature (new vs. neurons outputs postsynaptic their Ent inputs and between tivity connec synaptic the modulates Ent-DG stimulation circuit

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