Besterman, Aaron D.

Moreno-De-Luca, Daniel

Nurnberger, John I., Jr.

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21st-Century Genetics in Psychiatric Residency Training: How Do We Get There?

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Besterman, Aaron D

Nurnberger, John I

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UC San DiegoUC San Diego Previously Published WorksTitle21st-Century Genetics in Psychiatric Residency TrainingPermalinkhttps://escholarship.org/uc/item/4hz4x56cJournalJAMA Psychiatry, 76(3)ISSN2168-622XAuthorsBesterman, Aaron DMoreno-De-Luca, DanielNurnberger, John IPublication Date2019-03-01DOI10.1001/jamapsychiatry.2018.3872Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of California21st-Century Genetics in Psychiatric Residency Training:How Do We Get There?Aaron D. Besterman, MD,Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles; and Division of Child and Adolescent Psychiatry, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles.Daniel Moreno-De-Luca, MD, MSc,Division of Child and Adolescent Psychiatry, Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Riverside, Rhode Island.John I. Nurnberger Jr, MD, PhDDepartments of Psychiatry, Medical, and Molecular Genetics, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis.Our expanding knowledge of how variation in the human genome contributes to complex diseases has propelled many recent advances in medicine. In oncology, understanding the genetic basis of cancer predisposition, tumor growth, and treatment response has become an essential part of the field and its training. Although current diagnoses in psychiatry are based on clinical observations, we are approaching a time when our genetic and molecular understanding of mental illness may play an important role in etiological understanding and treatment.1It is now well established that different types of genetic variations can increase one’s risk for psychiatric disorders. For example, highly penetrant rare variants in hundreds of genes or genomic regions have been strongly associated with autism spectrum disorders (ASD), intellectual disability, and developmental delay, while common variants in more than 100 locations in the human genome have been statistically linked to schizophrenia.1 The translation of these research findings is starting to permeate psychiatric clinical practice in particular areas. Genetic testing, specifically chromosomal microarray and Fragile X testing, is now recommended for all patients with ASD, intellectual disabilities, and developmental delay.1 Highly penetrant rare variants are found on chromosomal microarray in 10% to 30% of individuals with these disorders and can have implications on clinical management (Table).1 Despite these recommendations, genetic testing is occurring only for a minority of these patients. Conversely, pharmacogenetic testing, which can provide information about a patient’s drug metabolism rates, response, and risk for adverse events, is widely available Corresponding Author: John I. Nurnberger, MD, PhD, Indiana University School of Medicine, 320 W 15th St, Ste 200E, Indianapolis, IN 46202-2266 (jnurnber@iupui.edu). jamapsychiatry.com. Conflict of Interest Disclosures: Dr Nurnberger has served as an investigator for Assurex and is currently an investigator for Janssen. No other disclosures are reported.HHS Public AccessAuthor manuscriptJAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Published in final edited form as:JAMA Psychiatry. 2019 March 01; 76(3): 231–232. doi:10.1001/jamapsychiatry.2018.3872.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscriptthrough direct-to-consumer tests and frequently used despite a significant need for additional research demonstrating improved clinical outcomes for psychiatric patients.2As a field, we must be able to confidently assess and critically appraise the evidence supporting these and other genetic tests. We must understand the concepts that drive these recommendations to properly use this information to enhance patient care. However, current education about genetics across psychiatry residencies and fellowships is heterogeneous and sparse.3 Psychiatry residents generally leave training programs with low levels of genetics literacy, which may lead to an apprehension about using genetic tools and integrating genetic principles into clinical care.4 This “education gap” will only widen as the understanding of psychiatric genetics and our ability to translate this knowledge into the clinic expands. Efforts by organizations, such as the American College of Graduate Medical Education and the American Board of Psychiatry and Neurology, to increase their emphasis on the emerging role of genetics in psychiatry will be important to bring attention to this issue. Closing this gap will also require modernized and standardized residency and fellowship education curricula for psychiatric genetics. Efforts to address these issues are currently underway.The International Society of Psychiatric Genetics Committee on Resident Education (CRE) was created in 2015 with the goals of (1) identifying specific areas in genetics and genomics that are essential for all psychiatrists to understand and (2) collaborating with other organizations to create training material that builds on these defined key knowledge areas. Through a review of the relevant literature and consensus, the CRE has produced a full description of the learning objectives.5 Briefly, the objectives cover the basic principles of genetics, common genetic variants, rare genetic variants, pharmacogenetics, epigenetics/gene expression, ethical and social issues in genetics, and principles of risk communication. The CRE is currently working with partners to create educational modules that are based on these recommendations, with a focus on creating material that is free, universally available, frequently updated to reflect novel discoveries, based on principles of adult learning, clinically grounded, and potentially administered without depending on local expert faculty.6 However, further research is needed on the effectiveness of nonexperts teaching psychiatric genetics with these supportive tools.One of our partners is the National Neuroscience Curriculum Initiative,6 which creates freely available online learning activities on various neuroscience topics (http://www.nncionline.org) and uses many of the key education principles discussed previously. There are currently modules on genetic testing for rare variants in ASD and pharmacogenetic testing in bipolar disorder. The 2 modules serve different but important purposes. The ASD module encourages clinicians to order diagnostic testing and helps them understand and interpret results and their implications for clinical management. The pharmacogenetics module encourages residents to think critically about using testing given the limited evidence supporting its clinical benefits.Psychiatry is not the only medical specialty that is seeking to improve genetics education. The Inter-Society Coordinating Committee for Practitioner Education in Genomics was formed in 2013 by the National Human Genome Institute to “improve genomic literacy Besterman et al. Page 2JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscriptof physicians and other practitioners and to enhance the practice of genomic medicine through sharing of educational approaches and joint identification of educational needs.”7 It includes 56 current member organizations representing all fields of medicine (http://www.genome.gov/27554614) (including the International Society of Psychiatric Genetics). The Inter-Society Coordinating Committee for Practitioner Education in Genomics recently published “The Universal Genomics Instructor Handbook and Toolkit,” which is a new, free educational resource designed to educate clinicians in all medical specialties in genomic medicine (http://www.pathologylearning.org/trig/resources). The customizable nature of this tool allows many different clinicians with different levels of genetics knowledge to benefit from it. It can also be easily updated as our knowledge advances.Looking to the future, we must be prepared as a field to tackle the challenge of creating high-quality, interactive, and accessible training materials that communicate increasingly complicated concepts in genetics. For example, psychiatry residents will need to understand the concepts of polygenicity and pleiotropy and learn how multiple genetic risk factors may in the future be combined to predict disease or treatment outcomes (eg, polygenic risk score). They will need to learn to integrate genetic information with other biological, psychological, and social information to optimize clinical care for patients. We encourage psychiatry training programs to consider the increasing role that genetics and precision medicine are playing in our field and tailor curricula accordingly. Programs can make use of new, free, and publicly available materials regardless of levels of expertise among the faculty. With a greater understanding of psychiatric genetics, 21st century psychiatrists will feel empowered to use modern genetic tools to better serve patients.AcknowledgmentsAdditional Contributions: We thank all of the members of International Society of Psychiatric Genetics Taskforce on Residency Education for their thoughtful discussion and feedback. They were not compensated for their contributions.REFERENCES1. Vorstman JAS, Parr JR, Moreno-De-Luca D, Anney RJL, Nurnberger JI Jr, Hallmayer JF. Autism genetics: opportunities and challenges for clinical translation. Nat Rev Genet. 2017;18(6):362–376. doi: 10.1038/nrg.2017.4 [PubMed: 28260791] 2. Hirschtritt ME, Besterman AD, Ross DA. Psychiatric pharmacogenomics: how close are we?Biol Psychiatry. 2016;80(8):e63–e65. doi:10.1016/j.biopsych.2016.08.007 [PubMed: 27663067] 3. Hoop JG, Savla G, Roberts LW, Zisook S, Dunn LB. The current state of genetics training in psychiatric residency: views of 235 U.S. educators and trainees. Acad Psychiatry. 2010;34(2):109–114. doi:10.1176/appi.ap.34.2.109 [PubMed: 20224019] 4. Salm M, Abbate K, Appelbaum P, et al.Use of genetic tests among neurologists and psychiatrists: knowledge, attitudes, behaviors, and needs for training. J Genet Couns. 2014;23(2):156–163. doi:10.1007/s10897-013-9624-0 [PubMed: 23793969] 5. Nurnberger J, Austin JC, Berrettini W, et al.What should a psychiatrist know about genetics? review and recommendations from the Residency Education Committee of the International Society of Psychiatric Genetics. J Clin Psychiatry. In press.6. Arbuckle MR, Travis MJ, Ross DA. Integrating a neuroscience perspective into clinical psychiatry today. JAMA Psychiatry. 2017;74(4):313–314. doi:10.1001/jamapsychiatry.2016.3849 [PubMed: 28273288] Besterman et al. Page 3JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript7. Korf BR, Berry AB, Limson M, et al.Framework for development of physician competencies in genomic medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee for Physician Education in Genomics. Genet Med. 2014;16(11):804–809. doi:10.1038/gim.2014.35 [PubMed: 24763287] Besterman et al. Page 4JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptBesterman et al. Page 5Table.Clinical Benefits of Genetic Testing and Counseling in PsychiatryClinical BenefitExampleImplicationImproved etiologic understanding of the disorderA de novo deletion of 16p11.2 is identified in a patient with ASDParents understand that the etiology of their child’s condition is due to a new genetic change and not due to a deficiency in their parenting (https://rarediseases.info.nih.gov/diseases/10740/16p112-deletion­syndrome)Community support for the patient and familyA patient with developmental delay receives a diagnosis of 15q11-q13 duplication syndromeThe patient and family can find resources, advocacy opportunities, and other families affected by this syndrome through the Dup15q alliance (http://www.dup15q.org)Reproductive counseling and family planningThe parents of a patient with childhood-onset schizophrenia and a de novo 22q11.2 deletion are considering having a second childThe parents are counseled that the chance of having a second child with 22q11.2 deletion syndrome is slightly increased compared with the general population based on studies of siblings of patients with ASD1  (https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome)Ongoing surveillance for known comorbiditiesA patient with ASD receives a diagnosis of PTEN deletionThe patient has a known elevated risk of cancer. Ongoing cancer monitoring is provided to the patientExperimental treatment referralsA patient with ASD receives a diagnosis of 22q13 deletion syndromePossible referral to a clinical trial for IGF-1 therapy (https://www.mountsinai.org/clinical-trials/pilot­treatment-study-of-insulin-like-growth-factor-1igf-1-in-autism-spectrum-disorder)Reduce risk of severe medication adverse effectsA patient of Han Chinese ethnicity with bipolar disorder carries the HLA-B*15:02 variantThe patient would not be administered carbamazepine because of their significantly elevated risk of Stevens-Johnson syndrome2 (https://www.pharmgkb.org/guideline/PA166105008)Abbreviations: ASD, autism spectrum disorders; IGF-1, insulin-like growth factor1; PTEN, phosphatase and tensin homolog.JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.

English

21st-Century Genetics in Psychiatric Residency Training

21st-Century Genetics in Psychiatric Residency Training:How Do We Get There?Aaron D. Besterman, MD,Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles; and Division of Child and Adolescent Psychiatry, Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles.Daniel Moreno-De-Luca, MD, MSc,Division of Child and Adolescent Psychiatry, Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Riverside, Rhode Island.John I. Nurnberger Jr, MD, PhDDepartments of Psychiatry, Medical, and Molecular Genetics, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis.Our expanding knowledge of how variation in the human genome contributes to complex diseases has propelled many recent advances in medicine. In oncology, understanding the genetic basis of cancer predisposition, tumor growth, and treatment response has become an essential part of the field and its training. Although current diagnoses in psychiatry are based on clinical observations, we are approaching a time when our genetic and molecular understanding of mental illness may play an important role in etiological understanding and treatment.1It is now well established that different types of genetic variations can increase one’s risk for psychiatric disorders. For example, highly penetrant rare variants in hundreds of genes or genomic regions have been strongly associated with autism spectrum disorders (ASD), intellectual disability, and developmental delay, while common variants in more than 100 locations in the human genome have been statistically linked to schizophrenia.1 The translation of these research findings is starting to permeate psychiatric clinical practice in particular areas. Genetic testing, specifically chromosomal microarray and Fragile X testing, is now recommended for all patients with ASD, intellectual disabilities, and developmental delay.1 Highly penetrant rare variants are found on chromosomal microarray in 10% to 30% of individuals with these disorders and can have implications on clinical management (Table).1 Despite these recommendations, genetic testing is occurring only for a minority of these patients. Conversely, pharmacogenetic testing, which can provide information about a patient’s drug metabolism rates, response, and risk for adverse events, is widely available Corresponding Author: John I. Nurnberger, MD, PhD, Indiana University School of Medicine, 320 W 15th St, Ste 200E, Indianapolis, IN 46202-2266 (jnurnber@iupui.edu). jamapsychiatry.com. Conflict of Interest Disclosures: Dr Nurnberger has served as an investigator for Assurex and is currently an investigator for Janssen. No other disclosures are reported.HHS Public AccessAuthor manuscriptJAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Published in final edited form as:JAMA Psychiatry. 2019 March 01; 76(3): 231–232. doi:10.1001/jamapsychiatry.2018.3872.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscriptthrough direct-to-consumer tests and frequently used despite a significant need for additional research demonstrating improved clinical outcomes for psychiatric patients.2As a field, we must be able to confidently assess and critically appraise the evidence supporting these and other genetic tests. We must understand the concepts that drive these recommendations to properly use this information to enhance patient care. However, current education about genetics across psychiatry residencies and fellowships is heterogeneous and sparse.3 Psychiatry residents generally leave training programs with low levels of genetics literacy, which may lead to an apprehension about using genetic tools and integrating genetic principles into clinical care.4 This “education gap” will only widen as the understanding of psychiatric genetics and our ability to translate this knowledge into the clinic expands. Efforts by organizations, such as the American College of Graduate Medical Education and the American Board of Psychiatry and Neurology, to increase their emphasis on the emerging role of genetics in psychiatry will be important to bring attention to this issue. Closing this gap will also require modernized and standardized residency and fellowship education curricula for psychiatric genetics. Efforts to address these issues are currently underway.The International Society of Psychiatric Genetics Committee on Resident Education (CRE) was created in 2015 with the goals of (1) identifying specific areas in genetics and genomics that are essential for all psychiatrists to understand and (2) collaborating with other organizations to create training material that builds on these defined key knowledge areas. Through a review of the relevant literature and consensus, the CRE has produced a full description of the learning objectives.5 Briefly, the objectives cover the basic principles of genetics, common genetic variants, rare genetic variants, pharmacogenetics, epigenetics/gene expression, ethical and social issues in genetics, and principles of risk communication. The CRE is currently working with partners to create educational modules that are based on these recommendations, with a focus on creating material that is free, universally available, frequently updated to reflect novel discoveries, based on principles of adult learning, clinically grounded, and potentially administered without depending on local expert faculty.6 However, further research is needed on the effectiveness of nonexperts teaching psychiatric genetics with these supportive tools.One of our partners is the National Neuroscience Curriculum Initiative,6 which creates freely available online learning activities on various neuroscience topics (http://www.nncionline.org) and uses many of the key education principles discussed previously. There are currently modules on genetic testing for rare variants in ASD and pharmacogenetic testing in bipolar disorder. The 2 modules serve different but important purposes. The ASD module encourages clinicians to order diagnostic testing and helps them understand and interpret results and their implications for clinical management. The pharmacogenetics module encourages residents to think critically about using testing given the limited evidence supporting its clinical benefits.Psychiatry is not the only medical specialty that is seeking to improve genetics education. The Inter-Society Coordinating Committee for Practitioner Education in Genomics was formed in 2013 by the National Human Genome Institute to “improve genomic literacy Besterman et al. Page 2JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscriptof physicians and other practitioners and to enhance the practice of genomic medicine through sharing of educational approaches and joint identification of educational needs.”7 It includes 56 current member organizations representing all fields of medicine (http://www.genome.gov/27554614) (including the International Society of Psychiatric Genetics). The Inter-Society Coordinating Committee for Practitioner Education in Genomics recently published “The Universal Genomics Instructor Handbook and Toolkit,” which is a new, free educational resource designed to educate clinicians in all medical specialties in genomic medicine (http://www.pathologylearning.org/trig/resources). The customizable nature of this tool allows many different clinicians with different levels of genetics knowledge to benefit from it. It can also be easily updated as our knowledge advances.Looking to the future, we must be prepared as a field to tackle the challenge of creating high-quality, interactive, and accessible training materials that communicate increasingly complicated concepts in genetics. For example, psychiatry residents will need to understand the concepts of polygenicity and pleiotropy and learn how multiple genetic risk factors may in the future be combined to predict disease or treatment outcomes (eg, polygenic risk score). They will need to learn to integrate genetic information with other biological, psychological, and social information to optimize clinical care for patients. We encourage psychiatry training programs to consider the increasing role that genetics and precision medicine are playing in our field and tailor curricula accordingly. Programs can make use of new, free, and publicly available materials regardless of levels of expertise among the faculty. With a greater understanding of psychiatric genetics, 21st century psychiatrists will feel empowered to use modern genetic tools to better serve patients.AcknowledgmentsAdditional Contributions: We thank all of the members of International Society of Psychiatric Genetics Taskforce on Residency Education for their thoughtful discussion and feedback. They were not compensated for their contributions.REFERENCES1. Vorstman JAS, Parr JR, Moreno-De-Luca D, Anney RJL, Nurnberger JI Jr, Hallmayer JF. Autism genetics: opportunities and challenges for clinical translation. Nat Rev Genet. 2017;18(6):362–376. doi: 10.1038/nrg.2017.4 [PubMed: 28260791] 2. Hirschtritt ME, Besterman AD, Ross DA. Psychiatric pharmacogenomics: how close are we?Biol Psychiatry. 2016;80(8):e63–e65. doi:10.1016/j.biopsych.2016.08.007 [PubMed: 27663067] 3. Hoop JG, Savla G, Roberts LW, Zisook S, Dunn LB. The current state of genetics training in psychiatric residency: views of 235 U.S. educators and trainees. Acad Psychiatry. 2010;34(2):109–114. doi:10.1176/appi.ap.34.2.109 [PubMed: 20224019] 4. Salm M, Abbate K, Appelbaum P, et al.Use of genetic tests among neurologists and psychiatrists: knowledge, attitudes, behaviors, and needs for training. J Genet Couns. 2014;23(2):156–163. doi:10.1007/s10897-013-9624-0 [PubMed: 23793969] 5. Nurnberger J, Austin JC, Berrettini W, et al.What should a psychiatrist know about genetics? review and recommendations from the Residency Education Committee of the International Society of Psychiatric Genetics. J Clin Psychiatry. In press.6. Arbuckle MR, Travis MJ, Ross DA. Integrating a neuroscience perspective into clinical psychiatry today. JAMA Psychiatry. 2017;74(4):313–314. doi:10.1001/jamapsychiatry.2016.3849 [PubMed: 28273288] Besterman et al. Page 3JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript7. Korf BR, Berry AB, Limson M, et al.Framework for development of physician competencies in genomic medicine: report of the Competencies Working Group of the Inter-Society Coordinating Committee for Physician Education in Genomics. Genet Med. 2014;16(11):804–809. doi:10.1038/gim.2014.35 [PubMed: 24763287] Besterman et al. Page 4JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptBesterman et al. Page 5Table.Clinical Benefits of Genetic Testing and Counseling in PsychiatryClinical BenefitExampleImplicationImproved etiologic understanding of the disorderA de novo deletion of 16p11.2 is identified in a patient with ASDParents understand that the etiology of their child’s condition is due to a new genetic change and not due to a deficiency in their parenting (https://rarediseases.info.nih.gov/diseases/10740/16p112-deletion­syndrome)Community support for the patient and familyA patient with developmental delay receives a diagnosis of 15q11-q13 duplication syndromeThe patient and family can find resources, advocacy opportunities, and other families affected by this syndrome through the Dup15q alliance (http://www.dup15q.org)Reproductive counseling and family planningThe parents of a patient with childhood-onset schizophrenia and a de novo 22q11.2 deletion are considering having a second childThe parents are counseled that the chance of having a second child with 22q11.2 deletion syndrome is slightly increased compared with the general population based on studies of siblings of patients with ASD1  (https://ghr.nlm.nih.gov/condition/22q112-deletion-syndrome)Ongoing surveillance for known comorbiditiesA patient with ASD receives a diagnosis of PTEN deletionThe patient has a known elevated risk of cancer. Ongoing cancer monitoring is provided to the patientExperimental treatment referralsA patient with ASD receives a diagnosis of 22q13 deletion syndromePossible referral to a clinical trial for IGF-1 therapy (https://www.mountsinai.org/clinical-trials/pilot­treatment-study-of-insulin-like-growth-factor-1igf-1-in-autism-spectrum-disorder)Reduce risk of severe medication adverse effectsA patient of Han Chinese ethnicity with bipolar disorder carries the HLA-B*15:02 variantThe patient would not be administered carbamazepine because of their significantly elevated risk of Stevens-Johnson syndrome2 (https://www.pharmgkb.org/guideline/PA166105008)Abbreviations: ASD, autism spectrum disorders; IGF-1, insulin-like growth factor1; PTEN, phosphatase and tensin homolog.JAMA Psychiatry. Author manuscript; available in PMC 2021 August 30.

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21st-Century Genetics in Psychiatric Residency Training: How Do We Get There?

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