OBSESSIVE COMPULSIVE DISORDER CURRENT STATE OF THE RESEARCH FIELD & OPPORTUNITIES FOR PHILANTHROPY Rodan Family Foundation The Rodan Family Foundation aims to invest significantly in the OCD esearchr field with the goal of eliminating symptoms for those with treatment-resistant OCD, freeing them to lead fully functional, meaningful and happy lives.

Rockefeller Philanthropy Advisors Rockefeller Philanthropy Advisors (RPA) is a nonprofit organization that currently advises on and manages more than $200 million in annual giving by individuals, families, corporations, and major foundations. Continuing the Rockefeller family’s legacy of thoughtful, effective philanthropy, RPA remains at the forefront of philanthropic growth and innovation, with a diverse team led by experienced grantmakers with significant depth of knowledge across the spectrum of issue areas. Founded in 2002, RPA has grown into one of the world’s largest philanthropic service organizations and, as a whole, has facilitated more than $3 billion in grantmaking to nearly 70 countries. For more information, please visit www.rockpa.org.

© May 2019 TABLE OF CONTENTS

1 Introduction 2 Methodology 3 Executive Summary 3 Current State of the OCD Research Field 5 Philanthropic Opportunities 6 Part One: Current State of the OCD Field 6 Definition and Diagnosis 8 Treatment 8 Current Challenges in Access to Care 10 Slow Progress on Research 16 Part Two: Ecosystem of Research Stakeholders 16 Government 19 Philanthropy 23 Institutions 27 Researchers 28 Part Three: Emerging Research 28 Science 33 Treatment 40 Part Four: Moving the Field Forward 40 Short-Term 41 Medium-Term 41 Long-Term 43 Part Five: Recommendations for Philanthropy 43 Philanthropic Opportunities 45 Philanthropic Approaches 52 Measuring Progress 53 Conclusion 54 Endnotes Introduction & Methodology 1

learning agenda to inform its philanthropic strategy in the OCD field. learning agenda to inform its philanthropic The Rodan Family Foundation, a family foundation based outside of San Francisco, The Rodan Family Foundation, a family foundation based in OCD research, in advancements made California, and deeply interested as part of its Advisors (RPA) Philanthropy Rockefeller from commissioned the report OCD research as of July 2019, this is not an exhaustive report. OCD research with philanthropic resources available to support the field, this report will be useful report will be useful available to support the field, this resources with philanthropic and the latest developments the disorder for anyone seeking to better understand to relating While it aims to objectively cover all key areas and treatment. in research Written as a practical guide for those seeking more information on OCD and for those information on OCD and for as a practical guide for those seeking more Written list of leading OCD research centers, a description of emerging research, promising promising research, centers, a description of emerging list of leading OCD research initial considerations for and field forward, efforts focused on moving the investment opportunities. philanthropic that will move the field forward at a faster pace to effectively treat more people. This people. treat more at a faster pace to effectively that will move the field forward relevant stakeholders, a state of the field, includes an overview of the current report This report provides a snapshot of the current state of OCD research and the and the state of OCD research a snapshot of the current provides This report lens to identify opportunities using a philanthropic based on that research, treatments and advocacy. Due to a number of barriers, however, progress has been slow and progress Due to a number of barriers, however, and advocacy. of the disorder. the symptoms from many people continue to suffer treatments do not work. The field has been working for the past 30 years to address to address working for the past 30 years do not work. The field has been treatments development, awareness, treatment research, the needs of that population through that help some people reduce symptoms and lead functional lives; however, there are are there lives; however, symptoms and lead functional people reduce that help some diagnosed—for whom current of those of people—30 to 50 percent a good number obsessive compulsive disorder (OCD) in their lifetimes. While seemingly a small their lifetimes. While seemingly (OCD) in disorder obsessive compulsive of leaving millions and mis-diagnosed, under- the condition is vastly number, exist treatments Good, effective with unexplained symptoms. Americans suffering Approximately two percent of adults in the United States are diagnosed with diagnosed with in the United States are of adults two percent Approximately INTRODUCTION Introduction & Methodology 2 : RPA used resources from its own its from used resources : RPA : RPA conducted hour-long phone interviews with 21 experts phone interviews conducted hour-long : RPA

Leveraged existing institutional knowledge Leveraged existing institutional : RPA conducted a literature review of leading medical review conducted a literature : RPA review Conducted a literature relevant published research the most recently journals and publications to gather to OCD. solicited written descriptions : RPA leading centers of research information from Gathered as leaders in the field during centers that emerged ten OCD research the from was to better of the research and interviews. The purpose of this aspect research of the research histories and approaches backgrounds, understand the respective centers. Interviewed field experts Interviewed field 20 percent approximately This represents and funding. treatment, in OCD research, in the United States. field of the active research to a leading grantmaker in the OCD field. advisor experience as the philanthropy ƒ ƒ ƒ RPA analyzed the findings and synthesized them into the key themes presented in them into the key themes presented analyzed the findings and synthesized RPA an overview of stakeholders; state of the field; which includes the current this report, opportunities. and future research; challenges to the field; emerging ƒ To uncover information about the above, RPA: uncover information about To Research and analysis for this report focused on: i) the current state of OCD treatment state of OCD treatment current focused on: i) the for this report and analysis Research the and iii) and research; funding landscape for OCD treatment ii) the and research people effectively. more in treating to move the field forward best opportunities METHODOLOGY Executive Summary 3 . ogress of research research of ogress : The U.S. National Institute of Mental Health (NIMH) funded $27 : The U.S. National Institute of Mental Health (NIMH) funded

million in 2018 (as of September 2018) for 72 OCD research projects. million in 2018 (as of September 2018) for 72 OCD research Government million in $3.5 : The International OCD Foundation has provided Philanthropy Foundation has funding since 1994; the Brain & Behavior Research OCD research funding since 1987; and private families and $4 million to OCD research provided funding. individuals have also provided Sluggish research progress due to the complexity of the disorder, poor due to the complexity of the disorder, progress Sluggish research understanding of the disorder’s lack of biological origins, small sample sizes, entering the field, and lack of collaboration. funding, weak pipeline of researchers Low awareness and high stigma of the disorder. Low awareness Lack of effective treatments. Limited access to providers. ƒ There are three major players in the OCD ecosystem. three are There ƒ ECOSYSTEM OF RESEARCH STAKEHOLDERS ECOSYSTEM ƒ and prevented more people with OCD from receiving effective treatment. Leading effective treatment. receiving people with OCD from more and prevented challenges include: ƒ ƒ ƒ The OCD field faces a number of challenges that have slowed the pr The OCD field faces a number CURRENT CHALLENGES Approximately two percent of adults in the United States are diagnosed with diagnosed with in the United States are of adults two percent Approximately this number their lifetimes. However, (OCD) in disorder obsessive compulsive among given the recognition full extent of the disorder the doesn’t represent for OCD include treatments and mis-diagnosed. First-line under- experts that it is therapy (ERP) in prevention response (CBT)—exposure cognitive behavioral therapy were treatments These (SSRIs). inhibitors reuptake serotonin selective particular—and of those diagnosed only 50 to 70 percent treat developed 30 years ago and effectively brain include other antipsychotic medications, with OCD. Second-line treatments methods for delivering psychotherapy stimulation therapies, and alternative CURRENT STATE OF THE OCD RESEARCH FIELD OCD RESEARCH OF THE STATE CURRENT EXECUTIVE SUMMARY EXECUTIVE Executive Summary 4 , University of Pennsylvania University of Pittsburgh University Yale University of California Los Angeles Semel Institute of Neuroscience University of California Los and Human Behavior University of California San Francisco University of Florida Massachusetts General Hospital/Harvard Medical School General Hospital/Harvard Massachusetts Corporation The McLean Hospital Rogers Behavioral Health University Stanford Brown University—Butler Hospital and Bradley Hospital Hospital and Bradley University—Butler Brown Columbia University Medical Institutions Johns Hopkins Baylor College of Medicine Baylor College y y y y y y y y y y y y y y y y y y y y y y y y y y y y : Find better ways to diagnose and treat people. : Find better ways to diagnose and treat Medium-term approach basic science through : Understand the causes of the disorder Long-term approach level functioning a deeper understanding of the neurocircuit that develops research and the suite of genes implicated. : Better disseminate existing treatments and increase access to access and increase : Better disseminate existing treatments Short-term approach care. : Several institutions conduct OCD research. Those OCD research. institutions conduct : Several institutions treatment and Research report. for this the research included in were noted below ƒ ƒ ƒ MOST PROMISING AVENUES FOR MOVING THE FIELD FORWARD FOR MOVING PROMISING AVENUES MOST ways to influence the the following as the most promising Experts recommend lives. people to live symptom-free to enable more trajectory of OCD research The field is making advances in discoveries related to neural circuits, neurotransmitters, neurotransmitters, related to neural circuits, in discoveries The field is making advances development targeting advances include drug Treatment genetics, and immunology. methods of psychotherapy (e.g., intensive CBT glutamate modulation, alternative bias inhibitory learning, attention therapy, acceptance & commitment family therapy, non-invasive and invasive of methods new and technology), of use the and modification, deep brain stimulation). brain stimulation (e.g., transcranial magnetic stimulation and EMERGING RESEARCH ƒ Executive Summary 5 connect stakeholders across the field (researchers, clinicians, advocates, (researchers, the field across connect stakeholders provide sustained research funding to: alleviate the pressure of chasing the pressure funding to: alleviate sustained research provide High-risk, high reward grantmaking with a focus on funding innovation. High-risk, high reward Multi-pronged grantmaking that focuses on short-, medium-, and long-term Multi-pronged outcomes. using the power of competition to achieve significant The “prize” approach, advances in therapeutics. Donor collaboratives. university-based approach. scale, multi-disciplinary, “Big bets,” utilizing a large Supporting advocacy and awareness. Funding basic research, translational research, and treatment development. and treatment research, translational Funding basic research, and psychologists. Funding training for psychiatrists dissemination. Funding treatment attract additional funding from government and other sources, fund government and other sources, Catalysts attract additional funding from grants, and enhance government that could lead to larger innovative research government which could further increase advocacy and awareness, efforts around spending allocations for OCD. Sustainers collaboration; and promote ambitious projects; allow more grant funding; field. to enter the researchers encourage new Connectors ambitious goals. common, funders) toward ƒ ƒ ƒ ƒ ƒ These strategies to move the OCD field forward can be implemented through various through can be implemented These strategies to move the OCD field forward including: funding approaches, For all of these strategies, experts recommend facilitating collaboration in the field facilitating collaboration in the field recommend For all of these strategies, experts multi-disciplinary teams, and investing across data sharing, supporting through multiple sites. ƒ ƒ ƒ ƒ Strategies that philanthropists might use to move the field forward can include: might use to move the field forward Strategies that philanthropists ƒ ƒ ƒ Philanthropy can play specific roles in the effort to improve OCD outcomes, using OCD outcomes, improve the effort to roles in specific can play Philanthropy roles include that by experts. Those recommended and approaches defined strategies or a catalyst. a sustainer, of a connector, PHILANTHROPIC OPPORTUNITIES PHILANTHROPIC Current State of the OCD Field 6

2 1 5 The actual 4 ders (DSM-5) that 6 3 (ADHD), Tourette syndrome, depression, and other disorders. Another and other disorders. depression, syndrome, (ADHD), Tourette

7.7 percent of people. Schizophrenia affects 1 percent of the population, and post- affects 1 percent of people. Schizophrenia 7.7 percent of the population annually. affects 3.5 percent disorder traumatic stress 40 people in the U.S. having OCD during their lifetime. To put this in context, an 40 people in the U.S. having OCD during their lifetime. To Americans of Americans have mental illness, and 4.2 percent of estimated 18 percent which affects is anxiety, have serious mental illness. The most common disorder in their lifetimes, and about half of these cases are considered severe. considered in their lifetimes, and about half of these cases are with an estimated 1 in is slightly higher at 2.5 percent, of the disorder prevalence also begin later in life. diagnosed with OCD officially of adults in the United States are About 2 percent reason is the stigma and lack of understanding of the disorder among the public and among the public and the disorder is the stigma and lack of understanding of reason diagnosed in childhood or adolescence, OCD can Commonly medical professionals. high rate of comorbidity, often presenting with anxiety, attention deficit hyperactivity with anxiety, often presenting high rate of comorbidity, disorder population. is its of those reasons One for a number of reasons. OCD often goes undiagnosed While OCD is no longer considered an anxiety disorder, anxiety disorders and major anxiety disorders an anxiety disorder, While OCD is no longer considered in the general people with OCD than they are common in both more are depression edition of the Diagnostic and Statistical Manual of Mental Disor edition of the Diagnostic and to focus on obsessions and compulsions. revised the diagnostic criteria were year, distress, often interfering with work, school, and personal relationships. often interfering with work, distress, the publication of the fifth With an anxiety disorder. Until 2013, OCD was considered Obsessive compulsive disorder is a common psychiatric disorder characterized by a common psychiatric disorder is Obsessive compulsive disorder thoughts and behaviors that a person feels compelled to and uncontrollable recurring time consuming and cause significant These obsessions and compulsions are repeat. DEFINITION AND DIAGNOSIS DEFINITION field, barriers and opportunities. field, barriers To lay the groundwork for understanding the role philanthropy can play, it is can play, philanthropy for understanding the role lay the groundwork To state of the it is diagnosed, the overall how the disorder, important to understand OF THE OCD FIELD OF THE PART ONE: CURRENT STATE STATE CURRENT ONE: PART Current State of the OCD Field 7 ugs 9 CBT is a very effective treatment when treatment very effective CBT is a 7 for the disorder. 11 8 : In 2018, the U.S. Federal Drug Administration (FDA) approved : In 2018, the U.S. Federal Drug as potential treatments 10 Brain stimulation under investigation and Alternative methods for delivering CBT are Psychotherapy: therapy; use of technology including intensive, short-term the country, in use across such as acceptance & to deliver or augment therapy; and alternatives to ERP, bias modification. commitment therapy (ACT), inhibitory learning, and attention : A new class of medications for treating OCD may be on the horizon. new class of medications for treating A Medication: other than serotonin, for neurotransmitters a role has suggested Recent research now being that modulate glutamate signaling are such as glutamate, in OCD. Drugs evaluated (TMS) for use in OCD. the first medical device for transcranial magnetic stimulation (DBS). TMS is a noninvasive alternative to deep brain stimulation Second-line treatments include brain stimulation therapies. Approximately 60 percent 60 percent Approximately include brain stimulation therapies. Second-line treatments brain stimulation. Thus, to deep OCD respond of people with treatment-resistant but need appear to benefit some individuals with OCD, these second-line treatments and to determine how they can clinical testing to establish their safety thorough more be used most effectively. applied appropriately, but few providers are trained properly to administer properly trained are but few providers applied appropriately, developed 30 years ago, and were these first-line treatments Moreover, treatment. since. in highly effective treatments have been very few breakthroughs there ƒ by for OCD has been hampered treatments targeted Still, the development of new, a poor understanding of the disorder’s biological origins. While genetics clearly ƒ ƒ The field is developing several new treatments, which are explored in more detail in in more explored which are new treatments, The field is developing several Part Four of this paper. About one-third of patients with OCD do not experience a significant reduction in reduction of patients with OCD do not experience a significant About one-third second-line treatments. either first-line or established symptoms from However, appropriate application of these first-line treatments remains a challenge. remains a challenge. of these first-line treatments application appropriate However, dr may have to try several months to take effect, and patients SSRIs can take one that works for them. finding before First-line treatments for OCD include cognitive behavioral therapy (CBT)—exposure therapy (CBT)—exposure behavioral include cognitive for OCD treatments First-line reuptake selective serotonin therapy (ERP) in particular—and prevention response patients, but rarely symptoms for many reduce These treatments inhibitors (SSRIs). people with OCD could of 50 to 70 percent Experts estimate entirely. eliminate them if applied appropriately. first-line treatments be helped by current TREATMENT Current State of the OCD Field 8 in OCD. in OCD. ogress of research of research ogress 13 Neuroimaging studies, however, have have studies, however, Neuroimaging 12 Medical and mental health providers do not know enough to properly diagnose do not know enough to properly Medical and mental health providers with symptoms. OCD when a person presents have contributed to limited of the disorder and trivialization Low awareness other conditions that This contrasts with government funding for OCD research. lobbies, such and building strong have been successful in raising public awareness allocations of large and HIV/AIDS, which have generated cancer, as autism, breast U.S. government. funding by the research People with OCD often suffer from symptoms for a long time before seeking symptoms for a long time before from People with OCD often suffer treatment. ƒ ƒ ƒ The first of these factors is the low awareness and high stigma associated with and high stigma associated with low awareness The first of these factors is the and is less understood by the as a hidden disorder OCD is described the disorder. the Amongst illnesses. than other psychiatric public and many medical professionals undermining an understanding of the level public, OCD is often used colloquially, it. Experts believe lives of people who suffer from of disability it can cause in the impacts the field in a number of negatively about the disorder that lack of awareness ways: LOW AWARENESS AND HIGH STIGMA AWARENESS LOW CURRENT CHALLENGES IN ACCESS TO CARE TO ACCESS CHALLENGES IN CURRENT that have slowed the pr faces a number of challenges The OCD field and prevented more people with OCD from accessing and receiving effective accessing and receiving OCD from people with more and prevented for patients with describe access to effective treatment Indeed, experts treatment. in the field. It is a multi-dimensional challenge with a OCD as the leading challenge of and high stigma, a lack including low awareness variety of contributing factors, providers. and a lack of access to qualified effective treatments, influence who develops OCD, no single genetic factor has been found to confer has been found genetic factor OCD, no single who develops influence the disorder. of developing risk a strong provided compelling evidence of which brain circuits are impaired are circuits of which brain evidence compelling provided Researchers are beginning to refine their view of how these circuits are dysregulated dysregulated are circuits their view of how these beginning to refine are Researchers is still being developed. detailed knowledge more in OCD, although Current State of the OCD Field 9 r’s or prescribe established y were e . Consequently, r. Consequently, . From there, the there, . From r As noted earlier, most medical As noted earlier, date have been around second- date have been around e. currently are gation, though there or OCD since th ts f Most innovations to LY TRAINED PROVIDERS first-line treatmen rst-line treatments are slow to cause improvement in people slow to cause improvement are rst-line treatments faster treatments are under investi are faster treatments relieve symptoms. relieve which leaves patients under served when they could be helped by which leaves patients under served when they could be helped

changed with the Improvement is slow with current treatments. SSRIs and CBT/ERP take weeks CBT/ERP SSRIs and treatments. is slow with current Improvement And because the OCD field of symptoms. in a reduction or months to result unable to observe a diagnosis or set of clinicians are predictors, lacks treatment combination will be most effective. symptoms and know what treatment Though considered effective, ERP is a very structured therapy that requires specific requires therapy that is a very structured effective, ERP Though considered is a There patients. of compliance from and high levels training for providers, to because of access and willingness people into treatment—both challenge getting them compliant. keeping in treatment, commit—and once providers do not have the proper training to effectively deliver CBT/ERP providers do not have the proper training to effectively deliver SSRIs for OCD, graduates of Maste OCD are patients with the majority of people available to treat Those who are properly diagnosed enter a healthcare system that often funnels them system that often diagnosed enter a healthcare properly Those who are even less likely to have the are who to the least qualified, least expensive providers in academic doctoral right training. Most evidence-based clinical training takes place which each graduate only ten to fifteen people per yea programs, these treatments under the right circumstances. under the right circumstances. these treatments LIMITED ACCESS TO FUL TO LIMITED ACCESS is a dearth of trained lack of access is that there One significant factor in this OCD. Experts estimate who can accurately and fully diagnose and treat professionals misdiagnosed because front-line with OCD are of patients presenting that one-third doctors, nurses) and room doctors, emergency (e.g., primary care medical providers so often misunderstand the disorde mental health professionals 30 years ago. Because fi no quick fixes to protocols. or augment the effectiveness of current to enhance line treatments people with OCD, but many effective for more could be more treatments Current protocols. treatment that includes proper care patients do not have access to of clinical car challenges continue along the spectrum Very little has OCD, suffering from ƒ ƒ Current psychiatric treatments for OCD are considered very good. Experts estimate very good. Experts considered are for OCD treatments psychiatric Current if first-line treatments be helped by current of those with OCD could 50 to 70 percent no are for whom there to 50 percent that leaves 30 However, applied appropriately. effective below. pose some challenges as noted also treatments And, current treatments. LACK OF EFFECTIVE TREATMENTS OF EFFECTIVE LACK Current State of the OCD Field 10 therapy. therapy. siological complexity of OCD creates obstacles to the discovery of new treatments treatments obstacles to the discovery of new siological complexity of OCD creates the disorder, and research is hampered by a lack of access to the human brain. by a lack of access to the human is hampered and research the disorder, data on the brain or sophisticated does not yet exist that provides Technology associated with OCD, there is still a long way to go. associated with OCD, there implicated in the exact brain circuitry have not yet discovered Researchers behind many other mental health fields in terms of its human evidence base. Though behind many other mental health fields in terms of its human to the genes and brain circuitry years related strides in recent have made researchers First of these barriers is the complexity of the disorder. The biological and First of these barriers is the complexity of the disorder. phy The OCD field is wide swaths of people with the disorder. that will work across COMPLEXITY OF THE DISORDER COMPLEXITY micro-focused on disparate angles of investigation, with very little incentive to look at on disparate angles of investigation, with micro-focused the field. across the big picture of research. A number of factors contribute to the slow pace of progress toward toward contribute to the slow pace of progress number of factors A of research. people with OCD; and these barriers also keep the field more effectively treating SLOW PROGRESS ON RESEARCH ON PROGRESS SLOW the state significant challenge in furthering the field of OCD is second highly A raised to move more people to experiencing fewer symptoms. people raised to move more the field, treatment is considered successful with as little as a 25 percent reduction in successful with as little as a 25 percent is considered the field, treatment should be standards that this bar is too low and treatment symptoms. Experts argue LOW BAR FOR SUCCESS LOW Within is the low bar for success. treatment An additional limitation on adequate companies are low enough to avoid the insurance system all together, thereby further further thereby insurance system all together, low enough to avoid the companies are access. restricting are specially trained to properly administer ERP therapy most often do not take therapy most often do not administer ERP trained to properly specially are insurance is high enough and incentives from insurance. Demand for services Additionally, reimbursement rates in psychiatry do not follow the medical model, rates in psychiatry do not follow reimbursement Additionally, who those providers specialists at higher rates. Therefore, which reimburses A second major restriction on access to the right providers and protocols is a lack and protocols the right providers on access to second major restriction A providers do not reimburse Most insurance companies of insurance coverage. administer CBT/ERP number of sessions to effectively for an adequate to treat the two million people diagnosed with OCD. people diagnosed the two million to treat level programs, and thus have less rigorous training. Experts estimate that there are are that there Experts estimate training. less rigorous and thus have level programs, enough not nearly is States, which in the United trained providers properly only 1,500 Current State of the OCD Field 11 der in typical but because the genetic factors that contribute to OCD are that contribute to OCD are but because the genetic factors 14 In other fields (e.g., schizophrenia, autism, bipolar, and depression), and depression), autism, bipolar, In other fields (e.g., schizophrenia, 15 much larger sample sizes. much larger Experts note that if the field finds better ways of studying the disor Experts note that if the field finds better ways of studying with multiple diagnoses, they would most likely have access to patients who present across sites prevents researchers from accessing patients in multiple locations. The from researchers sites prevents across for studies. difficult to find “clean” samples comorbidity of OCD also makes it more Getting the necessary sample sizes is difficult because researchers often lack access researchers Getting the necessary sample sizes is difficult because may have sophisticated labs, but Researchers to enough people with the disorder. the lack of collaboration Additionally, access to clinics and people. they lack direct see large effect sizes. see large and postmortem studies would be beneficial. For genetics research, because so many because so research, be beneficial. For genetics and postmortem studies would to necessary in order sample sizes are large implicated in OCD, extremely genes are As discussed above, advances in understanding the brain circuitry of OCD are of OCD are in understanding the brain circuitry As discussed above, advances by small post-mortem brain by limited access to the human brain and hampered samples sizes for neuroimaging much larger field further faster, move the studies. To In order to make breakthroughs in understanding the basic biology and physiology in understanding the basic to make breakthroughs In order have been available. sample sizes than much larger require of OCD, researchers SMALL SAMPLE SIZES SMALL SAMPLE causing large effect sizes, which has allowed them to create better animal models to to create effect sizes, which has allowed them causing large very limited in the field of OCD. Publications on this kind of work are study. likely to be of small effect individually, much larger studies may be needed to much larger likely to be of small effect individually, find them. with single gene mutations have made advances by identifying families researchers (variants located in or near the genes ASB13, RSP04, DLGAP1, PTPRD, GRIK2, RSP04, DLGAP1, PTPRD, GRIK2, ASB13, in or near the genes (variants located and CDH20), FAIM2 from both studies included 2,688 individuals with OCD and 7,037 controls. In this and 7,037 controls. 2,688 individuals with OCD both studies included from with OCD significant associations some variants showed minimally meta-analysis, for OCD. Two genome-wide association studies (GWAS) have compared the DNA the DNA have compared studies (GWAS) genome-wide association for OCD. Two that associate with of variants in search with and without OCD sequences of people meta-analysis pooled A later inconsistent. and their findings were the disorder, Moreover, while OCD is a genetic disease, the field has yet to identify genetic markers has yet to identify genetic markers is a genetic disease, the field while OCD Moreover, effectively studies the brain in real time, leaving researchers to rely on neuroimaging, on neuroimaging, rely to researchers leaving real time, brain in studies the effectively animal models. and imperfect is minimal), (which brain research post-mortem Current State of the OCD Field 12 gest barriers in the gest barriers NIMH funding is very slow. It typically takes more than one year from grant than one year from takes more It typically NIMH funding is very slow. funding. submission to receive forcing studies, of proposed the full breadth NIMH grants often do not cover back studies. or to scale to piece together multiple funding sources researchers NIMH funding priorities often change, forcing researchers to adapt their proposals researchers change, forcing NIMH funding priorities often arise. to match new priorities as they NIMH tends to fund low-risk research. NIMH tends to fund low-risk limiting the not big enough to support multi-site collaboration, NIMH grants are scale and scope of studies. genetic specific targeting research to fund For animal studies, NIMH prefers for OCD, because genetic markers haven’t been identified markers. However, difficult to secure. funding is more e of researchers entering e of researchers Many of the factors outlined above contribute to a weak pipelin enter the field researchers in a dozen new the OCD field. Experts estimate that perhaps the numbers for other psychiatric fields. which is smaller than the United States annually, in the choosing to build a career The lack of available funding disincentivizes people from the International for young investigators through field, though smaller grant programs Foundation have been somewhatOCD Foundation and the Brain and Behavior Research who do decide to enter the field, to get started. successful in helping those researchers INSUFFICIENT PIPELINE OF RESEARCHERS ƒ for constant search conclude that the lack of funding keeps them in a Researchers big grant to grant, rather than being able to fully explore new funding, moving from from also keeps researchers ideas over time. Competition for limited funding picture research. especially on cross-discipline effectively, and more often collaborating more ƒ ƒ ƒ ƒ ƒ Experts further note the following challenges presented by the current state of NIMH state by the current presented note the following challenges Experts further funding: OCD research field. As explored more fully in Part Three of this report, NIMH is the of this fully in Part Three more As explored field. OCD research does not officially United States. While NIMH in the of OCD research leading funder conducted by NIMH an unofficial search for OCD in their database, categorize funds $19 million in 2008 to from OCD increased funding going toward shows that research field is that NIMH in the researchers the experience of 2018. However, $28.1 million in restrictive. more to get and has become harder funding, specifically, Experts observe that lack of access to funding is one of the lar funding is one of access to observe that lack Experts FUNDING Current State of the OCD Field 13

18 boration is not common. boration is not 16 The NIH grant funds ran out in 2018, and the group is The NIH grant funds ran out in 2018, and the group 17 ATION currently in search of funding so that it may convene an in-person conference and of funding so that it may convene an in-person conference in search currently now volunteering. pay staff, who are : Based in the U.S., the IOCDF Research Symposium is an annual and goal: Based in the U.S., the IOCDF Research Background The OCD Conference. one-day symposium, held in conjunction with a four-day : In 2014, Dr. Paul Thompson received four years of NIH funding for Paul Thompson received Funding: In 2014, Dr. its annual budget to $70,000, to professionalize, ENIGMA, which enabled it to grow member. a staff and to hire : All sites contribute data to the collaborative studies, and the group largely All sites contribute data to the collaborative studies, and the group Activities: has published The group email and teleconferencing. collaborates virtually through with OCD. major publications on brain abnormalities associated three ENIGMA currently includes 200 researchers, representing 32 research representing includes 200 researchers, currently Membership: ENIGMA A. van den Odile by Dr. chaired is currently group 16 countries. The from groups University Medical Center. Amsterdam Heuvel of the : This international, Amsterdam-based group was founded group Amsterdam-based and goal: This international, Background the challenge of small study populations for OCD resulting in 2010 to address groups research OCD has the goal of bringing findings. ENIGMA in unreliable databases. and genetic neuroimaging together to share International OCD Foundation (IOCDF) Research Symposium Research (IOCDF) OCD Foundation International ƒ ƒ ƒ ƒ ƒ ENIGMA OCD Working Group ENIGMA OCD Working Despite this general consensus regarding collaboration, there are several notable Despite this general consensus field: platforms promoting collaboration in the Experts note that genetics researchers actively collaborate the most, likely due to the actively collaborate the genetics researchers Experts note that sites. access to data and patients across sample sizes, which requires need for larger clinicians happens at to sharing between researchers Collaboration and information discoveries and research recent of clinicians well aware the highest levels, with senior is a major disconnect between Beyond that, there implications for clinical practice. findings and clinical care. research Small NIMH grant sizes make multi-site collaboration difficult, and competition for and competition difficult, sizes make multi-site collaboration Small NIMH grant actively pursuing from keeps researchers NIMH and other sources funding from collaboration barriers removed, believe that with funding collaboration. Experts benefit the field. and would significantly common more would be much LOW COLLABOR LOW 100 leading fewer than estimating is small, with experts field research The OCD themselves as very collegial United States. Experts characterize in the researchers actual colla collaborate, but point out that and willing to Current State of the OCD Field 14 : In 2018, ICOCS had 45 participants at its conference. : The Symposium attracted 50 participants in 2016 and 2017 respectively, attracted 50 participants in : The Symposium 19 goal is for researchers to discuss their findings with one another, to network, and to another, with one their findings to discuss researchers goal is for by Christopher chaired Symposium is The collaboration.” increased to “foster The PhD (Stanford). Rodriguez, MD, and Carolyn MD, PhD (Yale) Pittenger, has in 2018, and the Symposium marked its 25th year Conference attendant OCD years. past three for the been running Attendance across (conducted virtually Activities: Undertakings include collaborative research American journals, convenings and sites), publications in primarily European the building and maintenance of an international America and Europe), (North countries), 11 across database of patient data (clinical and demographic data from (ECNP) network College of Neuropsychopharmacology and managing a European Background and goal: Based in the U.K. near London, the ICOCS is an international Background among projects research to stimulate and coordinate created member organization Annual meetings have of OCD. public health awareness members, and to increase been held since 2006. : The majority of the day consists of numerous 10 to 20 minute of numerous Activities: The majority of the day consists and followed by a moderated discussion among researchers presentations, by topic (e.g., organized are Presentations attendees led by a senior researcher. providing outcomes”), and treatment “factors affecting OCD presentation initiatives. IOCDF’s primary the opportunity to connect on related researchers opportunities to network (formally and is to provide to collaboration approach mentoring/professional/ Q&A, a speaker reception, poster informally through to foster An additional approach trainee meet-ups, and social gatherings). participants to join the Scientific and Clinical collaboration includes encouraging (e.g., the Genetics groups (50 members) and special interest Advisory Board Collaborative). Attendance in 2019. for 125 to 150 participants in 2018. IOCDF is planning and 100 participants (including nearly 2,000 attendees in 2018 had OCD Conference For context, the with OCD or a related people living researchers, mental health professionals, and friends/family members). disorder, ƒ ƒ ƒ International College of Obsessive Compulsive Spectrum Disorders Spectrum Disorders Compulsive Obsessive of College International (ICOCS) ƒ ƒ Current State of the OCD Field 15 The ECNP is a scientific multi-disciplinary pan-European pan-European multi-disciplinary is a scientific The ECNP 20 platform for research collaboration that is primarily focused on data collection on data collection primarily focused that is collaboration for research platform diseases. to specific related focused on OCD. focused : The organizational budget is supported primarily by membership fees, budget is supported Funding: The organizational grant funding. with additional ƒ Ecosystem of Research Stakeholders 16 Funding for OCD is 24 Even with such a large Even with such a large 21 In 2018 (as of September), NIMH In 2018 (as of September), NIMH 22

Below are the current options (or “series”) for investigator-initiated grants, which fall (or “series”) for investigator-initiated options the current Below are fellowships and (K series); awards grants (R series); career into categories of: research series). and center grants (P project program training grants (F and T series); research GRANTMAKING STRUCTURES for proposals. either “investigator initiated”, or by requests At NIMH, grants are significantly less than that for other disorders or conditions. other disorders significantly less than that for and only 20 percent of applications are funded. of applications are and only 20 percent of $27 million. to OCD for a total related funded 72 projects In FY 2018, NIMH operated with a budget of $1.6 billion. 2018, In FY funding. that request projects a portion of research budget, NIMH can only fund percent— by 75 for NIMH funding increased Since 1988, the number of applications FUNDING AMOUNTS FUNDING AMOUNTS In the field of mental health and disorders, NIMH, the U.S. National Institute of NIMH, the and disorders, In the field of mental health in the world. funder of research Mental Health, is the largest GOVERNMENT three major stakeholder groups currently in a prime position for moving the research field moving the research in a prime position for currently groups major stakeholder three institutions. and research government, philanthropy, forward: include government, philanthropy, research institutions, mental health care providers, mental health care institutions, research philanthropy, include government, section focuses on advocates, and educators. This patients, families, community groups, The diverse stakeholder groups comprise a robust ecosystem of players with an interest ecosystem of players with comprise a robust groups The diverse stakeholder OCD field. Stakeholder groups and practice within the in advancing knowledge RESEARCH STAKEHOLDERS RESEARCH PART TWO: ECOSYSTEM OF ECOSYSTEM TWO: PART Ecosystem of Research Stakeholders 17 DESCRIPTION Research education mentoring programs for HIV/AIDS education mentoring programs Research Fosters the development of mental health researchers via Fosters the development of mental health researchers educational programs and innovative research creative as well as and national programs including regional a single institution involving programs education research Short courses for mental health-related supporting psychiatric education programs Research residents education Mentoring networks for mental health research AREA grants create opportunities for scientists and grants create AREA extensively institutions, otherwise unlikely to participate to contribute to the nation’s programs, in NIH research effort biomedical and behavioral research research Encourages exploratory and developmental by providing scientific areas in all NIMH-relevant projects stages of these support for the early and conceptual projects and/or environments research Supports strengthening in all expanding existing capacities for conducting research related to mental health fields Two or more sites needed to complete the study more or Two Pilot or feasibility studies Secondary analysis of existing data projects Small, self-contained research methodology Development of research technology Development of new research Provides support for health-related research support for health-related Provides performed by one or more a project Supports grants for named investigator(s) award Longer-term trials in the treatment, Collaborative intervention disorders of those with mental or rehabilitation prevention disorders and comorbid mental genetics, and AIDS, research, Mental health services psychopathology ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ $ AMOUNT $275,000 over 2 years, with no single year exceeding $200,000 Case-by-case Case-by-case Up to $50,000 per year $500,000+ across $500,000+ across 2+ sites per year $300,000 for up to (not years three per year) Up to $250,000 per year for up to five years GRANT TYPE OF TYPE OF NIH Exploratory/ Developmental Grant Research (Parent Program R21) NIMH Research Infrastructure Support Program (R24) NIMH Research Education Grants (R25) Small Research Small Research Grant (R03) Academic Research Enhancement (R15) Award Collaborative Grants for Clinical and Services Studies of Mental Disorders AIDS and (Collaborative R01) Research Project Project Research Grant (Parent R01) Types of Investigator Initiated Research Grants at NIMH at Grants Research Initiated Investigator of Types 1. TABLE Ecosystem of Research Stakeholders 18 DESCRIPTION Center Core Grants (P30): Supports shared resources and resources Grants (P30): Supports shared Center Core investigators of number a by research categorical for facilities a multidisciplinary disciplines who provide different from the same effort or from research to a joint approach problem discipline who focus on a common research Specialized Center (P50): Supports any part of the full range very basic, to clinical and development from of research Same as K grants above within the research training programs Support research NIMH priorities supported by and research areas and fees, and training- Offsets the cost of stipends, tuition expenses including health insurance for the related appointed trainees (P01): Supports a multi- Projects Program Research program disciplinary long-term research Support small businesses to develop technologies that can Support small businesses to develop advance the mission of NIMH translational research, Can include basic neuroscience diagnosis and treatment, clinical and clinical research, of evidence-based and dissemination and implementation on mental disorders research phase process Includes a three of early-stage capital for sources One of the largest States in the United technology commercialization Resources for evaluating the feasibility, tolerability, the feasibility, for evaluating Resources to improving safety of novel approaches acceptability and modifying health risk behavior mental health and as data needed the preliminary for obtaining Resources (efficacy or effectiveness) to a larger-scale a prerequisite study intervention or services for pilot study of innovative Collaborative grants disorders in mental health treatments training and for research researchers Grants to individual in to mid-career predoctoral from development, career diversity; workforce to enhance of (1) programs the areas (2) for physician-scientists and other clinician- programs loan repayment and scientists; (3) institutional programs, ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ $ AMOUNT Case-by-case Up to $675,000 annually for up to 5 years (P01) Up to $1.75M (P30) Up to $2M per year for 5 years (P50) $1 million for prototype development (phase 2) Case-by-case Grant calculated based on salary; maximum award size is $300,000 faculty for direct Up to $150,000 for concept development (phase 1), up to Case-by-case GRANT TYPE OF TYPE OF Training- Institutional Fellowships (T) Project Program Grants/Center Grants (P) (these exist currently only for study of HIV/AIDS) Training- Individual Fellowships (F) Research Career Career Research Development Grants (K) Small Business Grants (R) Exploratory Exploratory Clinical Research Grants (R34) Ecosystem of Research Stakeholders 19 This amount includes support This amount includes support 25 Community events and programs such as an annual OCD Conference, OCD such as an annual OCD Conference, Community events and programs (ambassadors for and an OCDvocates program OCD Walks, Week, Awareness IOCDF). Educational resources in the forms of newsletters, fact sheets, handouts, brochures, in the forms of newsletters, fact sheets, handouts, Educational resources and websites. of health care services and facilities, mental health and crisis intervention, diseases services and facilities, mental health and crisis intervention, of health care has not the mental health field Historically, research. and medical and disorders, causes, gifts as other health-related philanthropic attracted the same kinds of large leading underfunded. This section outlines some of the relatively and OCD remains field. entities working specifically within the OCD philanthropic ƒ ƒ IOCDF’s activities are varied and include: IOCDF’s activities are Founded in 1986 “to help everyone affected by OCD and related disorders to live related disorders Founded in 1986 “to help everyone affected by OCD and end access to effective treatment, lives,” IOCDF aims to increase full and productive a community for those the stigma associated with mental health issues, and foster is based in the U.S. them. IOCDF who treat affected by OCD and the professionals global partnerships. and has affiliates in 25 states and territories, in addition to INTERNATIONAL OCD FOUNDATION (IOCDF) OCD FOUNDATION INTERNATIONAL In 2016, approximately eight percent of all philanthropic giving in the United States giving in of all philanthropic eight percent In 2016, approximately causes. health-related ($33.1 billion) went toward PHILANTHROPY In general, NIMH RFP grants are dictated by “the needs of the field,” and NIMH the field,” and “the needs of dictated by grants are NIMH RFP In general, noted that they are for OCD grants. NIMH interviewees an RFP has never issued have previously for OCD—and over other research treatment most likely to fund reduce medications while could whether individuals studies (specifically, funded ERP as specifically focused NIMH does not code its grants treatment). ERP participating in as a keyword for active grants with “OCD” of its database a search on OCD, though funding NIMH is currently grants made in 2017 and 2018. for results 110 returns 51 of NIMH’s current not all OCD specific, Although on OCD. two DBS trial studies and include research and brain networks, on neural circuits focused are projects of serotonin regulation receptors, of NDMA on topics such as the modulation in pediatric OCD cases. While many of these studies transporters, and brain functions OCD, they may the total amount of funding toward may not be counted toward field. contribute to advances in the CURRENT OCD-RELATED NIMH GRANTS OCD-RELATED CURRENT Ecosystem of Research Stakeholders 20 ding e also offered. DESCRIPTION For researchers with at least five years of experience For researchers and for OCD; could include prevention Focus on finding a cure treatment as of 2018 New award with at least five years of experience For researchers and for OCD; could include prevention Focus on finding a cure treatment For researchers in graduate school or with up to five years of For researchers experience research body disorder, hoarding Focus on OCD, PANS/PANDAS, dysmorphic disorder as of 2019 New award ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ AMOUNT $500,000 $300,000 Up to $50,000 for one year TYPE A genetics collaborative, which is an international group of 50 genetics investigators is an international group genetics collaborative, which A samples, DNA findings and and share to foster collaboration who convene annually causes of OCD. goal of identifying the genetic with the ultimate Pediatric outreach programs aimed at raising awareness and providing general and providing awareness aimed at raising programs Pediatric outreach OCD. education around A training institute that provides a curriculum of professional training of professional a curriculum provides institute that training A OCD. The people with treating health professionals for mental opportunities which trains Institute (BTTI), Training Therapy is the Behavior program flagship Online courses ar for adult and pediatric patients. clinicians in CBT Breakthrough Breakthrough Award Innovator Award Young Young Investigator Award grants that will lead to advances and breakthroughs in scientific research. It is the research. in scientific grants that will lead to advances and breakthroughs Founded in 1987, nation’s top non-governmental funder of mental health grants. than $394 more illnesses, one of which is OCD, and has awarded BBRF funds 11 BRAIN & BEHAVIOR RESEARCH FOUNDATION (BBRF) RESEARCH FOUNDATION BRAIN & BEHAVIOR illness by awar BBRF’s mission is to alleviate the suffering caused by mental Recent grantees have focused across approaches, including genetics, ERP therapy, therapy, including genetics, ERP approaches, Recent grantees have focused across Americans, for African and diversity (OCD symptoms in new technology treatments, recently IOCDF, grant ever from the largest Award, example). The first Breakthrough will The award the University of Pittsburgh. Ahmari from to Susanne was awarded sample of post-mortem brain tissue support her study of molecular changes in a rare more patients with OCD. The goal is to pave the way for development of new, from for OCD. effective pharmacological treatments As of 1994, IOCDF has awarded $3.5 million total in research grants. It operates a total in research $3.5 million As of 1994, IOCDF has awarded as outlined below. program, award research tiered Research Grants Research ƒ ƒ ƒ Ecosystem of Research Stakeholders 21 BBRF’s featured OCD researchers include OCD researchers BBRF’s featured 26 Dr. Susanne Ahmari (University of Pittsburgh), who won a Young Investigator Young who won a Ahmari (University of Pittsburgh), Susanne Dr. award brain stimulation on mouse in 2012 for her studies on the use of deep models. Dr. H. Blair Simpson (Columbia University), who serves as an expert on OCD to the H. Blair Dr. trial to test whether for her work on a clinical and won two awards organization to CBT and an imaging study adherence motivational interviewing could increase glutamate in a part of the brain called the stratum. to measure Dr. Carolyn Rodriguez (Stanford University), who won Young Investigator grants Young who won University), Rodriguez (Stanford Carolyn Dr. in 2009 and 2014 for her studies on rapid-acting treatments. Young Investigator: Two-year award of up to $70,000 total. of up to $70,000 award Investigator: Two-year Young $100,000 total. of up to award Independent Investigator: Two-year of $100,000. award Distinguished Investigator: One-year early interventions/diagnostic tools; and early interventions/diagnostic of mental illness and work symptoms reduce next generation therapies to help prevention. towards basic research; new technologies; ƒ ƒ ƒ ƒ focused on study $4 million to OCD. One recent Since 1987, BBRF has awarded in the cortex with OCD; another examined differences of people the neurocircuitry OCD. between people with and without ƒ ƒ The types and amounts of grants are: The types and amounts of grants ƒ ƒ ƒ ƒ Rather than issuing RFPs, BBRF uses its internal scientists and its scientific council to scientists and its scientific RFPs, BBRF uses its internal Rather than issuing categories include: award Research select grantees. Research Grants Research million to fund more than 5,700 grants. BBRF funds “the most innovative ideas most innovative funds “the grants. BBRF than 5,700 to fund more million and develop new the causes better understand psychiatry to and in neuroscience National known as BBRF is formerly disorders.” and behavior brain treat ways to (NARSAD). and Depression on Schizophrenia Research Association for several of those interviewed during the research for this publication: for the research several of those interviewed during Ecosystem of Research Stakeholders 22

27 esearch is conducted is conducted esearch This is an example of how 28 brain functions and several disorders, including OCD. brain functions and several disorders, efforts. research be subsumed within larger OCD may funding towards Other foundations include the Henry L. Hillman Foundation, which granted $600,000 Other foundations include the researching studies numerous Brain Institute to launch to the University of Pittsburgh Científico e Tecnológico (CNPq) in Brazil and Fondation FondaMental (FFM) in (CNPq) in Brazil and Fondation FondaMental (FFM) Tecnológico Científico e OCD is unknown. goes towards for OCD, but the amount that France fund research Globally, research institutes such as the Conselho Nacional de Desenvolvimento institutes such as the Conselho Nacional research Globally, an institution that they personally connect to (e.g. because their family member was (e.g. because their family member they personally connect to an institution that there). treated Private family philanthropic dollars towards OCD tend to come from families with OCD tend to come from dollars towards philanthropic Private family or researcher fund a funders often circumstance, In this member. an affected family under the auspices of larger studies. Those sources include private funding, global include sources studies. Those of larger under the auspices funders. funding, and other There are several other funding sources available for OCD, though determining determining for OCD, though available sources other funding several are There reporting, OCD is often OCD is difficult. In going toward total funding amounts (e.g., anxiety) and r a subset of another condition categorized as OTHER FUNDERS OTHER Ecosystem of Research Stakeholders 23 PHILOSOPHY remission and recovery from OCD. OCD. from and recovery remission integrates genetics, The program neurophysiology, neuroscience, to and clinical research technology, OCD understand, assess, and treat disorders.” and related immunological and circuit/network immunological and circuit/network science to develop new and better and device based behavioral drug, interventions for OCD. understanding of Apply improving neurocircuitry and phenotypes OCD and research. to treatment believe in the integration “We and clinical care of research, education, with many faculty being Our active in all these spheres. ameliorative, are treatments current needs to be learned more however, and the treatment to provide our patients need.” that prevention ultimate goal is “Our program’s To provide state-of-the-art care state-of-the-art care provide To for OCD today and develop the using a of tomorrow treatments approach research two-pronged that combines molecular/genetic/ DIRECTOR(S) Wilhelm, PhD Wilhelm, Benjamin MD Greenberg, PhD (Butler) and Jennifer Freeman PhD (Bradley Hospital, pediatric OCD) Nestadt, Gerald MBBCh MPH Sabine Wayne Wayne Goodman, MD and Eric Storch, PhD 1980 1986 2016 1983 YEAR FOUNDING NAME OF OCD CENTER(S) OCD and Related Disorders Program Hospital/ Brown University OCD Research Program Johns Hopkins OCD Clinic BCM OCD Program Butler Leading US OCD Research & Treatment Institutions & Treatment US OCD Research Leading INSTITUTION School Harvard Harvard Medical Massachusetts General Hospital/ Institution Johns Hopkins Medical Hospital Butler Hospital, Bradley Brown Brown University, Baylor College of Medicine TABLE 2. TABLE considered leaders in OCD research and treatment in the United States and were and were in the United States and treatment leaders in OCD research considered for this report. included in analysis There are many universities, hospitals, and other mental health care facilities working facilities working care mental health and other universities, hospitals, many are There are The following institutions innovate within the OCD field. and to diagnose, treat, INSTITUTIONS Ecosystem of Research Stakeholders 24 PHILOSOPHY “We have a broad team of have a broad “We and genetic basic neuroscience as focusing on OCD, researchers and genetic well as neural circuits to OCD-related mechanisms related combines behaviors. Our work neural biology, cell and molecular and neuroimaging, and circuit approaches genetic and epigenetic variety of complementary a across experts.” DIRECTOR(S) Diane Davey, Diane Davey, RN, MBA, Program OCDI Director, Mark Picciotto, PhD, Program OCDI Director, Junior Kathryn Boger, PhD, Program Director, McLean Anxiety Mastery Program (MAMP) Mona Potter, MD, Medical Director, MAMP Kerry Ressler, Kerry Ressler, MD, PhD, Chief Scientific Officer and Chief, CoE for Depression Anxiety and Disorders 1997 2015 OCD OCD YEAR program) (pediatric program); program); (residential (residential FOUNDING NAME OF OCD CENTER(S) Mastery Program (MAMP) ODCI Center for Depression, Anxiety and Stress Disorders Research Center McLean Anxiety Neuroscience Neuroscience Clinical and research treatment: OCD Institute (OCDI) Child and Adolescent Basic research: Basic research: Center of for Excellence Depression Anxiety and Disorders Center of Excellence in Basic INSTITUTION Corporation The McLean Hospital Ecosystem of Research Stakeholders 25 PHILOSOPHY “UCSF does not currently have an “UCSF does not currently poised to but we are OCD center, a bottom- pursue, simultaneously, focused on discovery up approach de novo genetic large-effect of rare mutations as well as a top-down focused on enhanced, approach closed loop DBS.” Combining medication CBT, Combining medication CBT, non-invasive brain stimulation (magnetic and ultrasonic) for patients. resistant treatment Intensive inpatient and day (CB) and eventually DBS treatment for non-responders. Stanford’s Department of Psychiatry Psychiatry of Department Stanford’s aims and Behavioral Sciences mental illness. Its OCD to cure and clinical programs research diagnosis aim to transform the of people with and treatment translation of OCD by catalyzing into evidence- research neuroscience based, novel therapeutics. DIRECTOR(S) MD, PhD Jamie Feusner, MD Michelle Craske, PhD John Piacentini, Ph.D. N/A rolyn Carolyn Dr. Rodriguez Elias Dr. Aboujaoude Nolan Dr. Williams Alan Dr. Schatzberg Alexander Bystritsky, 2015 1989 2015 2008 1986 N/A YEAR FOUNDING NAME OF OCD CENTER(S) N/A Stanford Stanford Translational OCD Research Program Stanford OCD Clinic Stanford Brain Stimulation Lab Stanford Mood Disorders Clinic UCLA UCLA Anxiety and Related Disorders Program OCD UCLA Program UCLA Anxiety Behavioral Research Center Child UCLA OCD and Anxiety Program INSTITUTION University of California San Francisco (UCSF) Stanford Stanford University University of California Angeles. Los Semel Institute of Neuroscience and Human Behavior Ecosystem of Research Stakeholders 26 PHILOSOPHY new insights into genetics, and psychology to neurobiology, of pave the way for the treatments tomorrow.” program at Pitt is relatively new at Pitt is relatively program but rapidly expanding due to key in the past faculty recruitments is 5 years. Because our program young, nimble, and still relatively small, we have a tightly-knit and collaborative community that is thinking outside of the creatively box to try to develop new treatment for OCD, capitalizing approaches in bidirectional on unique strengths translation between humans and animal models, invasive and non-invasive neuromodulation and human approaches, treatment post-mortem research.” simultaneously pursue “We short-, medium-, and long-term goals: short term entails getting out with today’s treatments fidelity; medium is using today’s understanding to develop new and long is developing treatments; “Our philosophy and mission is to “Our philosophy evidence-based treatment provide structured for OCD, which is also flexible and manualized, but individual to accommodate for recovery their during differences we Additionally, wellness. towards at increasing conduct studies aimed effectiveness of the efficacy and treatment.” “Although clinical excellence in the of OCD is a longstanding treatment tradition at the University of the OCD research Pittsburgh,

DIRECTOR(S) Christopher Pittenger Susanne Ahmari, MD, PhD Mark Richardson, MD, PhD* Christopher Pittenger Michael Bloch Fernandez Tom Edna B. Foa, PhD Bob Hudak, MD

1990 2007 1984 1998 2014 2013 1979 YEAR FOUNDING NAME OF OCD CENTER(S) Research Research Clinic Child Yale Study Center Tic/OCD Clinic Pittenger Basic Science Laboratory Laboratory OCD Yale OCD Intensive Outpatient Program Translational OCD Laboratory Brain Modulation Center for Treatment the and Study Anxiety of (CTSA) INSTITUTION Yale Yale University University of Pittsburgh University of Pennsylvania *Mark Richardson, MD, PhD was previously a member of the OCD team the University of Pittsburgh at the time of this report, at the time of this report, team the University of Pittsburgh a member of the OCD MD, PhD was previously *Mark Richardson, but he has since moved to MGH.

Ecosystem of Research Stakeholders 27 PEDIATRICS

   BRAIN STIMULATION BRAIN

    MEDICATION

     PSYCHOTHERAPY

     TREATMENT (GENERAL) TREATMENT

           GENETICS

     NEURAL CIRCUITS NEURAL

    NEUROIMAGING           

AREA(S) OF EXPERTISE ANIMAL MODELS ANIMAL   INSTITUTION University of California, Los Angeles Massachusetts General Hospital University of California, Los Angeles University of Pennsylvania Baylor College University of Florida Johns Hopkins Massachusetts General Hospital University and Harvard Columbia University Center for Obsessive Compulsive Disorders Related and Treatment University of California, Los Angeles Rogers Behavioral Health University Stanford University of California, San Francisco University of Pittsburgh Yale University Yale Baylor College Massachusetts General Hospital University and Harvard NAME Alex Bystritisky, MD, PhD Alex Bystritisky, MD, MMSc Darin Dougherty, MD Jamie D. Feusner, Edna Foa, PhD Goodman, MD Wayne Mathews, MD Carol Gerald Nestadt, MBBCh, MPH Scharf, MD, PhD Jeremiah Helen Blair Simpson, MD, PhD John Piacentini, PhD Bradley C. Riemann, PhD Rodriguez, MD, PhD Carolyn Matthew State, MD, PhD Susanne Ahmari, MD, PhD Susanne Christopher Pittenger, MD, PhD Christopher Pittenger, PhD Alan Storch, Eric Sabine Wilhelm, PhD Sabine Wilhelm, Top OCD Researchers and Their Specialties and Their Researchers OCD 3. Top TABLE RPA interviewed the following top researchers throughout the field, selected based on the field, selected throughout top researchers the following interviewed RPA Their top OCD of our research. the course during as leading researchers their emergence in other specialties. also do work each may highlighted, though are of expertise areas RESEARCHERS Emerging Research 28 30 29 RESEARCH ndings, and what’s next in research and treatment and treatment next in research ndings, and what’s G N GI R

THREE: RT

We Know

ME Smaller studies have found the caudate nucleus, a structure in the striatum of the Smaller studies have found the caudate nucleus, a structure be smaller in people basal ganglia that is involved in the acquisition of habits, to abnormalities in the cortex and Other structural with OCD than in healthy controls. thalamus have also been reported. The ENIGMA OCD Working Group conducted the largest analysis of brain conducted the largest Group OCD Working The ENIGMA to date, comparing MRI scans of 1,905 OCD patients and 1,760 in OCD structure collected at multiple sites. The study concluded that the most healthy controls in the parietal cortex, occurred significant abnormalities in both adults and children of the brain. in the back a region ƒ

ƒ PA

c research has confirmed, scientific research origins of OCD have not been While the exact affected. The following section in the genes and brains of those pointed to differences fi recent know, maps what we E Magnetic resonance imaging (MRI) and computed tomography (CT) scans have imaging Magnetic resonance between the brains of people with abnormalities indicated a variety of structural but findings have been inconsistent among studies. OCD and healthy controls, Recent findings What What and function in people examining the brain’s structure studies Most neuroimaging within processing cognitive and emotional impaired with OCD have pointed toward carry information in These circuits (CSTC) circuits. cortico-striatal-thalamic-cortico processes most higher cognitive the cortex, where a loop that begins and ends in have been observed CSTC circuits Abnormal patterns of activity within take place. state, as well as when affected brain is in a resting in people with OCD while the stimuli that activate the circuits, exposed to tasks or are individuals perform cognitive OCD symptoms. including those known to trigger NEURAL CIRCUITS SCIENCE discoveries throughout the field. discoveries throughout Emerging Research 29 coming Conversely, other Conversely, epeated activation 40 Circuits involving the Circuits 33 Based on neuroimaging findings, Based on neuroimaging 38 Some, but not all, studies have also Some, but not all, studies have 34 parts of the brain involved in memory and emotion. in memory the brain involved parts of 31 39 32 Elevated activity in these regions has been found to decrease after found to decrease has been Elevated activity in these regions 37 These experiments suggest potential therapeutic strategies for over These experiments suggest potential therapeutic strategies 35, 36 41 orbitofrontal cortex are thought to be involved in context-related processing to be involved in context-related thought cortex are orbitofrontal closely the anterior cingulate has been more inhibition, whereas and response processing. tied to emotion and reward treatment for OCD, supporting the idea that these circuits mediate patients’ the idea that these circuits for OCD, supporting treatment symptoms. Functional MRI during symptom provocation also indicates abnormalities within also indicates abnormalities provocation Functional MRI during symptom in patients with OCD. cortex the orbitofrontal Functional imaging studies have consistently reported that patients with OCD reported studies have consistently Functional imaging cortex, the of the brain’s regions high levels of activity in two have unusually cingulate cortex. cortex and the anterior orbitofrontal Beyond CSTC circuits, structural abnormalities have been observed in the have been abnormalities structural CSTC circuits, Beyond and amygdala, hippocampus it has been proposed that dysfunction within CSTC circuits in people with OCD in people that dysfunction within CSTC circuits it has been proposed which information passes an imbalance between two pathways through arises from pathway and an excitatory cortex: a direct, thalamus to the brain’s frontal the from inhibitory pathway. indirect, found elevated resting activity in the basal ganglia, another component of CSTC activity in the basal ganglia, another component of found elevated resting circuits. With a newer method of MRI called diffusion tensor imaging, researchers have also have researchers tensor imaging, called diffusion method of MRI a newer With abnormalities) (known as microstructural small-scale defects detected widespread brain in areas of the different how information passes between that may affect people with OCD. researchers have found they can successfully suppress excessive grooming in a excessive grooming they can successfully suppress have found researchers within the CSTC mouse model of OCD by activating specific inhibitory connections circuitry. Researchers are now taking advantage of new tools for manipulating neuronal neuronal now taking advantage of new tools for manipulating are Researchers depth how activity within specific in more activity in animal models to explore compulsive behaviors. In might trigger or prevent connections within CSTC circuits hyperactivity simulated a type of cortico-striatal one set of experiments, researchers that r that has been observed in the brains of patients, and found What’s Next Next What’s The animals’ OCD-like behavior grooming. over several days caused mice to increase with SSRI treatment. persisted for weeks and could be reversed ƒ ƒ ƒ functional abnormalities in CTSC circuits. Emerging Research 30 49 reduce the reduce What’s 44 45 These molecules 42 47 When the SLC1A1 gene 51 53 43 Glutamate signaling has been further implicated Imaging studies have also found evidence of high Imaging studies have also found 50 48 Different dopamine receptors are predominant in the predominant receptors are dopamine Different 46 Other genetic changes that alter glutamate signaling in the 52 is switched off in a mouse model of OCD, OCD-like symptoms such as excessive is switched off in a mouse model of OCD, OCD-like symptoms reduced. are grooming intensity of obsessions and compulsions when combined with SSRIs. intensity of obsessions and compulsions more, medications that activate dopamine receptors can provoke side effects that can provoke medications that activate dopamine receptors more, mimic symptoms of OCD. are found at high levels within certain regions of the basal ganglia, implicating of the basal ganglia, regions at high levels within certain found are function. circuit in CSTC serotonin levels of glutamate and related compounds in the brains of patients with OCD, compounds in the levels of glutamate and related excitatory and inhibitory (direct and indirect) pathways between the thalamus and pathways between and indirect) excitatory and inhibitory (direct signaling may be critical for balancing signaling the cortex, suggesting dopamine between the two pathways. information flow and regulating and demonstrate that these levels change when patients undergo and respond to and respond change when patients undergo and demonstrate that these levels cognitive behavioral therapy. brains of mice can provoke OCD-like symptoms. brains of mice can provoke in OCD through genetic studies, which have linked the disorder to variations in genetic studies, which have linked the disorder in OCD through SLC1A1, a gene that encodes a glutamate transporter. Glutamate is the most abundant excitatory neurotransmitter in the brain, and excitatory neurotransmitter Glutamate is the most abundant to have found with OCD were Individuals circuits. for CSTC the driving force fluid, the fluid that bathes the cerebrospinal higher levels of glutamate in their brain, than healthy controls. Evidence of a role for dopamine signaling comes from clinical studies that found dopamine signaling comes from for Evidence of a role that block dopamine signaling that certain antipsychotic medications Because treatment with SSRI medications successfully reduces symptoms for many medications successfully reduces with SSRI Because treatment been assumed to play an system has the brain’s serotonin patients with OCD, certain serotonin studies have suggested that Genetic in the disorder. important role in people with OCD. altered and transporters may be receptors Studies continue to increase the understanding of the role of glutamate in OCD. the understanding of the role Studies continue to increase What’s Next What’s ƒ ƒ Recent findings What We Know We What ƒ NEUROTRANSMITTERS Emerging Research 31 although 59 62 Studies investigating genes 60 , which encodes a glutamate GRIN2B 61 63 55, 56, 57 gene, which encodes a glutamate transporter, gene, which encodes a glutamate SLC1A1 Some studies have also examined the heritability of OCD traits independent of OCD traits independent also examined the heritability Some studies have 58 54 findings were inconsistent, albeit promising. findings were Two genome-wide association studies have compared the DNA sequences of people the DNA genome-wide association studies have compared Two and their of variants that associate with the disorder, with and without OCD in search mutations associated with the disorder that are not inherited—found mutations in that are mutations associated with the disorder genes involved in developmental and immunological pathways. A small study that compared all of the protein-coding genes in 20 children with children genes in 20 all of the protein-coding small study that compared A strategy aimed at identifying rare OCD to the genes of their unaffected parents—a encoding serotonin receptors and transporters and dopamine receptors have also transporters and dopamine receptors and receptors encoding serotonin found some positive associations with OCD. Another gene implicated in multiple studies is Another gene implicated in multiple subunit that is important for synaptic plasticity. receptor variations in this gene were not linked to OCD in genome-wide association studies. variations in this gene were to be associated with OCD. These studies have largely focused on genes associated focused studies have largely to be associated with OCD. These have found an glutamate, and dopamine signaling. Several such studies with serotonin, association with the Recent findings hypothesized for associations among sets of genes Several genetic studies have searched disorder. definitive associations with OCD. Variations in numerous genes have been linked genes have been Variations in numerous OCD. definitive associations with is insufficient evidence to of support, but so far there to OCD with varying degrees of genes as a definitive risk factor for the implicate any single gene or combination This heterogeneity may be part of the reason that genetic studies have yielded few that genetic may be part of the reason This heterogeneity traits, and suggest that different types of OCD thoughts and behaviors (such as thoughts and behaviors (such types of OCD that different traits, and suggest but may have overlapping hoarding) and thoughts, ordering, cleaning, forbidden and biological origins. distinct genetic studies. genetics in influencing these role of a These studies confirm of an OCD diagnosis. What We Know We What twin and family established through genetics in OCD has been well for role A GENETICS Emerging Research 32

64 e 66 68 65 A similar study also found elevated levels of proinflammatory molecules of proinflammatory similar study also found elevated levels A 67 in unmedicated adults with OCD. Another study examined blood samples from pediatric patients with OCD and samples from Another study examined blood to healthy cells and markers compared found elevated levels of proinflammatory controls. Using positron emission tomography (PET) imaging, researchers found evidence found (PET) imaging, researchers emission tomography Using positron OCD had higher levels of inflammation within the that unmedicated adults with than healthy controls. that comprise CSTC circuits brain regions Recent studies suggest that anti-inflammatory or other immune-modulating Recent studies suggest that anti-inflammatory or other immune-modulating may be beneficial for people with OCD. treatments What’s Next What’s ƒ These cases have led researchers to investigate the role of inflammation in cases of to investigate the role These cases have led researchers associated with infection. not clearly OCD that are ƒ Recent findings Recently, the immune system has drawn the attention of researchers interested interested of researchers system has drawn the attention the immune Recently, lead to a rapid onset of obsessive compulsive in OCD. Certain infections can The best studied example is pediatric autoimmune behavior in some individuals. which infections (PANDAS), associated with streptococcal disorders neuropsychiatric overactive immune system triggering inflammation in is thought to be caused by an the brain’s basal ganglia. IMMUNOLOGY Know We What likely be of small effect individually, much larger studies may be needed to find them. studies may be needed much larger effect individually, likely be of small Since the biological origins of OCD remain largely unknown, the genetic factors genetic factors unknown, the largely of OCD remain biological origins Since the been considered beyond those that have so far may lie the disorder associated with OCD ar factors that contribute to In addition, because the genetic candidate genes. What’s Next Next What’s Emerging Research 33 77 75 eatments when essant effects, and in 71, 72 70 have shown positive effects. 73, 74 SSRIs directly affect serotonin, a neurotransmitter in the brain. An SRI in the brain. a neurotransmitter serotonin, affect SSRIs directly 69 Although ketamine may be unsuitable for widespread use due to its Although ketamine may be unsuitable for widespread 76 When combined with CBT, a single dose of ketamine reduced OCD symptoms a single dose of ketamine reduced When combined with CBT, for weeks. undesirable side effects and potential for abuse, researchers are exploring related exploring are researchers undesirable side effects and potential for abuse, for OCD. glutamate-modulating molecules as potential fast-acting treatments Rapastinel, an alternative medication to ketamine that targets NMDA receptors NMDA Rapastinel, an alternative medication to ketamine that targets and of OCD, anxiety, symptoms in the brain, in a small pilot study decreased ketamine. with associated effects side the causing without hours within depression Riluzole, which is currently used to treat ALS, and the anti-convulsant drugs used to treat Riluzole, which is currently lamotrigine and topiramate that has long been used glutamate-modulating drug Ketamine is an FDA-approved as an anesthetic. It has been found to have fast-acting antidepr Memantine, a drug approved for the treatment of Alzheimer’s of for the treatment approved disease, has been Memantine, a drug to have a positive effect on OCD tr found in small randomized trials added to standard medications. added to standard with OCD symptoms. obsessions in patients rapidly reduced a small trial the drug fluoxetine (brand name Prozac); and fluvoxamine (brand name Luvox); (brand name Paxil). paroxetine sertraline (brand name Zoloft); known as Anafranil has been available the longest, and is the best studied medicine available the longest, and Anafranil has been known as for OCD. approved been FDA for OCD. Four SSRIs have ƒ ƒ ƒ ƒ Researchers have been studying alternative medications to SSRIs, with much of the have been studying Researchers in that modulate glutamate signaling on treatments developments focusing current for treating FDA-approved have been drugs the brain. Several glutamate-modulating under clinical evaluation in OCD. other conditions are Recent findings ƒ ƒ ƒ ƒ Serotonin reuptake inhibitors (SRIs) and selective serotonin reuptake inhibitors reuptake (SRIs) and selective serotonin inhibitors reuptake Serotonin effective in and have been proven in all of psychiatry, commonly used (SSRIs) are OCD. treating DRUG DEVELOPMENT DRUG Know We What TREATMENT Emerging Research 34 ous conditions, 79, 80 er studies would er studies would Larg 78 Researchers posit that early intervention with Researchers 82 for treating patients in just four days. Of the 1,200 people for treating 81 CBT in OCD might have a similar effect. who have gone through the treatment, 70 percent remain in remission four years in remission remain 70 percent the treatment, who have gone through later. Using CBT to prevent the onset of symptoms: A study has shown that treating study has shown A onset of symptoms: the Using CBT to prevent anxiety symptoms with CBT can prevent of mothers with anxiety disorders children occurring in those children. from Intensive CBT treatment: Studies have shown that several days of intensive CBT Studies have shown that several days of intensive Intensive CBT treatment: recently made A study out of Norway can have a long-term effect. treatment popular news headlines Looking forward, studies on the effects of CBT in the brain are ongoing. Imaging ongoing. studies on the effects of CBT in the brain are Looking forward, which can help to CBT, how the brain reacts being used to predict studies are of CBT and medications. to which combinations which people will respond predict its impact on the brain in looking at glutamate and are researchers In particular, studies. both have related and UCLA Stanford combination with CBT. ƒ ƒ Recent findings relating to intensive CBT treatment and the use of CBT to prevent the of CBT to prevent and the use relating to intensive CBT treatment Recent findings onset of symptoms show promise. CBT includes a structured approach towards increasing an individual’s awareness awareness an individual’s increasing towards approach CBT includes a structured this, he or she can view negative thinking. Through of his or her own inaccurate or and learn effective manner, in a more respond clearly, challenging situations more CBT focuses on solutions and rests life situations. how to better manage stressful The individual works influence behavior. perceptions on the idea that thoughts and (therapist or psychotherapist) in a limited number of with a mental health counselor addition effectively online, in indicates that CBT can be delivered sessions. Research shows that CBT can benefit numer to face-to-face sessions. Evidence Cognitive Behavioral Therapy (CBT) (CBT) Therapy Behavioral Cognitive PSYCHOTHERAPY PSYCHOTHERAPY for OCD. The medication(s), is a first-line treatment with paired Psychotherapy, to related research and emerging details psychotherapy treatments following section therapies. and emerging commonly used including anxiety disorders, PTSD, eating disorders, and others. PTSD, eating disorders, including anxiety disorders, n small, single studies single studies in small, some promise that have shown medications Additional and caffeine, opiates such as morphine such as amphetamine and include stimulants nausea. used to treat a drug ondansetron, and buprenorphine, What’s Next What’s be needed for more conclusive results. results. conclusive be needed for more Emerging Research 35

85 oup, 86 ol gr In fact, ERP has In fact, ERP 84 In addition, a University of 87 Experts believe ACT may help patients help may ACT believe Experts 89

83 88 There is a commonly held belief that ERP drop-out rates are quite high at 25 percent. quite high at 25 percent. rates are drop-out held belief that ERP is a commonly There found it to be untrue. this belief and actually One study examined Pennsylvania study found that family-based CBT was more effective than other types family-based CBT was more Pennsylvania study found that of CBT for young children. Family members may play an important role in an individual’s OCD and are often in an individual’s OCD and are important role Family members may play an are this, there address behaviors. To and related involved in a patient’s rituals For a family members in behavioral treatments. strategies that involve numerous homework (as part may act as a coach during exposure child, for example, a parent which treatment, Another option is the multifamily behavioral treatment). of ERP behavioral therapy. and family-assisted groups combines elements of family support Family Therapy Family relatively low drop-out rates that are on par with drop-out rates for other mental on par with drop-out rates that are low drop-out relatively disorders. In terms of recent findings, family therapy has been shown to have a positive effect on effect positive a have to shown been has therapy family findings, recent of terms In can help parents that participation in family treatment family members. Studies show study in this approach, engaged in a recent UCLA deal with their own anxiety. found treatment to be slightly effective. to be found treatment ACT is an intervention that uses acceptance and mindfulness strategies, together ACT is an intervention that uses acceptance and mindfulness accept what is out with commitment and behavior change strategies, to help patients lives. The and enrich their and commit to actions that can improve of their control acceptance, cognitive defusion, being present, processes: intervention uses six core action. committed and values, context, as self Acceptance & Commitment Therapy (ACT) (ACT) Therapy & Commitment Acceptance and Yale in 2012 developed a “Family Accommodation Scale for OCD” to measure Scale for OCD” to measure Accommodation in 2012 developed a “Family Yale and on OCD behaviors. of family members impact/role ERP is a type of CBT, and the one most commonly used to treat OCD. Through this OCD. Through treat used to one most commonly and the a type of CBT, is ERP objects and situations exposed to the thoughts, images, are individuals treatment, individuals prevention, response or initiate obsessions. Through that lead to anxiety anxiety or compulsive behavior once the to learn to not enact a work with a therapist been triggered. obsessions have Exposure Response Prevention Therapy (ERP) (ERP) Therapy Prevention Response Exposure get into and remain compliant with ERP treatment, and ACT was recently found to be ACT was recently and treatment, compliant with ERP get into and remain ACT recent Utah State University study investigated how A an effective intervention. using a contr activates the brain for both obsessions and perfectionism, and, Emerging Research 36 -based eatment has ds threats: they ds threats:

92 While potentially promising, inhibitory learning requires inhibitory learning requires While potentially promising, 91 Further testing is required for more conclusive results. for more Further testing is required 93 Traditional ERP uses an extinction model that helps people break the the that helps people break uses an extinction model ERP Traditional 90 ended. with ongoing in-person treatment, rather than as a replacement. The programs enable The programs a replacement. rather than as with ongoing in-person treatment, or after tr users to practice CBT skills on their own in between sessions, therapy. Studies have found that software programs using CBT principles can be using CBT principles can be programs Studies have found that software therapy. must be used in conjunction these programs OCD. For many, effective in treating software programs. One advantage to these therapies is that apps and computer One advantage to these therapies is that programs. software lower cost alternatives to traditional and provide widely accessible are programs New technologies are on the rise for mobile OCD treatment options. These include on the rise for mobile OCD treatment New technologies are and computer smartphone-based applications (“apps”), as well as internet place at UCLA in 2013. place at UCLA Technology by Powered Therapy teaching them to respond rather than avoid. teaching them to respond for youth with clinical anxiety (not OCD specific) took treatment ABM study of A reacts by pressing a button left or right subconsciously. The patient can be trained to left or right subconsciously. a button by pressing reacts bias, the threat correct image, which can to the anxiety-provoking always respond tends to be multi-session and can be delivered by computer. For example, a by computer. can be delivered tends to be multi-session and so that a patient rapidly, image on a screen an could present computerized program see the world as more threatening and frequently sense danger in their environment. sense danger in their environment. and frequently threatening see the world as more This treatment threat. this bias towards by reducing anxiety ABM aims to reduce Attention Bias Modification (ABM) Bias Modification Attention anxious individuals have a bias towar ABM is based on the view that Johns Hopkins and Baylor. conclusive results. clinical trial for more empiral testing in OCD in a controlled The use of an inhibitory learning approach with CBT was found to benefit youth with with CBT was approach The use of an inhibitory learning several sites, including UCLA, to a 2016 study conducted across OCD, according model, people learn to take the fear away from the obsession, which potentially the obsession, which learn to take the fear away from model, people last longer. makes its effects link between an obsession and a compulsion in order to make the compulsion go to make the in order obsession and a compulsion link between an back. In the inhibitory learning the compulsion may come over time, However, away. something is “safe” in such a way that is strong enough to block out (“inhibit”) the enough to in such a way that is strong something is “safe” original fear. Inhibitory learning is an approach to ERP treatment that helps maximize the maximize that helps treatment ERP to approach learning is an Inhibitory (or reduces and optimize how ERP model is a way to understand This treatment. people learn that needs to help be effective, ERP To obsessional fear. “extinguishes”) Inhibitory Learning Inhibitory Emerging Research 37 The 95 94 TMS is a noninvasive procedure that uses magnetic fields TMS is a noninvasive procedure 96 A deep transcranial magnetic stimulation (TMS) device was approved by the FDA by the FDA deep transcranial magnetic stimulation (TMS) device was approved A in 2018 for use in OCD. study on pp. 38-39). Magnetic Stimulation Transcranial DBS in OCD is currently being studied with NIMH Brain Initiative funding by Wayne being studied with NIMH Brain Initiative funding by Wayne DBS in OCD is currently (see case Goodman at Baylor University and Darin Dougherty at MGH/McLean more precise stimulation that is only in response to brain activity related to identified related to brain activity that is only in response stimulation precise more continuous stimulation. Closed-loop biomarkers, as opposed to DBS which provides A recent comparison of 25 studies involving deep brain stimulation for OCD found comparison of 25 studies involving deep brain recent A targets. anatomical response rates between five different in little difference much which provides will involve closed-loop DBS, next generation of DBS research been targeted. been targeted. DBS, in which electrodes are implanted in the brain to stimulate targeted areas, is an areas, targeted implanted in the brain to stimulate are DBS, in which electrodes OCD. The number of patients who for treatment-resistant treatment FDA-approved regions of the brain have different deep brain stimulation is small, and have received Deep Brain Stimulation Deep Brain magnetic stimulation (TMS), have shown some efficacy in treating patients whose shown some efficacy in magnetic stimulation (TMS), have to medication or psychotherapy. respond OCD symptoms do not adequately BRAIN STIMULATION deep brain stimulation (DBS) and transcranial Brain stimulation therapies, including to be large-scale scientific studies on the long-term impacts of app usage among scientific studies on the long-term impacts to be large-scale needed. studies are individuals with OCD. Further therapists, and hopes to obtain FDA approval. The project received an initial grant received The project approval. hopes to obtain FDA therapists, and have yet there new, still relatively are 2018. Since apps for OCD of $725,000 in early (MGH) was developing a smartphone CBT therapy app with an emphasis on app with an emphasis a smartphone CBT therapy (MGH) was developing to live first app that connects users MGH seeks to develop the inhibitory learning. customizable treatment plans. customizable treatment Hospital at Massachusetts General Sabine Wilhelm of this writing, Dr. As of the time in 2014) and received $1 million in venture seed funding in early 2018. The app in early 2018. seed funding in venture $1 million and received in 2014) therapy “guidance,” and ERP access to educational material, and includes is free Apps are primarily developed by private companies. NOCD, a smartphone-based NOCD, a smartphone-based companies. by private developed primarily Apps are (founded startup by a Chicago-based OCD, was developed those with tool to help Emerging Research 38

97 Experts 99 geting deeper geting deeper To date, approximately 20 locations across the across 20 locations date, approximately To 98 Dr. Wayne Goodman, MD, Chair of the Menninger Department of Wayne Dr. Psychiatry and Behavioral Sciences at Baylor College of Medicine, grant in 2018. a $1.5 million received prestigious three received and his colleagues recently Goodman Dr. NIH BRAIN Initiative to develop next generation the grants from systems, available “closed loop” DBS devices. Unlike currently the brain local field potentials (LFPs) from these devices can record will allow scientists as well as deliver stimulation. This feature the disease and to further refine about and clinicians to learn more ƒ CASE STUDY CASE NIH’S THE BRAIN INITIATIVE—NEUROSTIMULATION Health (NIH) funds “The Brain The U.S. National Institutes of (BRAIN) Advancing Innovative Neurotechnologies through Research our understanding of the human Initiative,” aimed at revolutionizing researchers OCD this initiative, two prominent brain. Through next have grants to study closed-loop deep brain stimulation—the DBS treatment: precise generation of more Recently, a meta-analysis of 15 studies found the therapy to be more effective at therapy to be more of 15 studies found the a meta-analysis Recently, placebo. patients than a OCD symptoms in treatment-resistant reducing country have access to the FDA-approved TMS device, though experts anticipate it device, though experts anticipate TMS to the FDA-approved country have access next few years. available over the readily will become more to stimulate nerve cells in particular regions of the brain for treatment of OCD. treatment the brain for of regions in particular nerve cells to stimulate report that the next area of research for TMS is to develop new coils, which deliver for TMS is to develop new coils, of research that the next area report Transcranial precise. in the brain to make it more targets and to identify the current, via delivered current direct stimulation, which uses constant, low current direct and, through for use in depression on the head, has shown some promise electrodes addition, low-intensity focused may also be useful in OCD. In further research, than in the brain circuits specific in targeting be more ultrasound has the potential to TMS. is possible through Transcranial magnetic stimulation is currently used to target superficial parts of the superficial used to target is currently stimulation magnetic Transcranial tar its potential for is evaluating clinical trial an ongoing brain, though in patients with OCD. structures Emerging Research 39 cuit- and adjust treatment. This technology is expected to lead to the is expected to This technology treatment. and adjust machine learning to a “smart device” informed by development of to the patient’s clinical stimulation according automatically adjust such a device In addition, brain recordings. direct state based on a dynamic disease so to monitor the fluctuations in might be used symptoms before can be automatically adjusted that DBS stimulation in partnership with Goodman is working Dr. become unmanageable. all Meeting study. for this device manufacturer, a medical Medtronic, DBS system in a prototype-adaptive would result study milestones in OCD symptoms and device- that would manage fluctuations side effects automatically. related Dr. Darin Dougherty, MD, MMSc, Psychiatrist, McLean OCD Darin Dougherty, Dr. at Division of Neurotherapeutics of the Institute and Director in 2016. a $625,000 grant received Massachusetts General Hospital, and will develop DBS for OCD, this project In an effort to improve study a next-generation, brain cir test in a small early feasibility oriented DBS treatment for drug-refractory OCD. The main objective for drug-refractory oriented DBS treatment the deep brain and the cortex (brain is to test a stimulator that affects It the abnormal CSTC synchrony. surface) at once and tries to break them keeping frequencies, at slightly different drives two brain areas is to test whether activity in the out of sync. The second objective proven to the symptoms of OCD. No study has CSTC loop correlates record difficult to linked in humans because it is that these two are the human brain, especially over long periods of time and from the The study will use a novel technology, deep brain areas. from the brain’s activity while PC+S “sensing DBS,” to record Medtronic This study leverages a broad delivering the stimulation treatment. team of psychiatrists, statisticians, a neurosurgeon, interdisciplinary all with experience in OCD and brain and electrophysiologists, stimulation. ƒ Moving the Field Forward 40

Focusing on early recognition and prevention. Focusing on early recognition Instituting better and more training on effective treatments for clinicians. treatments training on effective Instituting better and more delivery (e.g., telehealth, computer- Leveraging alternative models for treatment based or app-based delivery). ƒ ƒ ƒ The most promising approaches for increasing access to care include: access to care for increasing approaches The most promising Because current treatments are effective and would be effective for more people effective and would be effective for more are treatments Because current that an of the experts interviewed recommend than half if they had access, more This would help the people into treatment. immediate goal should be to get more people toward of people in the short term, moving many more number broadest living fully functional lives. BETTER DISSEMINATE CURRENT TREATMENTS AND INCREASE INCREASE AND CURRENT TREATMENTS BETTER DISSEMINATE CARE TO ACCESS SHORT-TERM APPROACH SHORT-TERM With this definition in mind, experts have varying opinions on the most promising opinions on the most promising this definition in mind, experts have varying With will vary depending They note that approaches avenues for advancing the field. as outlined time frame for results, and the desired on the level of funding available support all three of the experts interviewed noted the need to About one-third below. strategies. Most experts agree the ultimate goal of OCD research is to support more people to people to is to support more ultimate goal of OCD research the Most experts agree symptoms. Given the complexity to no disruptive live functional lives with minimal do experts people differently, and what is known about how it affects of the disorder expectation. altogether is a reasonable not believe eradication of OCD these approaches, including short-, medium- and long-term opportunities. and long-term opportunities. including short-, medium- these approaches, Analysis of the history and current state of the OCD research field along with expert field along with expert of the OCD research state history and current Analysis of the to help the a number of approaches and clinicians surfaced researchers input from The following section outlines effectively. people, more more treat field eventually FIELD FORWARD FIELD PART FOUR: MOVING THE MOVING FOUR: PART Moving the Field Forward 41 improving neuromodulation (DBS and TMS) and developing new noninvasive neuromodulation improving ways to stimulate the brain; and and psychotherapy to develop of neurobiology combining the understanding with psychotherapy). (e.g., combining brain stimulation treatments precise more studying predictors and how people respond to treatments (e.g., understanding to treatments and how people respond studying predictors brain scans, will work for which patients based on symptoms, what treatments between research translational strong require and other factors); this would clinics, labs, and imaging experts; y y y y y y Develop new psychotherapy treatments. not recommend Discover new medications for use in OCD. Most experts do uses for existing new medications, but discovering new developing entirely medications that might be useful for OCD. Develop a precision medicine approach (note: there was the most consensus about was the (note: there medicine approach Develop a precision by: this approach) Increasing advocacy and lobbying to demand more government investment in to demand more advocacy and lobbying Increasing research. OCD-related Building advocacy and awareness to reduce stigma and address the hidden nature of the of nature the hidden and address stigma to reduce awareness advocacy and Building disorder. The longest-term approach to move the field significantly forward is to make new to move the field significantly forward The longest-term approach of About one-third discoveries about the biology and physiology of the disorder. critical to advancing the experts interviewed believe basic science discoveries are from making significant field. Experts estimate the field is ten to twenty years away LONG-TERM APPROACH LONG-TERM OF THE DISORDER THROUGH THE CAUSES UNDERSTAND SCIENCE RESEARCH BASIC ƒ ƒ ƒ The most promising approaches are noted below. are approaches The most promising Thirty to fifty percent of people with OCD do not respond to current treatments. Half treatments. respond to current do not of people with OCD percent Thirty to fifty to moving approach that a good medium-term of the experts interviewed recommend to reach develop new treatments living fully functional lives is to people toward more offerings. to current those who do not respond MEDIUM-TERM APPROACH MEDIUM-TERM PEOPLE AND TREAT DIAGNOSE TO WAYS FIND BETTER ƒ ƒ Moving the Field Forward 42 neuroimaging studies; neuroimaging and studies; neuromodulation may be and cell types that circuits studies to understand the post-mortem brain into has yielded enormous insight with OCD. Such research abnormal in people it is a and and schizophrenia), syndrome Tourette pathology in other fields (e.g., needs to fill. glaring gap that the OCD field animal models; While some experts believe discoveries in basic science will move the field the While some experts believe discoveries Experts note that basic science research several cautions. furthest ahead, they provide some and live with the disorder, who currently will have the least effect on people that would be research through bullet” to be discovered is no “silver believe there and applicable in relevant keep the research applicable to every case of OCD. To should incorporate clinical they believe any basic science research the nearer-term, perspectives. ƒ the suite of genes would include gaining an understanding of The genetics approach it has an inflection point where The genetics field is at implicated in the disorder. or alteration, but rather that OCD is not caused by a single gene mutation discovered development. Now the field to influence brain circuit many genes working together sizes to identify the sample genetic studies with large needs to conduct large-scale of OCD in understanding the genetics Breakthroughs suite of genes responsible. models for conducting further studies. perfect animal could lead to developing more ƒ ƒ ƒ In terms of neuroscience, the goal is to understand the circuit level functioning of the level goal is to understand the circuit the In terms of neuroscience, through: disorder breakthroughs in understanding the causes of OCD, with the most promising promising with the most of OCD, the causes in understanding breakthroughs genetics research. degree, and to a lesser neuroscience, being in approaches Recommendations for Philanthropy 43

. Sustained funding would benefit the field by:

Allowing researchers to think bigger, more creatively, and longer-term. and longer-term. creatively, more think bigger, to Allowing researchers feel constrained by available dollars and funding currently Many researchers priorities and practices of NIMH. Connect stakeholders (researchers, funders, advocates) with adjacent interests funders, advocates) with adjacent interests Connect stakeholders (researchers, OCD. to efforts in other psychiatric disorders) (e.g., brain research, grant to grant. from feel to chase funding researchers Alleviating the pressure Connect researchers within disciplines by encouraging and requiring data requiring within disciplines by encouraging and Connect researchers sharing. dissemination. findings to clinical practice through Help connect research sample sizes. multiple sites to increase across efforts Connect research Connect researchers across disciplines. across Connect researchers y y y y y y y y y y y y y y

Sustainer . In order to connect stakeholders throughout the field, philanthropic actors can: the field, philanthropic to connect stakeholders throughout Connector. In order ƒ ƒ Philanthropy can play a unique role in the OCD research field going forward, field going forward, in the OCD research can play a unique role Philanthropy noted the investment, experts increased to date. With especially given its modest role as best suited for philanthropy. following roles ROLES PHILANTHROPIC OPPORTUNITIES PHILANTHROPIC

FOR PHILANTHROPY most can resources insight on how philanthropic provides The following section funding Since mental health research. the trajectory of OCD significantly influence slow for OCD is limited and often specifically earmarked government sources from on the field of OCD can have significant impact philanthropy bureaucratic, and as catalyst, can serve the role Philanthropy funding source. as a nimble, adaptive new relationships opportunities to forge and can create and instigator, convener, funders and policymakers. While this academic institutions, among researchers, donors transformational gifts to catalyze change, individual to large, section relates the kinds of activities that, with understanding it with an eye toward can also read and forward would support the field’s growth dollars, additional philanthropic trajectory. PART FIVE: RECOMMENDATIONS RECOMMENDATIONS FIVE: PART Recommendations for Philanthropy 44 NIMH has never issued an RFP related to OCD research. With more public and more With to OCD research. related issued an RFP NIMH has never it might be inclined to do so. pressure, Congressional funders who support related OCD, around awareness increased With to could be inspired disorders, or other related causes such as brain research OCD field. the contribute toward Promoting collaboration across sites and disciplines. across collaboration Promoting Encouraging new researchers to enter the field. new researchers Encouraging for funding. competition Reducing y y y y y y y y y y . An influential funder in the OCD field could serve as a catalyst, attracting funder in the OCD field could An influential Catalyst. New funding could and other sources. government from additional funding grants, and an government to larger that could lead research support innovative and awareness, around advocacy voice could enhance efforts influential funder For example: allocations for OCD. government-spending which could increase The majority of experts emphasized the tremendous opportunity and potential opportunity The majority of experts emphasized the tremendous could make by helping the field develop better treatments impact that philanthropists include supporting the following categories. recommendations for OCD. Specific Translational Research and Treatment Development and Treatment Research Translational There are mixed opinions on whether basic research is best left to government funding is best left to government basic research mixed opinions on whether are There About one- philanthropy. for additional funding from whether it is a good target or and as a is underfunded generally, believe basic research interviewed experts of third to better understand the brain investment in research philanthropic long-term approach, experts of OCD could move the field ahead. In genetics specifically, and genetics circuitry and a few million dollars could researchers note the field is underpopulated with good in basic and animal modelmake a big impact. Others caution against investing heavily also NIH, and NIMH. This group well-funded by NSF, believing it is currently research, the field across slow and unproductive has been incredibly basic research that believes that make it into the lives of people leading to very few breakthroughs of psychiatry, with OCD. Basic Research STRATEGIES might use to move the several strategies that philanthropists Experts recommend dollars philanthropic Experts have varying opinions about where field forward. approach impact, and many advocate for a multi-pronged would have the greatest below. outlined that covers all the areas ƒ Recommendations for Philanthropy 45 H funds very limited psychosocial research or treatment studies. or treatment psychosocial research H funds very limited Lobbying Congress to allocate dedicated funding toward OCD research, which has OCD research, to allocate dedicated funding toward Lobbying Congress experts Several AIDS. and cancer, breast autism, as such fields other for successful been for the field, since government basic research note this is the best way to approach far vaster than those of philanthropy. coffers are Partnering with institutions such as IOCDF and Peace of Mind Foundation to help Partnering with institutions such stigma, This could lead to reduced public understanding of OCD. support greater and accurate diagnoses. frequent more better community support, and Phase 2 proof of concept studies for potential new drugs to treat OCD. Pharmaceutical to treat new drugs of concept studies for potential Phase 2 proof but philanthropy approval, to FDA Phase 3 trials, the precursor companies conduct Phase 2 trials. through drugs in discovering new uses for existing could play a role Research to better connect what is happening in the brain to enhance therapy. Experts the brain to enhance therapy. connect what is happening in to better Research industry would where not an area since it is niche for philanthropy note this is a good in not already companies are pharmaceutical and device capital (as be likely to provide NIM this space), and Translational research that fills the gap between basic science and clinical practice. This and clinical practice. basic science gap between that fills the research Translational medicine approach. personalized and a precision move toward the field could help Below are several funding approaches illustrated by case studies featuring philanthropic illustrated by case studies featuring philanthropic several funding approaches Below are and medicine. entities working to make transformational discoveries in science PHILANTHROPIC APPROACHES Across all of the above strategies, experts recommend facilitating collaboration in the experts recommend all of the above strategies, Across data sharing, supporting multi-disciplinary teams (e.g., including the field through multiple sites. clinical perspective), and investing across ƒ ƒ Philanthropic investments in advocacy and awareness can help build the field in terms awareness investments in advocacy and Philanthropic of talent entering the potential government investment, and pipeline of public interest, recommend: field. Experts Advocacy and Awareness Advocacy Some experts believe supporting treatment dissemination will produce the largest return return the largest will produce dissemination treatment Some experts believe supporting supporting include for philanthropy Potential roles on investment for philanthropy. such as telehealth or mobile delivery mechanisms, the development of novel treatment trained to deliver treatment the supply and quality of providers apps, and increasing appropriately. Treatment Dissemination Treatment ƒ ƒ ƒ Recommendations for Philanthropy 46 opical 100 grantees to track progress grantees to track progress increase collaboration increase Partner with government, local and international NGOs, academic institutions, pharmaceutical companies, funders, and private sector leaders Fast-track deployment of new tools and technology that NTDs treat ending NTDs towards efforts Lead advocacy and awareness Conduct ongoing monitoring & evaluation of investees and Fundraise and distribute grants to aligned non-profits Fundraise and distribute grants a portfolio of high-impact Raise and allocate capital; manage and reaching treatment investments that work on scaling disease elimination goals donors and to coordinate efforts Serves as a platform across Awareness Monitoring & Evaluation Technology Advocacy & Platform Outreach Grantmaking Investment years, the fund raised $118 million. years, the fund raised $118 The fund was created in 2012 by a private investment firm and its in 2012 by a private investment firm and The fund was created business, philanthropy, Additional funders across advisors. philanthropic and local communities have since joined government, medicine, education Within its first six dollars and expertise. the effort by contributing both diseases (NTDs) can live healthy and prosperous lives.” The Fund plans to and prosperous diseases (NTDs) can live healthy 2030. This is the only private philanthropic NTDs by end the most prevalent the most common neglected tr initiative solely dedicated to ending diseases. CASE STUDY CASE SEEKING TO DONOR COLLABORATIVE A THE END FUND: DISEASES TROPICAL NEGLECTED & ELIMINATE CONTROL people at risk of neglected tropical The End Fund’s goal is to “ensure one another’s resources, and join forces towards creating strategic partnerships. one another’s creating towards and join forces resources, When trying to address large-scale challenges, such as curing a mental health as curing a mental such challenges, large-scale to address When trying A parties. with other interested to join forces beneficial it can be greatly disorder, to pool funds, leverage collaborative enables funders like a donor formal structure DONOR COLLABORATIVES DONOR Recommendations for Philanthropy 47 . estimated budget to complete the study is $500 million, and initial estimated budget to complete the study is $500 million, and donors. funds came out of traditional operating dollars and private severe depression are connected to the university’s counseling system. are depression severe used to collect participant data. Smartphone apps are leading are and genetics researcher clinical researcher neuroscientist, A The holistically. depression to address which enables UCLA the study, As part of the study, UCLA students and staff fill out an online screen out an online screen students and staff fill UCLA As part of the study, symptoms that show depressive symptoms. Those of depressive Those and to be treated. the study, in have the opportunity to enroll and those with an online program, offered are with mild depression half by the year 2050, and to eliminate it by the end of the century half by the year 2050, and to eliminate depression on the largest embarked As part of the challenge, UCLA over ten years to 100,000 participants study in history: enrolling factors social and environmental identify genetic, biological, cognitive, associated with depression. In 2012, UCLA launched a series of “grand challenges,” which are are launched a series of “grand challenges,” which In 2012, UCLA that work projects research collaborative ambitious multi-disciplinary, Grand one goal. One of the challenges is the Depression towards in of depression to cut the burden Challenge, which has the goal CASE STUDY CASE DEPRESSION CHALLENGE UCLA across several sites to gather sufficient data. It could be beneficial to base a study at a could be beneficial to base to gather sufficient data. It several sites across alongside the data collection. to participants treatment and to provide university, BASED APPROACH BASED An sample sizes. is small research that a major challenge to OCD Experts agree study that would work large-scale this might be investing in a address to approach BIG BETS: LARGE SCALE, MULTI-DISCIPLINARY, UNIVERSITY- MULTI-DISCIPLINARY, SCALE, LARGE BIG BETS: Recommendations for Philanthropy 48 with potential of high clinical impact, with potential of high clinical

team research

translational years. over two to three $500,000 and provide Fellowships support young researchers to study early detection, Fellowships support young researchers $300,000 over two years. providing Young Innovator Team Awards support transdisciplinary and support Awards Innovator Team Young ƒ for people resources For its education initiative, the foundation provides a support groups, including educational resources, with lung cancer, options, and other resources. patient handbook to navigate treatment The foundation also supports the development of a patient-centric, at community that can be provided collaborative model of treatment live—access to the they hospitals to give all patients—no matter where most effective treatments. ƒ CASE STUDY CASE CANCER FOUNDATION BONNIE J. ADDARIO LUNG is a grantmaking Addario Lung Cancer Foundation The Bonnie J. in 2006 with the goal of turning public charity that was established ultimately and 2023, by disease managed chronically a into cancer lung than $30 has raised more eradicating the disease. The foundation activities. and related million for lung cancer research education, and treatment. Strategies include research, related the foundation supports clinical research In terms of research, biomarkers, small cell lung to early detection, diagnostic/prognostic and underlying causes of lung cancer in particular populations. cancer, Many experts advocate for an approach that accounts for short-term wins while investing that accounts for for an approach Many experts advocate and education, awareness supporting Several recommended in long-term breakthroughs. the bigger towards while working long-term in the short- and medium-terms, treatment in parallel. several portfolios grantmaking across be done through goals. This could MULTI-PRONGED GRANTMAKING THAT FOCUSES ON SHORT-, ON SHORT-, FOCUSES THAT GRANTMAKING MULTI-PRONGED OUTCOMES AND LONG-TERM MEDIUM-, Recommendations for Philanthropy 49 AMOUNTS INDIVIDUAL PRIZE INDIVIDUAL awarded: $30,840; $26,250; and awarded: $15,989 First Prize: $20,000 Second Prize: $5,000 $5,000 Award: People’s Choice First Prize: $100,000 Second Prize: $50,000 First Prize: $100,000 Second Prize: $80,000 winners were three Top CHALLENGE TOPIC Proof of Concept Phase” of Concept Proof Challenge to Crowdsourcing in Patient Enrollment Increase Oncology Trials Lung Cancer Early Detection Challenge: Concept to Clinic “Double Participation in Cancer Ideation Phase” Clinical Trials: “Double Participation in Cancer Implementation/ Clinical Trials: which includes factors such as solution design, innovation, which includes factors such as 101 PRIZE TOTAL AVAILABLE $100,000 $150,000 “Phase 2” $180,000 $30,000 “Phase 1” YEAR 2018 2016 2017 2015 The prizes are judged by a panel of experts using a points system. The The prizes are partners that specialize in foundation administers the prize through and DrivenData. managing competitions such as HeroX share of a $100,000-$180,000 prize. In 2016, the foundation published the of a $100,000-$180,000 prize. In 2016, the foundation share criteria matrix, impact, and cost. implementation plan, scalability, viability, Challenge History The Bonnie J. Addario Lung Cancer Foundation put out a global call toAddario Lung Cancer Foundation put out a The Bonnie J. to develop open source and researchers scientists, engineers, designers, into the clinic. machine learning that brings advances from software educational on age, country of origin, gender, no restrictions are There eligible for a and top contributors are accomplishment, etc. for eligibility, CASE STUDY CASE SCIENCE CHALLENGE DATA learning as a path towards discovering better therapeutics, and a prize might appeal better therapeutics, and discovering towards learning as a path the traditional sciences. and others outside of to engineers, designers, Given how few grants there are for OCD researchers, establishing a prize could establishing for OCD researchers, are grants there Given how few machine interviewees mentioned people to enter the field. Many incentivize new “PRIZE” APPROACH: COMPETITION TOWARDS BETTER BETTER TOWARDS COMPETITION APPROACH: “PRIZE” THERAPEUTICS Recommendations for Philanthropy 50 Pilot Awards: Early support for exploratory ideas, particularly those Awards: Pilot 2 years. up to $300,000 for up to with novel hypotheses; provides Support for high-priority topics in autism, with Awards: Research up to $1.3 Provides for conceptual novelty. a lower requirement million for up to 4 years Research Awards provide up to $1.3 million for up to 4 years up to $1.3 million for up to provide Awards Research for for high-priority topics in autism, with a lower requirement conceptual novelty. Pilot Awards provide up to $300,000 for up to 2 years as early up to $300,000 for up to provide Awards Pilot with support for high-risk, exploratory ideas, particularly those novel hypotheses. ƒ ƒ ƒ ƒ $78 million per year, a budget of approximately Funding to date: With supports over 250 investigators. Since its launch, it provided SFARI support to than $480 million in external research or committed more in the U.S. and abroad. than 480 investigators more SIMONS FOUNDATION York foundation based in New The Simons Foundation is a private in mathematics and basic science. The City that funds research & physical sciences, life sciences, foundation makes grants in math Autism Research Its research. and education & autism research, the understanding, has the mission of improving Initiative (SFARI) by funding disorders of autism spectrum diagnosis and treatment of the highest quality and relevance. innovative research within a strategy is to support diverse scientific disciplines SFARI’s genes to molecular framework that emphasizes connecting broader and to therapeutic to behavior, mechanisms, to neural circuits, to seed exploratory hypotheses, and interventions. The goals are substantial support for high-priority topics. to provide CASE STUDY CASE ƒ supports SFARI $78 million per year, a budget of approximately With or committed over 250 investigators. Since its launch, it has provided 480 than support to more external research than $480 million in more investigators in the U.S. and abroad. ƒ SIMONS FOUNDATION York foundation based in New The Simons Foundation is a private in mathematics and basic science. The City that funds research & physical sciences, life sciences, foundation makes grants in math Autism Research Its research. and education & autism research, the understanding, has the mission of improving Initiative (SFARI) by funding disorders of autism spectrum diagnosis and treatment of the highest quality and relevance. innovative research within a strategy is to support diverse scientific disciplines SFARI’s genes to molecular framework that emphasizes connecting broader and to therapeutic to behavior, mechanisms, to neural circuits, exploratory hypotheses, and to seed interventions. The goals are the substantial support for high-priority topics through to provide following awards: CASE STUDY CASE A key challenge of NIMH funding is that it is low-risk: a model often has to be proven often has to be proven is that it is low-risk: a model key challenge of NIMH funding A to scale up. often primarily used those funds are funds—and NIMH will award before ideas. innovative, early-stage, riskier gap when it comes to funding This leaves a key fill this gap in the field. and a foundation could philanthropy, for role This is a critical for other strategies foundations have used award two case studies that show Below are initiatives. health research mental and physical HIGH-RISK, HIGH REWARD GRANTMAKING WITH A FOCUS A FOCUS WITH GRANTMAKING REWARD HIGH HIGH-RISK, INNOVATION ON FUNDING Recommendations for Philanthropy 51 to promote cutting-edge and creative thinking about thinking cutting-edge and creative to promote

Synergy Awards: To encourage collaboration among health encourage collaboration To Awards: Synergy the study of disciplines to advance across from researchers or unconventional groundbreaking support IBD, these awards of a methodologies, whose risky outlook is justified by the possibility basic, translational, across awarded Grants are major breakthrough. $100,000 per investigator, provides and clinical science. This award up to a maximum of $300,000. Innovator Awards: To support new and veteran IBD researchers in veteran IBD researchers support new and To Awards: Innovator of basic, spanning the spectrum embracing novel, untested ideas up to $200,000 provide these awards translational and clinical science, two additional years. with potential to extend for for one year, ƒ IBD. In doing so, the foundation helps encourage new and seasonedIBD. In doing so, the foundation and test ideas. The foundation provides to push boundaries researchers Awards. and Synergy Awards Innovator this funding through ƒ around the world around THE KENNETH RAININ FOUNDATION THE KENNETH Rainin Oakland, California, the Kenneth family foundation based in A of life by championing is to enhance the quality Foundation’s mission research and supporting literacy, early childhood the arts, promoting at the heart and innovation are disease. Collaboration chronic to cure of all its programs. the prevention, seeks to improve The foundation’s health program of inflammatory bowel disease (IBD). Its diagnosis, and treatment innovative ideas and early support for high-risk, strategy is to provide an annual symposium that brings to facilitate collaboration through and clinicians from trainees researchers, together scientific leaders, CASE STUDY CASE Recommendations for Philanthropy 52 FIELD CONTRIBUTION Tool & Resource Development & Resource Tool Development & Career Training Strategic Achievements Strategic Portfolio Congruence Advancement Scientific Resource Building Resource ƒ ƒ Research Effectiveness Research ƒ ƒ ƒ Its assessment framework recommendations include include recommendations framework Its assessment 102 OPERATIONAL PERFORMANCE OPERATIONAL Global Research Knowledge Sharing Cooperative Research Strategic Partnerships Strategy Planning Milestones & Monitoring Management Financial Sustainability & Commercialization Transfer Technology Community Engagement How many annual presentations, publications, and citations have resulted from the from publications, and citations have resulted How many annual presentations, we have funded? research Can we quantify the scientific deliverables from the research we have sponsored? research the Can we quantify the scientific deliverables from the R&D pipeline? Is this faster or moving through What is the rate of projects have advanced, and how many slower than we anticipated? How many projects At what stage? have been terminated? What are our most important scientific milestones? Do outside experts consider our most important scientific milestones? Do What are these to be significant contributions to moving the field forward? Accountability ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ Collaboration ƒ ƒ ƒ ƒ Figure 2. Source: “Measuring and Improving Impact: A Toolkit for Nonprofit Funders of Medical Research.” Funders of Medical Research.” for Nonprofit Toolkit Impact: A and Improving “Measuring 2. Source: Figure Institute. Center of the Milken A FasterCures: Measuring progress in medical research can be complex. FasterCures, a center of FasterCures, can be complex. medical research in progress Measuring play in jump- can philanthropy role in the unique is interested the Milken Institute, a framework and development. It developed in medical research starting innovation based on effectiveness their organizational to assess and improve for foundations the field. best practices in MEASURING PROGRESS MEASURING The framework recommends a few key questions to guide in developing an The framework recommends advancement: understanding of a foundation’s contribution to scientific both internal measures of operational performance and external measures of the measures performance and external of operational both internal measures to the field. foundation’s contribution Recommendations for Philanthropy 53 ence for therapeutics designed to eliminate OCD symptoms, contact the Rodan Family therapeutics designed to eliminate Foundation at [email protected]. currently available treatments, access to treatments, support for those affected by support access to treatments, treatments, available currently OCD Foundation please contact the International programs, OCD and advocacy in the development of new in investing a funder interested If you are at iocdf.org. If you or your foundation are interested in learning more about OCD, including in learning more interested are If you or your foundation hundreds of thousands, if not millions, of people. By building on the findings and of people. By building on of thousands, if not millions, hundreds and examples, approaches, leveraging the cited strategies, and in progress, research in moving the field forward. play a key role can philanthropy There is enormous potential for philanthropy to influence the OCD field in a OCD field in influence the to for philanthropy potential is enormous There and make a meaningful differ over the next 10 to 20 years, significant way CONCLUSION Endnotes 54 .

https:// Indian , , accessed , last . https:// , (2016): https://www.

. , accessed October 2018, http://www.ocd2018.org/ der Foundation Genetics https://www.icocs.org/ . 37, no. 3 (2014): 319-335. Enigma-OCD International OCD Foundation der.” Molecular Psychiatry 18, no. der.” , accessed October 2018, 5th ed. (2013). . National Institute of Mental Health Current Treatment Options in Psychiatry 2, no. 3 Treatment Current National Institute of Mental Health National Institute of Mental , accessed October 2018, Spring 2009). ( . Yemmigannur Chandrashekhar Janardhan Reddy, Reddy, Chandrashekhar Janardhan Yemmigannur

. https://www.bbrfoundation.org/ . Liang, F.S. Goes, B. Maher, A.E. Pulver, Y.Y. Shugart, D. Y.Y. A.E. Pulver, Goes, B. Maher, . Liang, F.S. Arumugham, Dan J Stein, Albina Rodrigues Torres, Albina Rodrigues Torres, Dan J Stein, Arumugham, der (OCD).” der (OCD).” der (OCD),” . , no. 7 (2017): 977-995. ECNP Neuroscience Applied ECNP Neuroscience US National Library of Medicine National Institutes of Health Psychiatric Clinics of North America , 37, no. 3 (2014): 319-35. . . International OCD Foundation (2017). Diagnostic and Statistical Manual of Mental Disorders, Diagnostic and Statistical Current Neuropharmacology 15 Neuropharmacology Current 38, no. 5 (2016): 386-394. https://iocdf.org/expert-opinions/expert-opinion-glutamate/ . https://perma.cc/ZRG9-QMGB Psychiatric Clinics of North America https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918136/ Current Medicinal Chemistry Current

ecnp.eu/research-innovation/ECNP-networks.aspx 2018, August revised perma.cc/LHQ4-XFCC Genetics through Meta-analysis (ENIGMA) Consortium,” Genetics through October 2018, events/25th-annual-ocd-conference/custom-126-a9e0183a9fd94d4b8ec48aa1b62b9335.aspx studying involving 4,000-5,000 cases. Heidi A. Browne, Shannon L. Gair, Jeremiah M. Scharf, and Dorothy E. Grice. “Genetics M. Scharf, and Dorothy Jeremiah Shannon L. Gair, A. Browne, studying involving 4,000-5,000 cases. Heidi disorders.” and related of obsessive compulsive disorder http://enigma.ini.usc.edu/ongoing/enigma-ocd-working-group/ 7 (2013): 788-798. See also M. Mattheisen, J.F. Samuels, Y. Wang, B.D. Greenberg, A.J. Fyer, J.T. McCracken, D.A. Geller, D.L. D.L. D.A. Geller, McCracken, J.T. A.J. Fyer, B.D. Greenberg, Wang, Y. Samuels, 7 (2013): 788-798. See also M. Mattheisen, J.F. Askland, H.-D. Qin, N.C. McLaughlin, E.L. Nurmi, K.D. J.A. Knowles, M.A. Grados, M.A. Riddle, S.A. Rasmussen, Murphy, S.E. Stewart, K.-Y B.A. Cullen, J. Piacentini, D.L. Pauls, O.J. Bienvenu, the OCGAS,” from results association study in obsessive compulsive disorder: C. Lange, and G. Nestadt. “Genome-wide Valle, See also International Obsessive Compulsive Disor Molecular Psychiatry 20, no 3 (2015): 337-344. of obsessive architecture Association Studies. “Revealing the complex genetic Collaborative and OCD Collaborative Genetics using meta-analysis,” Molecular Psychiatry 23, no. 5 (2018): 1181-1188. compulsive disorder Obsessive compulsive Disorder,” disorders.” related Journal of Psychological Medicine of Glutamate. Can We Develop Treatments That Work Better and Faster?” That Work Develop Treatments of Glutamate. Can We accessed October 2018, (2015): 271-283. collaboration,” Comprehensive Psychiatry 76 (2017): 79-86. Psychiatry collaboration,” Comprehensive Research.” www.nimh.nih.gov/health/topics/obsessive compulsive-disorder-ocd/ www.nimh.nih.gov/health/topics/obsessive Matsunaga, Euripedes Constantino Miguel, Donatella Marazziti, Hisato Roseli Gedanke Shavitt, Shyam Sundar Maria Conceicao do Rosario, An international (OCD): compulsive disorder age of onset and suicidality in obsessive “Comorbidity, Viswasam. Kirupamani Lorrin M. Koran and Elias Aboujaoude. “Promising Treatments for Obsessive compulsive Disorder: A Call for Additional Call for A Disorder: for Obsessive compulsive Treatments Aboujaoude. “Promising Lorrin M. Koran and Elias National Institute of Mental Health. “FY 2019 Budget Congressional Justification,” 2019 Budget Congressional National Institute of Mental Health. “FY October 2018, Anatomy of NIMH Funding,” National Institute of Mental Health, accessed Thomas R. Insel. “The “25th Annual OCD Conference Registration,” Annual OCD Conference “25th 2018, accessed October Disorders, International College of Obsessive Compulsive Spectrum (TWGs),” Groups Networks and Thematic Working “ECNP In schizophrenia, another complicated psychiatric disorder, risk genes were first identified in genome-wide association risk genes were another complicated psychiatric disorder, In schizophrenia, and Informatics Institute. “About Enigma,” USC Mark and Mary Stevens Neuroimaging The Enhancing Neuroimaging Global Initiatives in Neurogenetics: and Paul M Thompson. “Emerging Carrie E. Bearden S. Evelyn Stewart, et al. “Genome-wide association study of obsessive compulsive disor S. Evelyn Stewart, et al. “Genome-wide association Heidi A. Browne, Shannon L. Gair, Jeremiah M. Scharf, and Dorothy E. Grice. “Genetics of obsessive compulsive disorder and and E. Grice. “Genetics of obsessive compulsive disorder and Dorothy M. Scharf, Jeremiah Shannon L. Gair, A. Browne, Heidi Narrative Review” A Studies in Obsessive Compulsive Disorder: “Neuroimaging Arpit Parmar and Siddharth Sarkar. Christopher Pittenger. “Glutamatergic Agents for OCD and Related Disorders.” Agents for OCD and Related Disorders.” “Glutamatergic Christopher Pittenger. Zoya Marinova, De-Maw Chuang and Naomi Fineberg. “Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Drugs “Glutamate-Modulating Fineberg. Zoya Marinova, De-Maw Chuang and Naomi Vlasios Brakoulias, Vladan Starcevic, Amparo Belloch, Chris Brown, Ygor Arzeno Ferrao, Leonardo F. Fontenelle , C. Lochner, Fontenelle , C. Lochner, F. Arzeno Ferrao, Leonardo Ygor Belloch, Chris Brown, Amparo Starcevic, Vlasios Brakoulias, Vladan Christopher Pittenger. “New Horizons in OCD Research and the Potential Importance and the Potential “New Horizons in OCD Research Michael H. Bloch, Vladimir Coric, and Christopher Pittenger.  Ibid. The Brain and Behavior Research Foundation. Accessed October 2018, Accessed October Foundation. Research The Brain and Behavior Compulsive Disor National Institute of Mental Health. “Obsessive National Institute of Mental Health. “Obsessive Compulsive Disor National Institute of Mental American Psychiatric Association. American Psychiatric  National Institute of Mental Health. “Obsessive compulsive Disor National Institute of 22 20 21 18 19 17 16 15 14 12 13 10 11 9 7 8 5 6 4 2 3 1 ENDNOTES Endnotes 55 74, 32, no Indian 7, no. 3 Indian Indian 32, no. 3 (2008): JAMA Psychiatry JAMA Translational Psychiatry Translational Angela R. Laird, Sarah M. Sarah Angela R. Laird, . (Santa Monica, CA: RAND http://scitechconnect.elsevier.com/ Neuroscience & Biobehavioral Reviews Neuroscience 81, no. 10 (2017): 375-376. . Neuroscience & Biobehavioral Reviews Neuroscience oteins and OCD, see Sophia Attwells, Elaine oteins and OCD, see Sophia , (July 23, 2015): ch Portfolio Online Reporting Tools (RePORT). Projects Projects (RePORT). Online Reporting Tools ch Portfolio Biological Psychiatry 175, no 5 (2018): 453-462. , no 6137 (2013): 1234-1239. SciTech Connect, Elsevier SciTech . https://perma.cc/BSD9-RR6Y 65, no.1 (2009): 75-83. Science 340 23, no. 3 (2000): 563-86. 38, no. 5 (2016): 386-394. 38, no. 5 (2016): 386-394. R. Chamberlain, 38, no. 5 (2016): 386-394; Lara Menzies, Samuel . American Journal of Psychiatry Biological Psychiatry Project Ecosystem: Mapping the global mental health research funding system Ecosystem: Mapping the global mental health research Project https://perma.cc/EP3H-TRL4 Psychiatric Clinics of North America Spellman, Neria L. Douglass, Mazen Ahmari, Timothy striatum. Susanne E. cortex and ventromedial between the orbitofrontal and René Hen. “Repeated cortico-striatal stimulation A. Gordon, Joshua A. Kheirbek, H. Blair Simpson, Karl Deisseroth, generates persistent OCD-like behavior.” response to various stimuli or during performance of cognitive tasks. Lara Menzies, Samuel R. Chamberlain, Angela R. Laird, Angela R. Laird, to various stimuli or during performance of cognitive tasks. Lara Menzies, Samuel R. Chamberlain, response and neuropsychological neuroimaging “Integrating evidence from Bullmore. Sarah M. Thelen, Barbara J, Sahakian, Ed T. model revisited.” the orbitofronto-striatal studies of obsessive compulsive disorder: 3 (2008): 525-549. obsessive compulsive disorder: the orbitofronto-striatal model revisited.” model revisited.” the orbitofronto-striatal obsessive compulsive disorder: 525-549. neurobiology-basis-of-ocd/ Journal of Psychological Medicine were most prominent in the corpus callosum and the left superior longitudinal fasciculus, but appeared in other brain and the left superior longitudinal fasciculus, but appeared in the corpus callosum most prominent were Chan, and X. Zhu. R.C.K. C. Tan, Wang, Yi Wang, Ya Liu, C. Niu, S. Cai, L. Zou, as well. J. Gan, M. Zhong, J. Fan, W. regions connectivity in adults with obsessive compulsive disorder,” “Abnormal white matter structural (2017). Journal of Psychological Medicine studies of and neuropsychological neuroimaging “Integrating evidence from Bullmore. Thelen, Barbara J, Sahakian, and Ed T. orbitofrontal cortices in patients with OCD. Jean-Yves Rotge, Dominique Guehl, Bixente Dilharreguy, Jean Tignol, Bernard Bernard Jean Tignol, Rotge, Dominique Guehl, Bixente Dilharreguy, with OCD. Jean-Yves cortices in patients orbitofrontal volume changes in obsessive Aouizerate. “Meta-analysis of brain Burbaud, and Bruno Pierre Allard, Bioulac, Michele compulsive disorder,” Journal of Psychological Medicine Pittsburgh Medical Center, (October 7, 2016): Medical Center, Pittsburgh Abnormalities Boedhoe et al. “Cortical S.W. common. Premika more were area in surface pediatric patients, reductions Obsessive compulsive the ENIGMA Findings From Adult Obsessive compulsive Disorder: Pediatric and Associated With Group.” Working Disorder Setiawan, Alan A. Wilson, et al., “Inflammation in the Neurocircuitry of Obsessive compulsive Disorder,” of Obsessive compulsive Disorder,” et al., “Inflammation in the Neurocircuitry Wilson, A. Alan Setiawan, more and examined the cortex of Group Working Another study was conducted by the ENIGMA-OCD no. 8 (2017): 833-840. Schmaal, Paul Daniel Boedhoe, Lianne S.W. people without OCD, see Premika to 1,700 OCD compared than 1,900 people with From Findings compulsive Disorder: Adult Obsessive Pediatric and Associated With Abnormalities Arnold, et al., “Cortical Group,” Working compulsive Disorder Obsessive the ENIGMA and Steven Wooding. Corporation, 2016): Veterans Affairs (VA) for a total of $37,661,709. Of the 105 projects, 72 are being funded by NIMH for a total of $27,474,985; 18 being funded by 72 are Of the 105 projects, for a total of $37,661,709. Affairs (VA) Veterans being 15 are and the remaining and Stroke; Disorders Institute of Neurological the National funded through being are projects and seven other NIH entities. NIH’s Office of the Director, the VA, funded through (2017). pr caused by elevated levels of translocator between brain inflammations containing the keywords “obsessive compulsive disorder(s)” and “obsessive compulsive disorder” were queried in RePORTS. queried in RePORTS. were disorder” compulsive and “obsessive disorder(s)” compulsive “obsessive the keywords containing States Department of NIH and the United various agencies under by being administered projects yielded 105 The search Sanjaya Saxena and Scott L. Rauch. “Functional neuroimaging and the neuroanatomy of obsessive compulsive disorder.” of obsessive compulsive disorder.” and the neuroanatomy Sanjaya Saxena and Scott L. Rauch. “Functional neuroimaging was used to stimulate connections activate specific neurons, and reversibly Optogenetics, which uses light to precisely Ibid. Ibid. cortex in patients with OCD in activation of within the orbitofrontal meta-analysis of 15 prior studies found abnormal A Caitlin Beddows. “Neurobiology Basis of OCD,” Caitlin Beddows. “Neurobiology Narrative Review.” A Studies in Obsessive Compulsive Disorder: “Neuroimaging Arpit Parmar and Siddharth Sarkar. Arpit Parmar and Siddharth Sarkar. “Neuroimaging Studies in Obsessive Compulsive Disorder: A Narrative Review.” A Studies in Obsessive Compulsive Disorder: “Neuroimaging Arpit Parmar and Siddharth Sarkar. A combined analysis of past studies found structural abnormalities in the left anterior cingulate cortex and the left and right abnormalities combined analysis of past studies found structural A Narrative Review,” A Studies in Obsessive Compulsive Disorder: “Neuroimaging Arpit Parmar and Siddharth Sarkar. in patients abnormalities Microstructural in 24 people with OCD to 23 healthy controls. brain structure The study compared “University of Pittsburgh Brain Institute Receives Grant from Hillman Foundation to Advance Brain Research,” University og Research,” Advance Brain Foundation to Hillman Brain Institute Receives Grant from “University of Pittsburgh among medicated whereas controls, thinner than in healthy of the cortex were In medicated adults with OCD, regions Alexandra Pollit, Gavin Cochrane, Anne Kirtley, Joachim Krapels, Vincent Larivière, Catherine A. Lichten, Sarah Parks, Catherine Larivière, Joachim Krapels, Vincent Anne Kirtley, Alexandra Pollit, Gavin Cochrane, Giving USA and Lilly School of Philanthropy. “Giving USA 2017: The Annual Report on Philanthropy for the Year 2016,” Year for the Annual Report on Philanthropy 2017: The USA “Giving of Philanthropy. and Lilly School Giving USA an association Foundation include a study that revealed with the Brain and Behavior Research Recent studies associated Ibid. Resear of Health’s (NIH) based on National Institute Information 40 39 38 36 37 34 35 33 32 31 30 29 28 27 26 25 23 24 Endnotes 56 30, no. Michael

Neuroscience & Neuroscience Susanne E. Ahmari, Susanne E.

Katherine M. Nautiyal,

147B, no. 4 (2008): 473-478. Holly Moore,

, no. 6137 (2013): 1243-1246. , no. 6137 (2013): Daniel Flicker,

Science 340 USA 114, no 22 (2017): 5719-5724. 114, USA Kenji Fransis Tanaka,

33, no. 3 (2016): 179-191. 51, no 4 (1994): 302-308. Emily N. Krasnow,

Gregg Stanwood, Gregg

80, no. 7 (2016): 522-33. Jared M. Kopelman, Jared

Carrie K. Jones,

57, no. 8 (2000): 794-801. 57, no. 8 (2000): 794-801. Translational Psychiatry 8, no. 1 (2018): 191. Translational American Journal of Medical Genetics Par B Neuropsychiatric Genetics American Journal of Medical Genetics Par B Neuropsychiatric 32, no. 8 (2015): 550-562. 32, no. 8 (2015): 550-562. 32, no. 8 (2015): 550-562. 52 (2015): 74-88. Muhammad O. Chohan,

Christoph Kellendonk,

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Bubser, and of the National Academy of Sciences Proceedings behavior,” stereotypic related disorders,” Psychiatric Clinics of North America 37, no. 3 (2014): 319-335. disorders,” related checking, researchers found evidence that specific genetic and environmental factors underlie contamination symptoms. factors found evidence that specific genetic and environmental checking, researchers “Heritability of obsessive compulsive I. Boomsma, John M. Hettema, and Kenneth S. Kendler. Dorret grootheest, Daniël S. Van symptom dimensions,” genetics was found to account for the Shared superstition, counting/checking, and hoarding. rumination, symmetry/ordering, which had unique genetic factors. Christie L. Burton, Laura S. Park, heritability of the traits, with the exception of hoarding, Tara Goodale, S.M. Shaheen, Vanessa M. Sinopoli, Janet Shan, Annie Dupuis, Elizabeth C. Corfield, Nadine Forget-Dubois, Arnold, “Heritability of obsessive compulsive trait dimensions in youth from and Paul D. 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Fontenelle, Izabela Leonardo with OCD to 40 healthy controls. inflammatory markers in 40 adults compared Researchers compulsive Disor National Institute of Mental Health. “Obsessive Using PET imaging to detect activated microglia, immune cells associated with inflammation in the nervous system, immune cells associated with inflammation Using PET imaging to detect activated microglia, between the ages of 8 and 19 with early-onset OCD to 47 healthy inflammatory markers in 102 patients compared Researchers In schizophrenia, another complicated psychiatric disorder, risk genes were first identified in genome-wide association first risk genes were psychiatric disorder, another complicated In schizophrenia, review,” PANS: a systematic PANDAS and of “Treatment Bejerot. Sofia Sigra, Eva Hesselmark, and Susanne Carolina CappiC. Cappi, Helena BrentaniH. Brentani, Leandro De Araujo LimaL. Lima, S.J. Sanders, G. Zai, Juliana Belo Araujo LimaL. Lima, S.J. Sanders, G. 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. 32, no. 4 (2016): 262-266. https://www.herox.com/ https://www.rockpa.org/wp-content/ : . https://www.fda.gov/newsevents/ Journal of ECT . U.S. National Library of Medicine U.S. National Library of , accessed August 17, 2018, , accessed . . 14 (2014): 214. 14 (2014): 214. https://www.brainsway-global.com/news_events/brainsway-receives-first-ever-fda- https://www.fastercures.org/reports/view/16 BMC Psychiatry BMC Psychiatry . US Food and Drug Administration , accessed October 2018, , accessed October (2013), accessed August 2018, August (2013), accessed “Clinical Trial Guidelines: The Challenge Breakthrough,” Herox, accessed August 2018, accessed Herox, Breakthrough,” Guidelines: The Challenge “Clinical Trial ClinicalTrials/guidelines Funders of Medical Research,” for Nonprofit Toolkit A Impact: “Measuring and Improving Institute For more information on donor collaboration and more case studies across a number of fields, see RPA’s recent report recent number of fields, see RPA’s a case studies across and more information on donor collaboration For more Learning for for Impact, Approaches Shifting Systems: Approaches Scaling Solutions Toward uploads/2018/10/10-20-RockPA-Scaling-Solutions-02-WEB-1.pdf Resistance Obsessive Compulsive Disorder (OCD) Subjects,” (OCD) Subjects,” Disorder Resistance Obsessive Compulsive https://clinicaltrials.gov/ct2/show/NCT01343732 Guimarães, Perminder Sachdev, Sujit Sarkhel, and Quirino Cordeiro. “Transcranial Magnetic Stimulation for Obsessive Magnetic “Transcranial Cordeiro. Sujit Sarkhel, and Quirino Sachdev, Guimarães, Perminder Meta-analysis.” An Updated Systematic Review and compulsive Disorder:    clearance-of-a-non-invasive-device-for-treatment-of-obsessive compulsive-disorder222/ clearance-of-a-non-invasive-device-for-treatment-of-obsessive compulsive disorder,” newsroom/pressannouncements/ucm617244.html Lenartz, Veerle Visser-Vandewalle, and Jens Kuhn. “Deep brain stimulation for treatment-refractory obsessive compulsive obsessive for treatment-refractory “Deep brain stimulation and Jens Kuhn. Visser-Vandewalle, Lenartz, Veerle review,” a systematic disorder: Ltd. BrainsWay ClinicalTrials.gov. “Tolerability, Safety and Efficacy of the HAC-Coil Deep Transcranial Magnetic Stimulation in Medication Transcranial Magnetic Stimulation in and Efficacy of the HAC-Coil Deep Safety “Tolerability, ClinicalTrials.gov. Alisson Paulino Trevizol, Pedro Shiozawa, Ian A. Cook, Isa Albuquerque Sato, Kaku, Caio Barbosa Kaku, Fernanda B.S. Sato, Kaku, Albuquerque A. Cook, Isa Ian Shiozawa, Pedro Alisson Paulino Trevizol,

US Food and Drug Administration. “FDA permits marketing of transcranial magnetic stimulation for treatment of obsessive stimulation for treatment permits marketing of transcranial magnetic Administration. “FDA US Food and Drug  “BrainsWay Receiveds First Ever FDA Clearance of a Non-Invasive Device for Treatment of Obsessive Compulsive Disorder,” Disorder,” of Obsessive Compulsive for Treatment a Non-Invasive Device Clearance of First Ever FDA Receiveds “BrainsWay 102 101 100 99 98 97 96