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1 Research Report Psychiatry and Psychology

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3 Department Chairs TABLE OF CONTENTS 2 Introduction 4 Clinical Disorders Left to right: Clark, Frye, Kung Mark A. Frye, M.D. (Chair, Rochester, Minnesota) Matthew M. Clark, Ph.D. (Chair of Research) Simon Kung, M.D. (Vice-chair of Research) 16 Novel Methods for Understanding 20 Novel Methods for Intervening 24 Medical Diseases Interface with Psychiatry and Psychology 44 Science of Health Care Delivery 46 Career Development 53 Resident and Fellow Researchers 59 The Research Psychometrics Resource Teresa A. Rummans, M.D. (Jacksonville, Florida) 60 Research Study Team Cynthia M. Stonnington, M.D. (Scottsdale, Arizona) Kristin Vickers Douglas, Ph.D. (Chair of Education) Brian A. Palmer, M.D. (Vice-chair of Education) 1

4 Welcome to the Research Report of the Mayo Clinic Department of Psychiatry & Psychology Thank you for your interest in our Department of Psychiatry and Psychology and learning more about our recent research accomplishments. Our department plays an essential role in Mayo Clinic s goal of inspiring hope and contributing to health and well-being by providing the best care to every patient through integrated clinical practice, education, and research. At Mayo Clinic s three main campuses -- Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona -- there are over 150 psychiatrists and psychologists, joined by over 200 allied health staff to meet the needs of the patient. Our flagship clinical programs include our Psychiatric Hospital, Mayo Clinic Depression Center, Pain Rehabilitation Program, Addiction Treatment Center, Child and Adolescent Programs, Neurocognitive Assessment and Treatment Programs, Behavioral Medicine Program, and Integrated Care Programs. Our department provides numerous educational programs including Graduate Medical Education residencies in Adult and Child and Adolescent Psychiatry, fellowships in Medical Psychology (Clinical Child Psychology, Clinical Health Psychology, and Clinical Neuropsychology), Geriatric Psychiatry, Psychosomatic Medicine, Sleep Medicine, and Addiction Psychiatry. Due to the expertise and range of these clinical and educational programs, our Department of Psychiatry and Psychology was ranked as one of the Top Ten Psychiatry Departments in the country by the U.S. News and World Report in Many of our research projects focus on clinical interventions and our clinical programs guide and shape our research efforts, which in combination seek to provide the best care to every patient every day. The Department of Psychiatry and Psychology continues to highlight research teams in our annual departmental research report. We want to highlight the value, importance, and productivity of research teams within our department. These research teams can also be found across the Mayo Clinic sites which include Minnesota, Florida, and Arizona, and also involve the many hospitals that comprise the Mayo Clinic Health System. For example, the Neuropsychology, Aging, and Cognition Research Team has scientific investigators across all three campuses. Research teams within our department include an array of health care professionals and focus on the evaluation and treatment of a range of mental health problems and their impact on patients and their families. The Mayo Clinic Depression Center Research Team, which includes psychiatrists, psychologists, nurses, and social workers, conducting clinically relevant research in treatment-resistant depression and bipolar disorder, is an example of a highly productive multidisciplinary clinical research team. Additionally, many investigators in our department are engaged in research projects with other departments or centers of excellence across our academic medical center. Our department has investigators in The Mayo Clinic Comprehensive Cancer Center, The Bariatric Surgery Center of Excellence, and The Alzheimer s Disease Research Center. Finally, we encourage the participation of research with other academic centers, collaborations, and multisite studies. The University of Minnesota, the Karolinska Institute in Sweden, and the National Network of Depression Centers are outstanding examples of collaborative multicenter research projects. If you are interested in contacting any of the investigators highlighted in this report, please contact our department at DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

5 In 2014, our Department had 27 funded grants where the Principal Investigator was a faculty member in our department. We also contributed to a significant number of funded studies as co-investigators across numerous departments at Mayo Clinic. The wide portfolio and funding sources in our Department include: Agency for Healthcare Research and Quality Center of Medicare and Medicaid Services National Cancer Institute National Institute on Aging National Institute of Alcohol Abuse and Alcoholism National Institute on Drug Abuse National Institute of General Medical Science National Institute of Mental Health Meeting the needs of underserved populations and addressing health disparities is a priority of our department s clinical, educational, and research programs. To address the problem, our department has numerous academic and research projects focused on meeting the needs of underserved populations, developing creative mental health treatment delivery systems, and tailoring interventions for specific underserved populations. Many people with mental health issues struggle to get needed medical, psychiatric and psychological care. Specific examples include: Expanding access to cognitive behavioral therapy (CBT) for childhood anxiety disorders via smartphones. Funded by the National Institute of Mental Health. Principal investigator: Dr. Stephen Whiteside. Family cancer literacy to promote mammography screening among Navajo women. Funded by the National Cancer Institute. Principal Investigator: Dr. Christi Patten. Healthy immigrant families: Working together to move more and eat well. Funded by the National Heart, Lung and Blood Institute. Coinvestigators: Drs. Bridget Biggs, Matthew Clark, and Christi Patten. Community intervention to reduce tobacco use among pregnant Alaska Native women. Funded by the National Cancer Institute. Principal Investigator: Dr. Christi Patten. National Network of Depression Centers. Principal Investigator: Dr. Mark Frye. Primary Care Initiatives: Coordinated Anxiety Learning and Management (CALM), Diabetes, Cardiovascular Disease, Depression, Comprehensive Pediatric and Adolescent Support Services Care Team (ComPASS), Early Management and Evidence-Based Recognition of Adolescents Living With Depression (EMERALD), and Depression Improvement Across Minnesota, Offering A New Direction (DIAMOND) Drs. David Katzelnick and Mark Williams

6 Mayo Clinic Depression Center ADULT INVESTIGATORS Renato D. Alarcón, M.D., MPH, William V. Bobo, M.D., MPH, Mark A. Frye, M.D., Astrid A. Hoberg, D.N.P., Theresa E. Hurne, LICSW, Simon Kung, M.D., Maria I. Lapid, M.D., Katherine M. Moore, M.D., Mary J. Moore, R.N., Kathleen A. Poppe, R.N., Randall L. Stone LICSW, Susannah J. Tye, Ph.D., Marin Veldic, M.D., Nicole D. Borrenpohl, M.S.N., R.N., C.N.P. Third row, left to right: Tye, Stone, Frye, Borrenpohl, Kung Second row, left to right: Daily, Moore, K, Fuhrmeister, Hoberg, Moore, M Front row, left to right: Croarkin, Bobo, Hurne, Rosenblad PEDIATRIC INVESTIGATORS Paul E. Croarkin, D.O., John E. Huxsahl, M.D., Jarrod M. Leffler, PhD, Jennifer L. Vande Voort, M.D. Depression is a significant public health problem, in this country and across the globe. Effective treatment can be challenging to identify for the individual and relapse is common after depression treatment. Therefore effective, individualized, long lasting treatments are needed for depression. The main focus of the Mayo Clinic Depression Center is to conduct clinically relevant research in treatment-resistant depression and bipolar disorder, in adults, adolescents and children. Our current research projects aim to build on our comprehensive and multidisciplinary depression treatment programs. Mayo Clinic Depression Center is a Center of Excellence for the National Network of Depression Centers, a network of 21 leading clinical and academic Centers of Excellence in the U.S. working to transform the field of depressive illness and related mood disorders. GRANTS National Institute of Mental Health RO1MH H-MR Spectroscopy of Bipolar Depression Before & After Lamotrigine Treatment. Frye (PI) 07/ /2014. To Identify baseline MR glutamate / glutamine abnormalities in bipolar depression and evaluate whether these predict treatment response to lamotrigine. Myriad/Rules-Based Medicine A Feasibility Study to Develop a Biomarker Signature in Mood Disorders. Frye/Biernacka (PI) 09/ /2014 This feasibility study will be looking at discovering proteomic platforms to identify serum samples from patients with mood disorders and controls. 6 4 DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY AssureRX A pharmacokinetic/pharmacodynamic Genetic Variation Treatment Algorithm versus Treatment as Usual for Management of Depression. Frye (PI) 07/ /2016. Evaluate clinical value of genotyping. Microbiome CIM Florida The Microbiome of Depression. Frye/Richelson, (Pis) 07/ /2016. Evaluate feasibility of testing microbiome in depression before and after treatment. Janssen Research and Development, LLC A Double-Blind Randomized Placebo-Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Major Depressive Disorder Including Suicidal Ideation in Subjects at Imminent Risk for Suicide, Frye (PI) 05/ /2015.

7 KEY PUBLICATIONS Altinbas K, Ozerdem A, Prieto ML,m Fuentes ME, Yalin N, Ersoy Z, Ayedmir O, Quiroz D, Oztekin S, Geske JR, Feeder SE, Angst J, Frye MA. A multinational study to pilot the modified Hypomania Checklist (mhcl) in the assessment of mixed depression. J Affect Disord 2014 Jan; : Doi /j.jad Calabrese JR, Frye MA, Yang R, Ketter TA, for the Armodafinil Treatment Trial Study Network. Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: A randomized double-blind, placebocontrolled, multicenter trial. J Clin Psychiatry 2014 Jul 22 [Epub ahead of print] Croarkin PE, Nakonezny PA, Husain MM, Melton T, Buyukdura JS, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for Increased Glutamatergic Cortical Facilitation in Children and Adolescents With Major Depressive Disorder. JAMA Psychiatry Jan 9:1-9. Fuentes Salgado ME, Sutor B, Albright RC, Frye MA. Every reason to discontinue lithium. Int Journal Bipolar Disorders, 2014 in press. Frye MA, Blier P, Tye, SJ. Concomitant benzodiazepine use attenuates ketamine response: Implications or large scale study design and clinical development. J Clin Psychopharmacology 2014, in press. Frye MA, Prieto ML, Bobo WV, Kung S, Veldic M, Alarcon RD, Moore KM, Choi D-s, Biernacka JM, Tye SL. Current landscape and unmet needs for treatment of bipolar depression. J Affect Disorder, 2014 in press. Kung, S, Alarcon RD, Williams MD, Poppe KA, Moore MJ, Frye MA. Comparing the Beck Depression Inventory-II (BDI-II) and Patient Health Questionnaire (PhQ-9) depression measures in an integrated mood disorders practice. J Affect Disord Mar 5;145(3): Rasmussen KG, Hanson AJ, Frye MA, Galardy CW, Kung S, Lapid MI, Lineberry TW, Palmer BA, Ritter MJ, Schak KM, Sola CL. Serial Infusions of low-dose ketamine for major depression. Journal of Psychopharmacology AWARDS AND LEADERSHIP ROLES Renato D. Alarcón, MD, MPH. Co-Editor, Archivos de Psiquiatría, Madrid, Spain; Associate Editor, Asia-Pacific Psychiatry; Associate Editor, Transcultural Psychiatry. Renato D. Alarcón, MD. MPH. Member, Board of Directors, World Association of Cultural Psychiatry. Renato D. Alarcón, MD. MPH. Workgroup member, DSM-V Committee, American Psychiatric Association. Mark A. Frye, MD. Scientific Reviewer. Member, NIMH Interventions Committee for Adult Disorders (ITVA), 2013 Present. Susannah J. Tye, Ph.D., Co-Chair. Treatment Resistant Depression Task Force, National Network of Depression Centers. Mark A. Frye, MD. Member, Scientific Advisory Board, Depression and Bipolar Support Alliance. Simon Kung, MD. Recipient of a Mayo Clinic Individual Award for Service Excellence, PROFESSIONAL INTERNATIONAL PRESENTATIONS World Psychiatric Association s XVI World Congress of Psychiatry, September 14-18, 2014, Madrid, Spain. Symposium Chair: Cardiovascular Disease and Obesity in Bipolar Disorder: Translational Research Focused on Epidemiology and Genetics Mayo Clinic Bipolar: Focus on Metabolic Disorders. CLINICAL DISORDERS

8 Neuromodulation Research Group: Electroconvulsive Therapy, Transcranial Magnetic Stimulation, And Deep Brain Stimulation From left to right: Fields, Tye, Frye, Lee INVESTIGATORS Sarah K. Brown, PA-C, Ron I. Citronowicz, PA-C, Paul E. Croarkin, D.O., Stacy L. Farrow, R.N., C.N.P., Julie A. Fields, Ph.D., Mark A. Frye, M.D., Michael N. Govrik, PA-C, Emily K. Johnson, D.N.P., R.N., C.N.P., Kendall H. Lee, M.D., Ph.D., Maria I. Lapid, M.D., Simon Kung, M.D., Paul H. Min, Ph.D., Brian A. Palmer, MD., Keith G. Rasmussen Jr, M.D., Debra A. Ryan, R.N., Shirlene M. Sampson, M.D., and Susannah J. Tye, Ph.D. From left to right: Min, Sampson, Citronowicz Back row, from left to right: Croarkin, Johnson, Rasmussen, Govrik, Ryan Front row, from left to right: Lapid, Kung, Brown, Farrow The Neuromodulation Research Group at Mayo Clinic in Rochester, Minnesota, has been active in performing research regarding Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS), and Deep Brain Stimulation (DBS). Dr. Rasmussen is leading a study investigating the use of daily right unilateral ultrabrief pulse ECT to potentially shorten the treatment duration of ECT for depression, without sacrificing effectiveness or cognitive impairments. Drs. Johnson and Kung are tracking real-world clinical outcomes of ECT for depression, with special attention to perceived memory impairments. Dr. Croarkin is leading a multi-site randomized double-blinded study of TMS versus sham for the treatment of adolescent depression, which will be the largest study of TMS in the adolescent population. Dr. Sampson has conducted openlabel TMS studies in patients with depression and comorbid conditions such as Post-traumatic Stress Disorder (PTSD), Borderline Personality Disorder, and chronic pain/fibromyalgia. Dr. Frye is leading a groundbreaking randomized study of DBS for treatment-resistant obsessive-compulsive disorder, in collaboration with Neurology and Neurosurgery. These examples of our neuromodulation research highlight the underlying goal: to expand our knowledge and treatment options for depression and other psychiatric illnesses, beyond conventional medications and psychotherapies. 6 6 DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

9 CLINICAL DISORDERS GRANTS Brain and Behavior Research Foundation, NARSAD Young Investigator Award. Gutamatergic Neurotransmission in Youth at Risk for Bipolar Disorder (PI: Croarkin, Mentor: Frye) 07/ /2015. NIMH Mentored Patient-Oriented Research Career Development Award. 1K23MH A1: Glutamate Probes in Adolescent Depression (PI: Croarkin, Mentor: Frye) 02/ /2018. Paul and Betty Woolls Foundation (formerly The O Shaughnessy Foundation): A Double-Blinded, Sham-Controlled Study Utilizing rtms in Adolescents with Major Depressive Disorder. Funding period: 07/ /2015; PI: Croarkin. KEY PUBLICATIONS Chopra A, Abulseoud OA, Sampson S, Lee KH, Klassen BT, Fields JA, Matsumoto JY, Adams AC, Stoppel CJ, Geske JR, Frye MA. Mood Stability in Parkinson Disease Following Deep Brain Stimulation: A 6-Month Prospective Follow-up Study. Psychosomatics 2014;55(5): Croarkin PE, Nakonezny PA, Lewis CP, Zaccariello MJ, Huxsahl JE, Husain MM, Kennard BD, Emslie GJ, Daskalakis ZJ. Developmental aspects of cortical excitability and inhibition in depressed and healthy youth: an exploratory study. Front Hum Neurosci 2014;8:669. Croarkin PE, Nakonezny PA, Husain MM, Port JD, Melton T, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. Brain Stimul 2014;7(2): Kozel FA, Croarkin PE, Mapes KS. A non-epileptiform event in the course of rtms: a case for close physician monitoring. Brain Stimul 2013;6(6): Rasmussen KG. Do Patients With Personality Disorders Respond Differentially to Electroconvulsive Therapy?: A Review of the Literature and Consideration of Conceptual Issues. J ECT 2014 (epub ahead of print) Rasmussen KG, Ritter MJ. Some Considerations of the Tolerability of Ketamine for ECT Anesthesia: A Case Series and Review of the Literature. J ECT 2014 (epub ahead of print) Rasmussen KG. Propofol for ECT anesthesia: A review of the literature. J ECT 2014;30(3): Rasmussen KG, Kung S, Lapid MI, Oesterle TS, Geske JR, Nuttall GA, Oliver WC, Abenstein JP. A randomized comparison of ketamine versus methohexital anesthesia in electroconvulsive therapy. Psychiatry Res 2014;215(2): Wall CA, Croarkin PE, McClintock SM, Murphy LL, Bandel LA, Sim LA, Sampson SM. Neurocognitive effects of repetitive transcranial magnetic stimulation in adolescents with major depressive disorder. Front Psychiatry 2013;12(4):165. LEADERSHIP ROLES Paul Croarkin, D.O. Co-Chair of Annual Meeting, Clinical Society of Transcranial Magnetic Stimulation, Shirlene M. Sampson, M.D., Executive Committee Member, International Society for ECT and Neurostimulation, 2010 present. Dare FY, Rasmussen KG. Court-approved electroconvulsive therapy in patients unable to provider their own consent: A case series. J ECT 2014 (epub ahead of print)

10 Pediatric Anxiety Disorders Research Group INVESTIGATORS Stephen P. Whiteside, Ph.D., L.P., Bridget K. Biggs, Ph.D., L.P., Mark W. Olsen, M.D., Michael S. Tiede, MA, LP, and Julie E. Dammann, MA, LP From left to right: Dammann, Whiteside, Biggs, Tiede The goal of this multidisciplinary research team is to improve the care of children and adolescents with anxiety disorders and obsessive compulsive disorder (OCD). During the past year, we completed a dismantling study evaluating the relative effectiveness of different components of CBT and an examination of anxiety treatment throughout the Mayo Clinic Health System. We are currently investigating the potential for using technology to increase access to high quality treatment for childhood anxiety disorders. This work proceeds under a grant to develop a web-based application for clinicians to interact with patients using our iphone application, Mayo Clinic Anxiety Coach, and a grant to develop an immersive video game for children with social phobia. Our team is also in the process of extending our research on intensive treatments for pediatric OCD to all pediatric anxiety disorders. Finally, we are continuing work to develop an electronic assessment system for evaluating pediatric psychiatric symptoms. In presentations and workshops were given at the annual meetings of the World Congress of Cognitive and Behavioral Therapy, the Anxiety and Depression Association of America, and the Association of Behavioral and Cognitive Therapy. GRANT National Institute of Mental Health Clinic: Expanding access to CBT for childhood anxiety disorders via smart phones (R34 MH ). Funding period: ; PI: Whiteside. National Institute of Mental Health Clinic: Games for Children with Social Anxieties (SBIR MH ). Funding period: ; Site-PI: Whiteside. KEY PUBLICATIONS Ale, C. M., Arnold, E.A., Whiteside, S. P., & Storch, E. A. (2014). Family-based behavioral treatment of pediatric compulsive hoarding: A case example. Clinical Case Studies, 13, Gryczkowski M.R., Tiede M.S., Dammann J.E., Brown Jacobsen A., Hale L.R., & Whiteside S.P. (2013). The Timing of Exposure in Clinic-Based Treatment for Childhood Anxiety Disorders. Behavior Modification, 37, McKay, D. & Whiteside S.P. (2013). Introduction to the special issue: New methods in exposure therapy. Behavior Modification, 37, DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY Nogueira, C. Y. S., Carvalho, A. M., Gauer, G. Tavares, N, Santos, R. M. M., Ginani, G., Rivero, T. S., Moraes, P. H. P., Whiteside, S. P., Malloy- Diniz, L. F. (2013). Translation and adaptation of impulsive behavior scale (UPPS) to the Brazilian population. Clinical Neuropsychiatry, 10,

11 CLINICAL DISORDERS Whiteside, S. P., Ale, C. M., Vickers Douglas, K., Tiede, M. S., & Dammann, J. E. (2014). Case examples of enhancing pediatric OCD treatment with a smartphone application. Clinical Case Studies, 13, Whiteside, S. P., Gryczkowski, M., Ale, C. M., Brown-Jacobsen, A. M., McCarthy, D. M. (2013). Development of child- and parentreport measures of behavioral avoidance related to childhood anxiety disorders. Behavior Therapy, 44, Whiteside, S. P., McKay, D., De Nadai, A. S., Tiede, M.S., Ale, C. M., & Storch, E. A. (in press). A baseline controlled examination of a 5-day intensive treatment for pediatric obsessive-compulsive. Psychiatry Research. Young, B. J., Wallace, D. P., Imig, M., Borgerding, L., Brown- Jacobsen, A. M., & Whiteside, S. P. (2013). Parenting behaviors and childhood anxiety: A psychometric investigation of the EMBU-C. Journal of Child and Family Studies, 22,

12 Rochester Epidemiologic Psychiatric Research Program INVESTIGATORS William V. Bobo, M.D. and J. Michael Bostwick, M.D. William V. Bobo, M.D. J. Michael Bostwick, M.D. The suicide research group focuses on improving suicide risk assessment and management through identifying risk factors and warning signs in high-risk clinical groups. Dr. Bostwick continues to supervise numerous residents and medical students, mentoring promising trainees as they undertake suicidology research projects. Using an Olmsted County cohort of more than 1,500 suicide attempters who received medical care after their attempts, Dr. Bostwick is investigating what proportion eventually died by suicide and what characterizes the long-term survivors compared to the dead. He leads a case-control study looking at health care visits and suicidal ideation in the year prior to completed suicide (86 cases) with the goals of identifying whether decedents had more visits than controls and whether they said or did anything during those visits that implicated future risk. He is participating in a naturalistic study looking at outcomes in more than 200 patients who have overdosed on acetaminophen, a readily available but potentially lethal over-the-counter medication. Dr. Bostwick is also involved in ongoing projects on physician suicide, transjurisdictional suicide, suicide in patients hospitalized on medical or surgical units, and the role of the Dexamethasone Suppression Test as a suicide risk indicator, using historical and current cohorts. KEY PUBLICATIONS Bailey CH, Andersen LK, Lowe GC, Pittelkow MR, Bostwick JM, Davis MD. A population-based study of the incidence of delusional infestation in Olmsted County, Minnesota, Br J Dermatol May; 170(5): PMID: DOI: /bjd Foster AA, Hylwa SA, Bury JE, Davis MD, Pittelkow MR, Bostwick JM. Delusional infestation: clinical presentation in 147 patients seen at Mayo Clinic. J Am Acad Dermatol Oct; 67(4):673.e1-10. Epub 2012 Jan 20. PMID: DOI: /j.jaad Shekunov J, Geske JR, Bostwick JM. Inpatient medical-surgical suicidal behavior: a 12-year case-control study. Gen Hosp Psychiatry Jul-Aug; 35(4): Epub 2013 Apr 15. PMID: DOI: /j.genhosppsych DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

13 Samuel C. Johnson Genomics of Addiction Program INVESTIGATORS Joanna M. Biernacka, Ph.D., Doo-Sup Choi, Ph.D., Mark A. Frye, M.D., Daniel K. Hall- Flavin, M.D., Victor M. Karpyak, M.D., Ph.D., Paul E. Croarkin, D.O., Keith D. Robertson, Ph.D., Terry D. Schneekloth, M.D., Marin Vedic, M.D., and Richard Weinshilboum, M.D. CLINICAL DISORDERS Back row, from left to right: Schneekloth, Karpyak, Hall-Flavin, Bobo Front row: Choi, Frye The Samuel C. Johnson Genomics of Addiction Program was designed to bring a multidisciplinary, integrated group of clinicians and scientists together to work synergistically to better understand how genetic vulnerability is related to the onset and treatment of alcohol use disorders. In addition, this multidisciplinary research team has concentrated on developing individualized molecular strategies for alcoholism treatment, with the primary focus on studying the pharmacogenomics of anti-craving medications. The S.C. Johnson research team was awarded a P20 developmental center grant from the National Institute on Alcohol Abuse and Alcoholism to establish the Center for Individualized Treatment of Alcohol Dependence (CITA). The primary goal of the funded research was to develop infrastructure for an expanding research team dedicated to designing and launching systematic pharmacogenomic and imaging studies of pharmacological treatments for alcoholism, initially focused on the medication acamprosate, an FDA-approved medication for treating alcoholism. The grant has funded the creation of an expanded multidisciplinary team of investigators who work together to design and conduct preclinical and clinical studies to identify which alcohol-dependent patients are most likely to benefit from acamprosate. With the successful implementation of the National Institutes of Health-supported P20 Center, Mayo S.C. Johnson investigators have published more than 110 peer-reviewed articles in major journals during the last three years in the field of addiction, neuroscience, genetics, and psychiatry. With future support from the NIH and benefactors this multidisciplinary research team plans to expand its studies to better understand the best individualized treatments for alcoholism

14 GRANTS National Institute of Alcohol Abuse and Alcoholism (R01): Alcohol and Adenosine-Mediated Glutamate Signaling in Neuro-Glial Interaction. Funding period: 09/ /2015; PI: Choi. National Institute of Alcohol Abuse and Alcoholism (R01): Developmental pathways, environmental agents, and epigenetics in liver disease. Funding period: 09/ /2016; PI K Robertson. S. C. Johnson Genomics of Addiction: Biomarker Development for Individualized Treatment of Alcoholism. Funding period: 01// /2017; PI: Choi. Department of Psychiatry and Psychology Research Grant: Orexin Signaling Mediates Ethanol Drinking Behavior in the Lateral Hypothalamic Kindled Female Rat Mania Model, the Impact of Pregnancy. Funding period: 04/ /2016; PI: Choi. Mayo-KI Collaborative Grant: Glutamate NMDA Receptor Signaling in Schizophrenia Disorders. Funding period: 03/ /2014; PI: Choi. Mayo-KI Collaborative Grant: Mathematical Neuroendocrine Modeling of the Lateral Hypothalamic Kindled Rat. Funding period: 03/01/ /01/2014; PI: Abulseoud. Co-I: Choi Mayo Clinic Center for Individualized Medicine Award: Epigenetic DNA Methylation in Bipolar Disorders. Funding period: 08/ /2015; PI: Veldic. Department of Psychiatry and Psychology Research Grant: Epigenetic Regulation of the Expression of Metabotropic Glutamate Receptors (mglur2 and mglur3) in Patients with Bipolar Disorder and without Comorbid Alcohol Use Disorder. Funding period: 01/ /2014; PI: Veldic, Co-PI: Blacker Marriott Foundation: Bipolar Biobank Biomarker Development (3BD) Program. Funding period: 01/13 12/17; PI: Frye, Co-PI: Biernacka, Co-I: Choi National Institute of Mental Health (K23): Glutamate Probes in Adolescent Depression. Funding period: 02/14 01/18; PI: Croarkin Brain and Behavior Research Foundation: Glutamate Neurotransmission in Depressed Adolescents at Risk for Bipolar Disorder. Funding period: 07/14 06/16; PI: Croarkin Mayo Clinic Center for Individualized Medicine Award: Genetic variation in the glycine signaling and metabolic pathways as a pharmacogenetic predictor of treatment response to acamprosate. 04/ /2013; PI: Karpyak KEY PUBLICATIONS Abulseoud OA, Camsari UM, Mohamed K, Abdel Gawd N, Ruby CL, Kasasbeh A, Yuksel MY, Choi DS. Lateral hypothalamic kindling induces manic-like behaviors in rats. Intl. J. Bipolar Dis. In Press, Abulseoud OA, Camsari UM, Ruby CL, Kasasbeh A, Choi S, Choi DS. Attenuation of ethanol withdrawal by ceftriaxoneinduced upregulation of glutamate transporter EAAT2. Neuropsychopharmacol. 39: , Bobo WV, Pathak J, Kremers HM, Yawn BP, Brue SM, Stoppel CJ, Croarkin PE, St Sauver J, Frye MA, Rocca WA. An electronic health record driven algorithm to identify incident antidepressant medication users. J. Am. Med. Inform Assoc. In Press, Chopra A, Abulseoud OA, Sampson S, Lee KH, Klassen BT, Fields JA, Matsumoto JY, Adams AC, Stoppel CJ, Geske JR, Frye MA. Mood Stability in Parkinson Disease Following Deep Brain Stimulation: A 6-Month Prospective Follow-up Study. Psychosomatics. In Press, Croarkin P, Thomas MA, Port JD, Baruth J, Choi DS, Abulseoud, OA, Frye MA. N-acetylaspartate normalization in bipolar depression after lamotrigine treatment. Bipolar Dis. In Press, Cuellar-Barboza AB, Frye, MA. Grothe K, Prieto ML, Schneekloth TD, Loukianova LL, Hall-Flavin DK, Clark MM, Karpyak VM, Miller JD, Abulseoud OA. Change in consumption patterns for treatmentseeking patients with alcohol use disorder post bariatric surgery. J Psychosom Res 2014 in press. Frye MA, Prieto ML, Bobo WV, Kung S, Veldic M, Alarcon RD, Moore KM, Choi DS, Biernacka JM, Tye SJ. Current landscape and unmet needs for treatment of bipolar depression (Review). J. Affect Dis. In Press, Grothe KB1, Mundi MS, Himes SM, Sarr MG, Clark MM, Geske JR, Kalsy SA, Frye MA. Bipolar Disorder Symptoms in Patients Seeking Bariatric Surgery. Obes Surg. In Press, Hinton DJ, Lee MR, Jang JS, Choi DS. ENT1 regulates glial fibrillary acidic protein expression in the striatum. Brain and Behavior. 4: , Hinton DJ, Lee MR, Kwong HK, Blanco MC, Choi DS. Aberrant bone density in the spine of aged mice lacking adenosine transporter ENT1. PLoS One. 9:288818, Hlady RH, Tiedemann RL, Puszyk W, Zendejas I, Roberts RL, Choi J-H, Liu C, Robertson KD. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis. Oncotarget. 5: , DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

15 Ji Y, Schaid DJ, Desta Z, Kubo M, Batzler AJ, Snyder K, Mushiroda T, Kamatani N, Ogbyrn E, Hall-Flavin D, Flockhart D, Nakamura T, Mrazek DA, Weinshilboum RM. Citalopram and escitalopram drug and metabolite concentrations: genome-wide associations. Br J Clin Pharmacol Aug; 78(2): PMCID: PMCID: DOI: /bcp Karpyak VM, Biernacka J, Geske JR, Jenkins D, Cunningham JM, Ruegg J, Kononenko O, Leontovich AA, Abulseoud O, Hall-Flavin D, Loukianova LL, Schneekloth TD, Skime M, Frank J, Nothen MM, Rietschel M, Kiefer F, Mann K, Weinshilboum RM, Frye MA, Choi DS. Genetic markers associated with abstinence length in alcohol dependent subjects treated with acamprosate. Translational Psychiatry. 4:e462, Karpyak VM, Romanowicz M, Schmidt JE, Lewis KA, Bostwick JM. Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users. Alcohol Clin. Exp. Res. 38:9-26, Karpyak VM, Winham SJ, Biernacka JM, Cunningham JM, Lewis KA, Geske JR, Colby CL, Abulseoud OA, Hall-Flavin DK, Loukianova LL, Schneekloth TD, Frye MA, Heit JA, Mrazek DA. Association of GATA4 sequence variation with alcohol dependence. Addict Biol. 19:312-5, Kolla BP, Schneekloth T, Biernacka J, Mansukhani M, Geske J, Karpyak V, Hall-Flavin D, Loukianova L, Frye MA. The course of sleep disturbances in early alcohol recovery: an observational cohort study. Am. J. Addict. 23:21-6, Lindberg D, Shan D, Ayers-Ringler J, Oliveros A, Benitez J, Prieto Cancino M, McCullumsmith R, Choi DS. Purinergic signaling and energy homeostasis in mental illness. Curr. Mol. Med. In Press, Mrazek DA, Biernacka JM, McAlpine DE, Benitez J, Karpyak VM, Williams MD, Hall-Flavin DK, Netzel PJ, Passov V, Rohland BM, Shinozaki G, Hoberg AA, Snyder KA, Drews MS, Skime MK, Sagen JA, Schaid DJ, Weinshilboum RM, Katzelnick DJ. Treatment Outcomes of Depression: The Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study. J Clin Psychopharmacol. In Press, Pathak J, Simon G, Li D, Biernacka JM, Jenkins G, Chute C, Hall- Flavin D, Weinshilboum R. Detecting associations between major depressive disorder treatment, essential hypertension using electronic health records. Accepted for publication Post RM, Altshuler LL, Leverich GS, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Nolen WA, Kupka RW, Grunze H, Rowe M. More medical comorbidities in patients with bipolar disorder from the United States than from the Netherlands and Germany. J. Nerv. Ment. Dis. 202:265-70, Prieto ML, Cuéllar-Barboza AB, Bobo WV, Roger VL, Bellivier F, Leboyer M, West CP, Frye MA. Risk of myocardial infarction and stroke in bipolar disorder: a systematic review and exploratory metaanalysis. Acta Psychiatr. Scand. In Press, Ruby CL, Vadnie CA, Hinton, DJ, Abulseoud OA, Walker DL, O Connor K, Noterman, MF, Choi DS. Adenosinergic Regulation of Striatal Clock Gene Expression and Ethanol Intake During Constant Light. Neuropsychopharmacol. 39: , Stamm TJ, Lewitzka U, Sauer C, Pilhatsch M, Smolka MN, Koeberle U, Adli M, Ricken R, Scherk H, Frye MA, Juckel G, Assion HJ, Gitlin M, Whybrow PC, Bauer M. Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study. J. Clin. Psychiatry. 75:162-8, Vadnie C, Hinton D, Choi S, Choi Y, Ruby C, Oliveros A, Prieto M, Park JH, Choi DS. Activation of neurotensin receptor type 1 attenuates locomotor activity. Neuropharmacol. 85: , Vadnie C, Park JH, Abdel-Gawad N, Ho ADC, Hinton, DA, Choi DS. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders (Review). Frontiers Neurosci. 8:288:1-25, Watanabe H, Fitting S, Hussain MZ, Kononenko O, Iatsyshyna A, Yoshitake T, Kehr J, Alkass K, Druid H, Wadensten H, Andren PE, Nylander I, Wedell DH, Krishtal O, Hauser KF, Nyberg F, Karpyak VM, Yakovleva T, Bakalkin G. Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate: a Putative Molecular Basis for Lateralization of Emotions and Pain. Cereb Cortex. In Press, Winham SJ, Barboza AC, McElroy S, Oliveros A, Crow S, Colin LC, Choi DS, Chauhan M, Frye M, Biernacka JM. Bipolar disorders with comorbid binge eating history: A genome-wide association study implicates APO. J. Affective Disorders. 165: , Winham SJ, Barboza AC, Oliveros A, McElroy S, Crow S, Colby C, Choi DS, Chauhan M, Frye M, Biernacka JM. Genome-wide association study of bipolar disorders accounting for effect of body mass index identifies a new risk allele in TCF7L2. Mol. Psychiatry. 19: , CLINICAL DISORDERS Post RM, Altshuler L, Kupka R, McElroy S, Frye MA, Rowe M, Leverich GS, Grunze H, Suppes T, Keck PE Jr, Nolen WA. More pernicious course of bipolar disorder in the United States than in many European countries: implications for policy and treatment. J. Affect. Disord. 160:27-33,

16 Individualized Medicine Biobank for Bipolar Disorder INVESTIGATORS Mark A. Frye, M.D., Joanna M. Biernacka, Ph.D, Christine W. Galardy, M.D., Ph.D., Simon Kung, M.D., Teresa A. Rummans, M.D., Bruce Sutor, M.D., Marin Veldic, M.D., Paul E. Croarkin, D.O., William V. Bobo, M.D., Susannah J. Tye, Ph.D., Doo-Sup Choi, Ph.D., Stacey J. Winham, Ph.D., (Rochester, Minnesota) and Elliott Richelson, M.D. (Jacksonville, Florida) Back row, left to right: Biernacka, Bobo, Frye, Choi, Winham Front row, left to right: Nassan, Veldic, Seymour Researchers in this team are establishing a large-scale biobank for bipolar type I disorder, collecting both biological samples and clinical data from 2,000 individuals. This is a multisite endeavor, with Mayo Clinic in Rochester, Minnesota, serving as the primary project site. Other sites that will assist in the recruitment of participants include Mayo Clinic in Jacksonville, Florida, Mayo Clinic in Scottsdale, Arizona, Austin Medical Center Mayo Health System (Austin, Minnesota), the Lindner Center of HOPE (Mason, Ohio), and the University of Minnesota. By establishing the infrastructure of this data-rich biobank, researchers hope to facilitate studies on disease risk and pharmacogenomic probes using state-of-the-art research technology. The identification of genetic risk factors associated with disease onset can potentially lead to early interventional treatment in at-risk patients. This early intervention is particularly important in bipolar disorder because the initiation of any treatment for bipolar disorder is often delayed by more than a decade from the time of onset. Additionally, identification of pharmacogenomic predictors of treatment response could provide increased selectivity to treatment recommendations, as well as help prevent such serious adverse events as antidepressant-induced mania DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

17 GRANT Mayo Clinic with a Generous Gift from the Marriott Family Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder Frye/Biernacka (Co-PIs) 12/ /2012 KEY PUBLICATIONS Croarkin PE, Thomas MA, Port JD, Baruth J, Choi D-S, Abulseoud OA, Frye MA. N-acetylaspartate normalization in bipolar depression after lamotrigine treatment. Bipolar Disord 2014 in press. Frye MA, McElroy SL, Prieto ML, Harper KL, Kung S, Chauhan M, Crow S, Sutor B, Galardy CW, Veldic M, Palmer BA, Geske JR, Fuentes M, Cuellar-Barboza AB, Seymour LR, Mori N, Biernacka JM. Clinical risk factors and serotonin transporter gene variants associated with antidepressant-induced mania. J Clin Psychiatry 2014 in press. Grothe KB, Mundi MS, Himes SM, Sarr MG, Clark MM, Geske JR, Kalsy SA, Frye MA. Bipolar disorder symptoms in patients seeking bariatric surgery. Obes Surg 2014 in press. Prieto ML, Cuellar Barboza AB, Bobo WV, Roger VL, Bellievier F, Leboyer M, West CP, Frye MA. Systematic review and metaanalysis of myocardial infarction and stroke risk in bipolar disorder: Implications for clinical practice and prevention. Acta Psychiatr Scand 2014 in press. Winham SJ, Cuellar-Barboza AB, McElroy SL, Oliveros A, Crow S, Colby CL, Choi D-S, Chauhan M, Frye MA, Biernacka JM. Bipolar disorder with comorbid binge eating history: A genome-wide association study implicates ApoB. J Affect Disord 2014 Aug; 165: Doi: /j.jad Epub 2014 Apr 19. ACADEMIC CAREER DEVELOPMENT Mark A. Frye, M.D. Scientific Reviewer. Member, NIMH Interventions Committee for Adult Disorders (ITVA) 2013 Present. PROFESSIONAL INTERNATIONAL PRESENTATIONS World Psychiatric Association s XVI World Congress of Psychiatry September 14-18, 2014, Madrid Spain Symposium Chair: Cardiovascular Disease and Obesity in Bipolar Disorder: Translational Research Focused on Epidemiology and Genetics, Mayo Clinic Bipolar Biobank: Focus on Metabolic Disorders. International Society of Bipolar Disorder August 22, 2014, Medellin, Colombia Plenary Session. Bipolar Disorder: Think Global Treat Local NOVEL METHODS FOR UNDERSTANDING Prieto ML, Youngstrom EA, Ozerdem A, Altinbas K, Quiroz D, Aydemir O, Yalin N, Geske JR, Feeder S, Angst J, and Frye MA. Different Patterns of Manic / Hypomanic Symptoms in Depression: a Pilot Modification of the Hypomania Checklist 32 to Assess Mixed Depression. J Affective Disorders 2014, in press

18 Psychiatric Pharmacogenomics And Pharmacometabolomics of Antidepressant Therapy INVESTIGATORS Richard Weinshilboum, M.D., Liewei Wang, M.D., Ph.D., Kurt B. Angstman, M.D., Joanna M. Biernacka, Ph.D., Meenal Gupta, Ph.D., Daniel K. Hall-Flavin, M.D., Astrid A. Hoberg, R.N., C.N.S., Yuan Ji, Ph.D., David J. Katzelnick, M.D., Balmiki Ray, MBBS, Barbara M. Rohland, M.D., Daniel J. Schaid, Ph.D., Karla A. Schroder, R.N., C.N.S., and Jeffrey P. Staab, M.D. Back row, left to right: Chai, Skime, Ray, Hofschulte Front row: Weinshilboum, Wang The primary objective of this research program is to better understand genetic variability as it relates to antidepressant response. This program has been supported since 2005 by a grant from the National Institute of General Medical Sciences (NIGMS) as part of the NIH Pharmacogenomics Research Network (PGRN), and over 800 Mayo patients with major depressive disorder (MDD) treated with citalopram or escitalopram have been studied. A second arm of this study involved the use of a serotoninnorepinephrine reuptake inhibitor, duloxetine, in patients who did not respond when treated with escitalopram or citalopram. In addition, this program also organized an International SSRI Pharmacogenomics Consortium (ISPC) that included samples from approximately 1000 SSRI-treated MDD patients. In 2010, the RIKEN Institute in Japan conducted a genome-wide association study (GWAS) of an initial PGRN patient cohort of 521 patients, and during the past year, RIKEN also performed a GWAS for the ISPC samples. Left to right: Karpyak, Bobo, Frye A new area of research that our team has recently undertaken involves the use of induced pluripotent stem (ips) cells. Under the leadership of Dr. Yuan Ji, the PGRN team received funding from the University of Minnesota Mayo Clinic partnership to study ips cell-derived neurons from MDD patients treated with SSRIs. Our team partnered with Timothy J. Nelson, MD, PhD, at Mayo Clinic, with colleagues at the University of Minnesota and with the Salk Institute for Biological Studies in California to study ips cell-derived neurons from a subset of patients who had participated in the PGRN SSRI study. Finally, a pharmacometabolomic study of escitalopram and citalopram response in the PGRN MDD patients has been completed that has identified novel biomarkers that provide insight into both variation in antidepressant therapy response and the pathophysiology of MDD DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY

19 GRANTS National Institute of General Medical Sciences (U19): Pharmacogenetics of Phase 2 Drug Metabolizing Enzymes Pharmacogenomic Clinical Study Core. Funding period: 07/ /2015; PI: Weinshilboum. Pharmacokinetics and Pharmacodynamics of SSRIs. National Institute of General Medical Sciences (R01): Inherited Variations in Drug Metabolizing Enzymes. Funding period: 06/01/12 3/31/16; PI: Weinshilboum. Minnesota Partnership for Biotechnology and Medical Genomics. Funding Period 1/01/211-1/31/2015; PIs: Ji and Weinshilboum. KEY PUBLICATIONS Abo, R., Hebbring, S., Ji, Y., Zhu, H., Zeng, Z.B., Batzler, A., Jenkins, G.D., Biernacka, J., Snyder, K., Drews, M., Fiehn, O., Fridley, B., Schaid, D., Kamatani, N., Nakamura, Y., Kubo, M., Mushiroda, T., Kaddurah-Daouk, R., Mrazek, D.A. and Weinshilboum, R.M.: Merging pharmacometabolomics with pharmacogenomics using 1000 Genomes SNP imputation: selective serotonin reuptake inhibitor response pharmacogenomics. Pharmacogenet Genomics 22(4): , PMID: ; PMCID: PMC Ellsworth, K., Moon, I., Eckloff, B.W., Fridley, B.L., Jenkins, G.D., Batzler, A., Biernacka, J., Abo, R., Brisbin, A., Ji, Y., Hebbring, S., Wieben, E.D., Mrazek, D.A., Weinshilboum, R.M. and Wang, L. FKBP5 genetic variation: association with SSRI treatment outcomes in major depressive disorder. Pharmacogenet Genomics Mar;23(3): doi: /FPC.0b013e32835dc133. PubMed PMID: ; PMCID: PMC Ji, Y., Schaid, D.J., Desta, Z., Kubo, M., Batzler, A., Snyder, K., Mushiroda, T., Kamatani, N., Ogburn, E., Hall-Flavin, D., Flockhart, D., Nakamura, Y., Mrazek, D. and Weinshilboum, R.M. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations. Br J Clin Pharmacol Aug;78(2): doi: /bcp PubMed PMID: ; PubMed Central PMCID: PMC Ji, Y., Biernacka, J.M., Hebbring, S., Chai, Y., Jenkins, G.D., Batzler, A., Snyder, K.A., Drews, M.S., Desta, Z., Flockhart, D., Mushiroda, T., Kubo, M., Nakamura, Y., Kamatani, N., Schaid, D., Weinshilboum, R.M. and Mrazek, D.A.: Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics. Pharmacogenomics J Aug (5): doi: /tpj [Epub ahead of print] PubMed PMID: ; PMCID: PMC Ji, Y., Biernacka, J., Snyder, K., Drews, M., Pelleymounter, L.L., Colby, C., Wang, L., Mrazek, D.A. and Weinshilboum, R.M.: Catechol O-methyltransferase pharmacogenomics and selective serotonin reuptake inhibitor response. The Pharmacogenomics J. 12:78-85, 2012 [Epub ahead of print 2010 Sep 28.]. PMID: ; PMCID: PMC Mrazek, D., Biernacka, J.M., McAlpine, D.E., Benitez, J., Karpyak, V.M., Williams, M.D., Hall-Flavin, D.K., Netzel, P.J., Passov, V., Rohland, B.M., Shinozaki, G., Hoberg, A.A., Snyder, K.A., Drews, M.S., Skime, M.K., Sagen, J.A., Schaid, D.J., Weinshilboum, R. and Katzelnick, D.J. Treatment outcomes of depression: the pharmacogenomic research network antidepressant medication pharmacogenomic study. J Clin Psychopharmacol Jun;34(3): PubMed PMID: ; PubMed Central PMCID: PMC NOVEL METHODS FOR UNDERSTANDING

20 Translational Neuroscience Laboratory INVESTIGATORS Susannah J. Tye, Ph.D., Doo-Sup Choi, Ph.D., Joanna M. Biernacka Ph.D., Victor M. Karpyak, M.D., Ph.D., Marin Veldic, M.D., Paul E. Croarkin, D.O., Shari L. Sutor MA, and Mark A. Frye, M.D. Back row, from left to right: Choi, Tye, Croarkin, Sutor, Frye, Veldic Front row: Abulseoud, Karpyak, Biernacka Our Translational Neuroscience Laboratory provides the space and expertise for members of the Department of Psychiatry & Psychology to conduct cutting-edge research in translational neuroscience, genomic psychiatry, and biomarker discovery using the latest cellular, molecular, and genetic technologies. Biomarker discovery has already had an immense impact upon the prevention and treatment of many diseases, but remains in its relative infancy in psychiatry. Our research combines multiple scientific approaches to bring new insight into the causes of psychiatric illness and factors mediating individual treatment outcomes. Our bench to bedside and back to bench framework is helping us to better understand the interplay between genetic and environmental risk factors so that we can provide more targeted treatments for patients. Recent research projects have focused on defining the role of genetic and environmental factors in depression, bipolar disorder, and alcoholism. In combination with our focused search for biomarkers of treatment response, the outcomes of this research will enable us to individualize patient care and tailor treatments in ways not previously possible. In addition to this, our facility functions as a classroom for trainees and faculty in psychiatry and psychology who are interested in learning how to do preclinical and bench-top research. Several of these individuals have gone on to develop their own research careers in of psychiatric genetics, epigenetics, biomarker development and preclinical modeling. GRANTS Brain and Behavior Research Foundation, NARSAD Young Investigator Award. Glutamatergic Neurotransmission in Youth at Risk for Bipolar Disorder. (PI: Croarkin, Mentor: Frye) 07/ /2015. MINH Mentored Patient-Orientated Research Career Development Award 1K23MH A1, Glutamate Probes in Adolescent Depression. (PI: Croarkin, Mentor: Frye) 02/ / DEPARTMENT OF PSYCHIATRY AND PSYCHOLOGY