Research is vital to our goals of better understanding OCD and related disorders, and improving treatment. To help achieve these goals, the IOCDF awards research grants to promising studies thanks to generous donors from within the OCD community.
Since 1994, the IOCDF has awarded over $7 million in research grants, and continues to offer research grant awards annually. The Michael Jenike Young Investigator Awards, which help build OCD research programs and keep junior researchers interested in studying the field of OCD and related disorders, are offered every year. The Breakthrough and Innovator Awards, which fund the work of senior researchers as they pursue large-scale projects that help us better understand and treat OCD, are offered in alternating years.
What can an IOCDF Research Grant Award help us learn about OCD and related disorders?
Jonathan S. Abramowitz, PhD, ABPP, discusses his IOCDF grant-funded research into couple-based cognitive behavioral therapy for people with obsessive-compulsive disorder (OCD).
2020 Research Grant Awardees
We are excited to announce the 2020 IOCDF Research Grant awardees! This year, we awarded over $1.1 million in funding to researchers pursuing exciting and impactful projects on a range of topics in OCD and related disorders. To read more about their projects, click "2020 IOCDF Research Grant Award Winners" below!
Identifying targets for prevention and early intervention in Obsessive-Compulsive Disorder
David Mataix-Cols, PhD
Award amount: $500,000
We still do not know exactly what causes OCD. Research has found that the risk for developing OCD is not only due to the genes we inherit from our parents, but also due to factors in our environment that can’t be explained by genetics alone. In fact, researchers believe that at least 50% of the risk for developing OCD comes from what we experience in the environment around us, but we do not yet know which environmental factors increase this risk. Dr. Mataix-Cols and his team will recruit a large number of identical twin pairs where one twin has OCD and one does not. This means that the twins share exactly the same genes, but one twin experienced something in their environment that caused them to develop OCD, while the other did not. With the consent of study participants, Dr. Mataix-Cols and his team will access a vast amount of medical information about them using the unique Swedish nationwide register, which collects the medical records of Swedish citizens throughout their lives. They will also build a database of biological samples from each participant, including samples that were taken at birth for the Swedish phenylketonuria (PKU) screening biobank. The project team will then analyze this data to attempt to identify the environmental causes that increase risk for developing OCD. This research project could unlock new information about why certain people develop OCD, and even lead to knowledge that would allow us to prevent OCD from taking hold in the first place
A Precision Medicine Approach to OCD Treatment: Targeting Neuroinflammation
Jeffrey Miller, MD
Research Foundation for Mental Hygiene, Inc. / Columbia University
New York, New York
Award Amount: $500,000
Dr. Miller and his team will test a new OCD treatment strategy by measuring and targeting inflammation in the brain. Their work builds off of early evidence suggesting a connection between OCD and brain inflammation, and the possible benefits of anti-inflammatory medication. Dr. Miller’s project will precisely measure brain inflammation in a group of people with OCD using PET imaging and blood sampling, and then provide them with treatment using the anti-inflammatory drug celecoxib (the brand name drug Celebrex). Their symptoms will be tracked, and their levels of brain inflammation will be measured after treatment using the same brain imaging and blood sampling techniques as those employed before treatment. Dr. Miller’s work will substantially add to our knowledge about the role that inflammation may play for some people with OCD, and whether anti-inflammatory medication could be an effective treatment for these individuals.
Young Investigator Awards
Using a Machine Learning Approach to Identify Immune Biomarkers Associated with PANS/PANDAS
Lauren Breithaupt, MD, PhD
Massachusetts General Hospital / Harvard Medical School
Within the past twenty years, researchers and clinicians have begun to recognize that certain cases of childhood-onset OCD are unique. In these cases, a child’s OCD symptoms appear very rapidly, and typically set in following an infection like strep throat. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric Autoimmune Neuropsychiatric Syndrome (PANDAS/PANS) are proposed diagnoses for these unique pediatric illnesses, and are distinct from a diagnosis of childhood OCD. However, clinicians and researchers often struggle to differentiate OCD and PANDAS/PANS, in part because there is no biological test to confirm that a child indeed does have PANDAS/PANS. In this research study, Dr. Breithaupt will analyze a very large set of biological data from a group of children with PANDAS/PANS, a group of children with PANDAS/PANS who have symptoms that make it difficult for them to eat (avoidant/restrictive food intake disorder, or ARFID), as well as a group of children with more typical childhood OCD, and a group of healthy children. Her approach uses machine learning—a form of artificial intelligence— to sift through this large volume of data and find hidden patterns in it. Her goal is to identify proteins in the blood that could serve as a unique marker that a child has PANDAS/PANS, which could not only lead to a new diagnostic test, but also provide useful information for the development of new medications.
Understanding and treating OCD in older adults
Carly Johnco, PhD
Almost all of the research on OCD, including how it is best treated, has been focused on children and adults under the age of 65. Very little attention has been given to OCD in older adults. With the population ageing globally, the number of older adults with OCD is expected to double within the next thirty years. We currently lack important information about the best possible ways to treat the growing number of older adults with OCD, and how approaches that work with children and adults may need to be modified to best serve older adults. Dr. Johnco’s project will focus on family accommodation (when a family member of a person with OCD helps that person with their rituals). Accommodation in childhood and adult OCD is well understood, and treatment approaches now commonly involve family members in order to reduce accommodation from family and help their loved one recover from OCD. Older adults have an increased need for support from a variety of people, including their adult children, health care workers in the home or in a residential setting, neighbors, and others, all of whom are not the typical sources of accommodation for younger people with OCD. This study will investigate the ways that accommodation plays a role in the lives of older adults with OCD, and Dr. Johnco will develop a treatment protocol for addressing accommodation that is age-appropriate and considers the unique circumstances of aging with this disorder.
Intervening on Loneliness to Reduce Object Attachment in Hoarding Disorder: Two Randomized Controlled Pilot Studies
Keong Yap, DPsych
University of New South Wales
Award amount: $48,000
People with hoarding disorder experience strong emotional attachment to their possessions and extreme difficulty and distress when throwing things away. This can lead to accumulation of possessions beyond the norm, to the point where the homes of people with hoarding disorder can become difficult to move around in, or even unsanitary and potentially dangerous. One possible explanation for the strong emotional attachment to possessions in Hoarding Disorder is loneliness: people with hoarding disorder bond with their possessions in order to replace the bonds with other people that are missing from their lives. The social impacts of hoarding disorder may deepen these feelings of loneliness by making it difficult to form or sustain healthy relationships. Dr. Yap’s research will attempt to address loneliness in people with hoarding disorder through an online program that is known to be effective in reducing feelings of loneliness. He will then track participants’ loneliness and depression symptoms, as well as their symptoms of hoarding, to find out whether addressing loneliness can be a helpful intervention for hoarding disorder.
Previous IOCDF Research Grant Recipients
The generosity of our donors has made it possible for us to provide sustained support for OCD and related disorders research for the past 26 years. Over 100 projects have been funded on a wide range of important topics. You can learn more about the research that the IOCDF funds by reading the project summaries below.
Research funded by the IOCDF:
Breakthrough Award Winners:
Clinical Trial of Image-Guided Low-Intensity Focused Ultrasound Pulsation (LIFUP) for the Treatment of Obsessive Compulsive Disorder (OCD)
Wayne Goodman, MD
Baylor College of Medicine
Darin Dougherty, MD
Massachusetts General Hospital
Project Description: About one in three people with OCD do not get better after trying first-line treatments. For patients with severe, treatment-resistant OCD, Deep Brain Stimulation (DBS) is an effective option, but requires surgery to implant electrodes within the brain and a pacemaker-like controller in the chest. Dr. Goodman and Dr. Dougherty are studying a new brain stimulation technique (LIFUP) that could mimic the effects of DBS but uses ultrasound to stimulate the brain, eliminating the need for surgery. This study will evaluate the safety and effectiveness of LIFUP in a group of 24 patients who have tried both ERP and at least two SSRIs but continue to experience OCD symptoms.
Pilot Study of the Glutamate AMPAR Modulator RR-HNK in OCD
Carolyn Rodriguez, MD, PhD
Project Description: Currently available medications for OCD take up to two to three months to begin working and rarely relieve 100% of patients’ symptoms. Dr. Rodriguez is investigating new medications that could begin working faster and relieve OCD symptoms more completely. In a pilot study of ketamine as a treatment for OCD, she found that patients experienced immediate relief from symptoms after a single dose of ketamine, and that 50% reported the beneficial effects lasting one week or more. This grant funds a trial of an experimental drug (RR-HNK) that could potentially mimic the therapeutic effects of ketamine without side effects like nausea and disassociation.
Innovator Award Winners:
Assessing correlates of neuroinflammation in children with PANDAS, obsessive compulsive disorder, and healthy controls using Magnetic Resonance Imaging
Kyle Williams, MD, PhD
Massachusetts General Hospital
Project Description: Inflammation of the brain is suspected to be present in children with PANDAS, but confirming this hypothesis is difficult. The best tools for revealing brain inflammation expose patients to ionizing radiation, which limits their use generally, but especially in children. Dr. Williams will use a new and innovative technique to measure inflammation with MRI, which emits no ionizing radiation. His study will compare children with PANDAS to children with pediatric- onset (non-PANDAS) OCD, as well as healthy children, to further our understanding of the role that inflammation plays in PANDAS.
Towards optimal use of internet-delivered interventions for obsessive compulsive disorder
Bethany Wootton, PhD
University of Technology Sydney
Project Description: Cognitive behavioral therapy (CBT), including exposure and response prevention, is a proven and effective treatment for OCD. However, many people with OCD are not able to access effective treatment that is both affordable and located near where they live. Internet-based CBT has helped overcome many barriers to access, but we do not know much about which patients are best suited to try an internet-delivered approach. Dr. Wootton’s research will evaluate which patients respond best to internet-delivered CBT, and will help clinicians match patients to these services in a safer and more effective way.
Young Investigator Award Winners:
Circadian Rhythm Changes as a Predictor of OCD Symptom Severity and Outcome in Residential Treatment
Jacob Nota, PhD
McLean Hospital / Harvard Medical School
Project Description: Problems with sleep — in particular a delayed sleep cycle where a person falls asleep late at night and wakes up in the late morning or early afternoon — have been associated with more severe OCD symptoms and poorer outcomes in treatment. Dr. Nota’s research will help clarify the cause and effect relationship between sleep and OCD symptoms, and what role sleep plays in patients with severe and treatment-resistant OCD. Findings from this project will reveal whether changing sleep patterns could help patients recover from OCD, and whether sleep-based interventions should be added on top of standard OCD treatments.
Celecoxib as an adjunct to treatment as usual in childhood-onset OCD: A double-blind randomized controlled trial
Clara Westwell-Roper, MD, PhD
British Columbia Children's Hospital Research Institute
Project Description: Non-steroidal anti-inflammatory drugs (NSAIDs) like celecoxib (sold under the brand name Celebrex) are increasingly recommended by physicians as a treatment for children with PANDAS/PANS, and there is early evidence that celecoxib could help adults with OCD. Dr. Westwell-Roper will conduct a randomized controlled trial of celecoxib as a treatment for childhood-onset OCD—the first study of its kind—to test whether it is a safe and effective treatment for this population.
Identification of Peripheral Biomarkers of Antidepressant Response in Obsessive Compulsive Disorder
Gwyneth Zai, MD, PhD
Centre for Addiction and Mental Health
Project Description: Many people with OCD who take medication to manage their disorder need to try several different medications before finding one that works. This means months or even years of trying — and failing — to find effective treatment for their symptoms. Dr. Zai’s research seeks to reveal biomarkers that can be identified through a blood test, and could predict the type of antidepressant that will work best for each unique patient. Matching patients with effective medication immediately could dramatically improve outcomes for many people with OCD.
Breakthrough Award Winner:
Identifying the molecular and cellular substrates of OCD using human post-mortem brain
Susanne Ahmari, MD, PhD
University of Pittsburgh
Award amount: $500,000
Obsessive compulsive disorder (OCD) is a chronic, severe mental illness that affects 2-3% of people worldwide. Brain imaging studies in OCD patients have consistently shown abnormal activity in regions involved in decision-making (orbitofrontal cortex [OFC]) and gating of sensory information to the cortex (thalamus). However, we have no knowledge regarding the molecular changes in these regions that contribute to abnormal function in people who suffer from OCD. We therefore performed targeted gene expression studies to fill this gap. Our preliminary findings in OFC demonstrate coordinated down-regulation of genes associated with excitatory synaptic transmission, which begs the question: What is causing these concerted changes? One cohesive explanation is that an OFC input structure– i.e. thalamus– is the primary source of molecular changes, and that the coordinated transcriptional downregulation in OFC is compensatory. Here we propose experiments to test this hypothesis using RNA-sequencing in post-mortem OFC and thalamus brain tissue from OCD patients and matched unaffected comparison subjects. This unbiased approach will allow us to assess differential gene expression, gene co-expression, and perform pathway analysis to uncover the biological networks most affected in OCD patients. Together, these experiments will allow us to identify key molecular pathologic changes underlying OCD, with the ultimate goal of finding novel targets and developing more effective treatments.
Young Investigator Award Winners:
Neural Mechanisms of Avoidance in Exposure and Response Prevention for OCD
Martha Falkenstein, PhD
Co-mentors: Courtney Beard, PhD and Christian Webb, PhD
McLean Hospital/Harvard Medical School
Award amount: $39,766
Many patients with OCD who successfully complete exposure and response prevention (ERP) treatment experience life-changing improvements in their OCD symptoms. However, as many as 40-50% of patients do not experience a significant recovery. Dr. Falkenstein’s research will concentrate on enhancing treatment outcomes for this group, with a specific focus on addressing the avoidance behaviors that are common among people with OCD. This study will involve approximately 70 participants receiving ERP for OCD at Mclean Hospital’s OCD Institute. A subset of these participants will receive “approach-avoidance training” in addition to ERP. In this training, participants will use a joystick to “pull” images associated with their OCD triggers toward them, and “push” neutral images away from them, with the goal of teaching them to automatically approach -- rather than avoid -- feared situations and experiences. In previous research, a similar training was shown to have an effect after just one 15-minute session. Dr. Falkenstein’s research will investigate whether ERP treatment outcomes can be improved with the addition of this training.
A Virtual Reality Study of Cognitive Biases in Body Dysmorphic Disorder
Berta Summers, MA
Mentor: Sabine Wilhelm, PhD
Massachusetts General Hospital/Harvard Medical School
Award amount: $44,856
Everyone has experienced a distressing social interaction at some point in their lives. This could take the form of judgement or criticism from coworkers or classmates, anger from another driver on the road, or discomfort when dealing with a pushy salesperson. For most people, it’s fairly easy to distinguish these interactions from the many benevolent or neutral social situations that we find ourselves in on a daily basis. However, research has found that people with BDD often assign negative interpretations to neutral or benign social interactions, and may believe that others are judging them or making fun of them when they are in fact not. Berta Summers, a researcher at Massachusetts General Hospital, will further investigate this phenomenon by presenting simulated social interactions to patients with BDD using virtual reality technology. Her research will investigate the role these negative interpretations play in BDD, and how virtual reality could be employed in the future to enhance BDD treatment.
Active avoidance of threat cues and fear extinction in obsessive compulsive disorder
Michael Wheaton, PhD
Mentor: Blair Simpson, MD, PhD
New York, NY
Award amount: $50,000
Past research has shown that we can learn to be afraid of things that we encounter, and that we can also modify our fears through exposure. New research has shown that when healthy people are able to perform some type of action in order to avoid a threat, they may become less fearful when confronted with different, future threats. This type of avoidance is called “active avoidance.” Many compulsive behaviors in OCD could be considered forms of “active avoidance.” However, we know that when OCD patients engage in compulsions, these behaviors reinforce, rather than diminish, their fears. Additionally, when they perform compulsions in the context of ERP treatment, the treatment becomes less effective overall.
Dr. Wheaton’s research will test active avoidance and fear responses in people with OCD -- the first study of its kind. In order to test this, research participants, some of whom have OCD, will be shown images, and receive mild electric shocks in order to evoke a fear response which can then be measured. Some participants will have the opportunity to learn how to avoid the shocks (active avoidance), while other participants will continue to receive the shocks until the participants in the active avoidance group learn how to avoid them. Dr. Wheaton and his team will compare the fear responses in these two groups with those of healthy control subjects and people with OCD. They expect to find that active avoidance is less effective in reducing fear response in people with OCD when compared to healthy individuals. This study is an important step toward future brain imaging research that will investigate the underlying brain circuitry in OCD, as well as the development of fear response tests that may predict treatment outcomes and allow clinicians to create more effective, individualized treatment plans for OCD patients.
Obsessive-Compulsive Symptoms in African American Young Adults: The Roles of Racial Discrimination and Racial Identity
Henry Willis, MA
Co-mentors: Enrique Neblett, PhD and Jonathan Abramowitz, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC
Award amount: $25,826
Past research has shown that people with OCD experience worsened symptoms when under stress. Many forms of stress exist and are common in daily life, but some stressors are unique to our identities and our status in a larger society. For African Americans in the United States, racial discrimination is one of these unique stressors. In this research project, Henry Willis will investigate the role of racial discrimination in the intrusive thoughts experienced by African Americans with OCD. He will also examine whether African Americans who hold a sense of belonging and commitment to a larger group defined by their race -- a racial identity -- may be less likely to develop certain OCD symptoms. This project will contribute to what has so far been a limited body of research, and may inform future treatment for this population of OCD patients.
The Impact of Obsessive-Compulsive Disorder on Education, Labor Market Marginalization, and Societal Cost
Lorena Fernandez de la Cruz, PhD
Assistant Professor, Karolinska Institutet
Award Amount = $38,510
Obsessive-Compulsive Disorder (OCD) typically emerges in childhood or adolescence, may be chronic, and is associated with marked functional impairment, reduced quality of life, and high economic burden for society. The impact of OCD on educational attainment, labor market marginalization (i.e., receipt of disability pension, periods of sickness absence, or unemployment), and their associated socioeconomic costs are suspected to be considerable, but previous research has been scarce and severely limited by a range of methodological problems. We will analyze data from the Swedish national registers covering a period of 16 years (1997-2013) and including over 30,000 individuals diagnosed with OCD in order to investigate the following impacts: 1) academic performance after compulsory education and highest level of education achieved by these individuals, compared to the general population and their unaffected siblings; 2) labor market entry and marginalization (i.e., receipt of disability pension, periods of sickness absence, or unemployment) in individuals diagnosed with OCD and in their parents; and 3) economic costs for society. We expect that the results will stimulate connections between policy-makers, vocational rehabilitation, and mental health services in order to design and implement specific intervention strategies with the eventual aim of improving the patients and their relatives’ quality of life and reducing economic societal costs.
Decision-Making Impairments in OCD: An Integrated Behavioral Economics Model
Ryan Jacoby, MA
Clinical Fellow in Psychology
Massachusetts General Hospital/Harvard Medical School
Award Amount = $35,039
Previous research indicates that individuals with Obsessive Compulsive Disorder (OCD) demonstrate impairments when making ambiguous decisions, but not with risky decisions in which outcome probabilities are known. Thus, in the service of ultimately tailoring psychological interventions to improve patient performance in ambiguous scenarios, the proposed interdisciplinary study draws insights from economic Decision Science theories and psychological models of intolerance of uncertainty (IU), a key cognitive bias in OCD. The purpose of this investigation is to examine whether conditions of ambiguity during decision-making may prime IU beliefs and lead to worse decision-making for individuals with OCD. Specifically, we expect that patients with OCD (relative to non-psychiatric controls) will devalue (i.e., avoid) decisional options that entail ambiguity (relative to those only involving risk). Furthermore, we will explore the association between IU beliefs and two differing strategic responses to ambiguity – information gathering vs. escape/avoidance. Finally, we will investigate whether ambiguity aversion is uniquely associated with certain OCD symptom dimensions (e.g., responsibility for harm). Findings could aid in future research on neural mechanisms of decision-making in OCD and inform treatment of this debilitating psychiatric condition.
Use of Transcranial Direct Current Stimulation to Enhance Consolidation of Therapeutic Learning in Obsessive-Compulsive Disorder (OCD)
Thomas Adams, PhD
Yale University School of Medicine
Award Amount = $48,646
Abstract: Available treatments for obsessive-compulsive disorder (OCD) are limited; medications and psychotherapy can each help about 60% of patients but troubling symptoms often persist even among treatment responders. New therapeutic strategies are urgently needed. The psychosocial treatment of choice for OCD is exposure and response prevention (ExRP), which is likely dependent upon the acquisition and consolidation of extinction learning. Extinction learning is mediated by a well-defined circuit encompassing the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This raises the exciting possibility that direct engagement of this circuitry might enhance therapeutic learning and memory. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment synaptic plasticity, learning, and memory. The proposed study will enroll 24 OCD patients who will complete a novel behavioral paradigm that encapsulates the core features of ExRP for OCD, to test whether tDCS applied to the medial prefrontal cortex following therapeutic exposure enhances consolidation of therapeutic learning. If successful, the demonstration of such an interactive effect would constitute a powerful translation from basic mechanistic observations to a clinical advance that would motivate a larger-scale clinical trial.
Explicating the Influence of Object Attachment in Hoarding Disorder
Melissa Norberg, PhD
Macquarie University, Sydney, Australia
Award Amount: $49,310
After completing cognitive behavioral treatment (CBT), many patients continue to experience clinically significant hoarding symptoms, with the clutter in their homes remaining virtually unchanged. In addition, very little research has examined why individuals who hoard become attached to objects. Current treatment challenges the importance of objects, but does not address why individuals are attached to objects. Our recent research demonstrates that excessive object attachment may be the primary cause of saving, and thus, might be a key target for improving treatment. Some research suggests that individuals with an insecure attachment to people may turn to objects for support because people are unreliable and rejecting. Furthermore, according to one theory, viewing objects in human-like terms allows objects to restore needs of belonging. This project brings together these disparate fields to test our overarching hypothesis that social exclusion leads to object attachment, and that this relationship will be stronger for individuals who experience more attachment anxiety. Additionally, this project will examine if social over-inclusion leads to less object attachment. Our results could substantially advance the cognitive-behavioral model of hoarding disorder and also provide a pathway for improving current treatment.
PANDAS Autoantibodies and the Blood-Brain Barrier
Dritan Agalliu, PhD
Columbia University Medical Center, New York, NY
Award Amount: $43,500
Infections with S. pyogenes (GAS) are associated with brain autoimmune disorders: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Autoantibodies form when the immune system fails to recognize the body’s own cells and tissues as “self” and attacks healthy tissue. Autoantibodies that recognize neuronal targets are found in acutely ill children with SC or PANDAS; however, how these autoantibodies cross the blood-brain barrier (BBB) remain unclear. We have found that GAS-specific immune cells in mice enter the brain, cause BBB breakdown, and allow circulating autoantibodies to enter the brain. Therefore, one objective of this study is to examine whether autoantibodies enhance permeability of the human BBB. We will also test whether compounds that promote BBB repair, also prevent transport of autoantibodies across the BBB. This proposal has the potential to establish a new mechanism by which PANDAS autoantibodies cross the BBB and develop therapies for the disease.
Sleep and Circadian Disturbances as a Vulnerability for OCD
Kiara Timpano, PhD
University of Miami, Miami, FL
Award Amount: $45,989
Despite growing research, much regarding risk for OCD remains unknown. As a basic human need, sleep and circadian rhythms are a potential factor that may be important to consider as a vulnerability for OCD. Insomnia and related sleep impairments have been shown to have profound negative consequences on daily functioning and psychological difficulties. Preliminary work by our group and others has suggested that insomnia and delayed sleep may be linked with OCD. The proposed project is positioned to answer key questions and will address important limitations of past research. The overarching aim of our study is to conduct a multi-method investigation — including subjective, objective, and biological indicators — of sleep and circadian disturbances in relation to OCD. We plan to establish whether insomnia and delayed sleep are uniquely related to OCD compared to healthy controls and those with Hoarding Disorder. We also plan to examine the specificity of identified relationship, by taking symptoms of depression into account, and will furthermore consider how sleep deficits may exacerbate existing core cognitive features of OCD. Our findings will contribute meaningfully to current OCD vulnerability models and may also shed light on potential treatment implications.
MRS Glutamate-Stratified Treatment of Pediatric OCD
Erika Nurmi, MD, PhD
University of California, Los Angeles, School of Medicine
Award Amount: $49,989
Although effective treatments exist for obsessive-compulsive disorder (OCD), most patients experience only partial recovery and many fail to respond adequately at all, negatively impacting public health through increased morbidity and patient care expenses. Through our recent work, we have identified a brain-based biomarker of non-response to cognitive-behavior therapy (CBT) in youth with OCD, the recommended initial treatment for this disorder. This proposal aims to test a personalized treatment approach where youth with the biomarker will receive CBT augmented with a medication hypothesized to reduce its impact and lead to enhanced treatment outcomes.
In vivo identification of antibody targets in PANDAS/PANS
Luciana Frick, PhD
Award Amount: $49,277
Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) often strike in childhood and can disrupt the course of normal development. Acute onset of OCD and tics has been associated with recent infection with β-hemolytic streptococcus or other infectious diseases and has been hypothesized to result from autoantibodies that cross-react with brain proteins; this has been termed ‘pediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS) or ‘pediatric acute-onset neuropsychiatric syndrome’ (PANS). Therapies aimed at purging autoantibodies, like intravenous immunoglobulin (IVIG), have shown promise, but the nature of the autoantibodies remains obscure. Pathological changes in PANDAS/PANS have been documented in the basal ganglia, a network of nuclei deep within the forebrain, which has long been associated with OCD and TS. Sera from PANDAS patients have been shown to cross-react with human caudate, a component of this system. However, the basal ganglia are cellularly heterogeneous; ex vivo studies have not identified which specific cells are targeted by antibodies in PANDAS/PANS serum. We have developed a novel in vivo approach in mice to achieve this specificity. We will determine the differential binding of PANDAS/PANS serum from an NIMH/Yale clinical trial to different types of neurons after in vivo infusion into the striatum of transgenic mice, and whether IVIG treatment prevents this binding correlating with clinical improvement in patients.
Targeted Real-time NIRS-driven Neurofeedback: A Novel Treatment for OCD
Benjamin Kelmendi, MD
Yale University School of Medicine, Department of Psychiatry
Award Amount: $47,890
A quarter of patients with OCD receive little benefit from established treatments, and remission is rare. The development of new noninvasive treatments is an urgent clinical need. We have developed real-time fMRI neurofeedback targeting the orbitofrontal cortex (OFC), which has consistently been found to be hyperactive in OCD. We measure OFC activity using fMRI and present it to subjects as a visual feedback signal in real time. Subjects learn through trial and error to control their OFC. In published work, we have shown that this is efficacious in moderating both contamination anxiety in subclinically anxious individuals and symptom severity in patients with OCD, and to lead to lasting changes in brain functional organization. A recently funded R01 grant will support a sham-controlled study to test the efficacy of this intervention in patients. We are optimistic that this will prove to be a significant advance in the nonpharmacological treatment. However, even if efficacy is proven, this fMRI-based approach is likely to have limited impact, for practical reasons: it requires many hours of costly fMRI time in a highly specialized setting. Here we propose to adapt the neurofeedback strategy to be more generalizable, using near-infrared spectroscopy (NIRS). If therapeutic neurofeedback can be realized using NIRS, it would have enormous potential to become a generalized office-based treatment and to benefit many patients with refractory OCD.
Extinction as a Facilitator of Cognitive Bias Modification in Pediatric OCD
Michelle Rozenman, PhD
Post-Doctoral Research Fellow
UCLA Semel Institute for Neuroscience & Human Behavior
Award Amount: $49,197
A significant number of youths with OCD do not respond to evidence-based treatments. As a result, experts have called for new interventions that may directly target mechanisms underlying OCD. Cognitive Bias Modification for Interpretation biases (CBM-I) may be one such approach. CBM-I is a computerized intervention that helps individuals change their thinking patterns by training them to interpret ambiguous (unclear) information in a neutral, rather than threatening, manner; this change in thinking patterns may lead to reduction of OCD symptoms. CBM-I has not yet been tested as a potential intervention for pediatric OCD. The current study will test whether CBM-I reduces OCD symptoms in youth and how the intervention might work to change thinking patterns. Youths ages 10 to 17 (N=40) with high levels of OCD symptoms will be randomly assigned to 4 weeks (12 sessions) of either a personalized CBM-I program or a computerized control condition. At pre-, mid-, and post-treatment assessments, OCD symptoms and interpretation biases (i.e., how youths interpret ambiguous or unclear information) will be assessed. In addition, physiological arousal (heart rate, skin conductance, respiration) will be assessed during both a fear paradigm and behavioral approach tasks to examine whether extinction learning (a decline in fear-related behavior after learning new thinking patterns) is a mechanism underlying CBM-I. Should findings indicate that CBM-I works by extinction learning of fearful thinking, then the intervention might be particularly helpful before beginning exposure-based therapy. This study is innovative and has important clinical applications in its approach to testing CBM-I as a potential intervention for pediatric OCD.
Defining the Prevalence, Impacts, and Risk Factors of Hoarding Disorder
Ashley Nordsletten, PhD
Fellow Karolinska Institutet
Award Amount: $49,918
Hoarding Disorder (HD), a newly recognized psychiatric diagnosis, is characterized by a profound inability to get rid of one’s possessions, resulting in dangerous amounts of clutter throughout the sufferer’s home. Individuals with HD are often highly impaired, with symptoms affecting even basic day-to-day activities (e.g., cooking, bathing). Issues with poor sanitation, meanwhile, can pose broader health risks for the community. In addition, when legal interventions are used (e.g., forced cleanouts, evictions), these tend to generate large costs for society. Despite these widespread impacts, research focused on this newly acknowledged disorder is still in the beginning stages. In the absence of large-scale research, basic questions remain about the true prevalence, associated risk factors, and social/health consequences of HD. In response, we propose a research program with four goals: 1) To determine the prevalence of HD in a national sample; 2) to clarify the relationship between object hoarding, excessive acquisition, animal hoarding, and squalor at the population level; 3) to identify the social and medical consequences of HD using population databases only available in Sweden; and 4) to estimate the contribution of genetic as well as non-shared environmental risk factors in the possible causes of hoarding difficulties and excessive acquisition in two large groups of twins.
Effect of Intranasal Oxytocin on Social Cognition in Body Dysmorphic Disorder
Angela Fang, MA
Clinical Fellow in Psychology/Psychiatry, Massachusetts General Hospital/Harvard Medical School
Award Amount: $31,476
Despite the development of effective medication- and psychological-based treatments for body dysmorphic disorder (BDD), treatment outcome data suggest that there is still a lot of room for improvement. A closer examination of the biology associated with BDD may help uncover areas to target during interventions, and thus provide another approach to treatment. Oxytocin (a hormone) has been shown to be involved in the regulation of emotion recognition and social attentional processing. It is possible that oxytocin levels play a role in the development of these difficulties among individuals with BDD. The current study therefore aims to examine the effect of oxytocin administration on social cognitive impairments in BDD and OCD. Twenty treatment-seeking males in outpatient treatment with BDD, 20 individuals with OCD, and 20 participants with no BDD or OCD diagnosis will be assigned to receive an oxytocin and placebo nasal spray one week apart. During each visit, subjects will complete the Reading the Mind in the Eyes Test (which assesses emotion recognition) and the Trust Game (which assesses trust behavior) to measure oxytocin’s effect on each behavior. Importantly, our findings may show that a single administration of oxytocin may alter social cognitive processes thought to maintain BDD, and ultimately inform treatments for BDD.
Stepped Care CBT for Pediatric OCD
Adam Lewin, PhD
Assistant Professor, University of Southern Florida
Award Amount: $43,838
We are proposing a pilot study to develop and assess the feasibility and preliminary efficacy of Stepped Care cognitive-behavioral therapy for the treatment of pediatric obsessive compulsive disorder. This study represents an innovative approach to tailoring treatment to each child and family’s needs by developing a less costly, lower intensity intervention as a first step of treatment and “stepping-up” care for those patients requiring more intensive, personalized care. Without accessible and effective treatment, youth with OCD are at risk for a developmental trajectory of impairment and chronic distress that places undue burden on the child and family, and imposes significant societal costs. In line with the NIMH strategic plan that recognizes that “we are increasingly challenged by the costs and complexities of health care” and with the NIMH mission “to support research that optimizes services,” this project has the potential to empirically support the use of an innovative treatment that could be delivered with less therapist time, thereby reducing the cost of treatment for both patients and providers; improving treatment access; and reducing the societal impact and morbidity of childhood OCD.
Cognitive Biases in OCD: Mechanisms of Generational Transmission
Noah C. Berman, MA
Doctoral Student, Massachusetts General Hospital
Award Amount: $29,661
Cognitive biases (i.e., ways in which threatening information is processed) are recognized as distinct psychological diatheses for OCD. Thus, identifying the factors that contribute to OC-related cognitive biases will help tailor prevention and intervention programs to meet the individual needs of those who carry specific and measurable risk factors. No research, however, has empirically investigated the risk factors that predict attention and interpretation cognitive biases in youth at risk of developing OCD. The current study, therefore, will administer validated and age-appropriate self-report and idiographic behavioral measures to a well-characterized (i.e., diagnostically assessed) sample that is vulnerable to the development of OC-related cognitive biases — the offspring of a parent with OCD. We aim to better understand the complex interactional processes associated with offspring’s cognitive biases in order to improve the early detection and prevention of OC symptoms.
Replication of Genome-wide Association Findings of OCD
James A. Knowles, MD, PhD
Professor of Psychiatry, University of Southern California
Award Amount: $43,629
The International OCD Foundation Genetics Collaborative, a multi-national group established to discover genetic variation predisposing to OCD, has conducted the most extensive genetic study of OCD to date (half a million chromosomal locations in 1,465 affected individuals, 5,557 ancestry-matched controls, and 400 trios). Genome-wide significant evidence of association was found in the trios on chromosome 20 (rs6131295) near the gene encoding transcription factor BTBD3, but this finding was not significant when combined with the case-control data. Interestingly, the best results from this combined analysis were in genes (FAIM2 and ADCY8) with human brain expression patterns that are highly correlated with genes regulated by rs6131295 (BTBD3, DHRS11 and ISM1). This suggests an interrelated set of genes that may predispose individuals to OCD. We want to extend these initial GWAS findings by adding at least 1,348 OCD-affected individuals and 1,349 ancestry-matched controls to unequivocally identify a genetic locus (gene) for OCD and to provide a set of molecular targets for rational development of small molecule therapeutics for OCD.
The Role of Deep Brain Stimulation on Excessive Avoidance in Rats: A Mechanistic Window to Therapeutic Action in OCD
Tomek (Tomasz) Banasikowski, PhD
Post-Doctoral Fellow, University of Pittsburg
Award Amount: $40,000
Research using animal models of avoidance learning and extinction is changing the way we think about the etiology and treatment of anxiety disorders such as obsessive compulsive disorder (OCD). OCD is characterized by inflexible, repetitive behavior that is elicited by environmental stimuli to which the action has become strongly tied. According to the DSM-IV-TR, repetitive behaviors in OCD are perceived as “reducing distress or preventing some dreaded event” and are disruptive to a person’s social relationships and general everyday functioning. Recently, deep brain stimulation (DBS), a neurosurgical technique where high-frequency electrical impulses are applied to a specific brain region called the ventral striatum, has been shown to have potential therapeutic effect in treating refractory OCD symptoms in humans. However, little is known about DBS and how it affects the brain and its impact on behavior, emphasizing the need for translational animal studies. The proposed studies will examine the role of DBS, using a novel animal model of acquired avoidance. We will test an overarching hypothesis that DBS gradually disrupts excessive avoidance behavior by reducing the value and salience of anxiety-triggering stimuli i.e., environmental stimuli previously associated with aversive footshock. Concurrently, by recording electrical activity from brain regions implicated in compulsive behavior we will be able to examine DBS effects on a brain circuit-level in freely-behaving animals. The results from our studies will have a significant impact on understanding i) the neuronal mechanisms involved in compulsivity and its extinction, especially related to anxiety and avoidance reported in OCD, ii) system-level changes in response to DBS and iii) how such activation leads to adaptive behavior.
Investigation of Visual Perceptual Deficits in BDD using EEG
Doctoral student, University of California – Los Angeles
Award Amount: $40,079
Body dysmorphic disorder (BDD) is an obsessive-compulsive related disorder. Those with BDD are consumed with what they see as defects in the way they look, defects that are not noticeable or slight to others. Previous studies in BDD using functional magnetic resonance imaging (fMRI) suggest that how individuals with BDD process visual information might be different and that this difference in processing may cause these distortions (“I look unattractive because of these imperfections I see in my skin”). Our study will use electroencephalography (EEG) on the brains of those with BDD to look at the early visual response to faces, houses, and inverted faces. We will then compare the results to the results of those without BDD (controls) to see whether these distortions are a result of how the visual centers in the brain are working or due to differences in attention. This will help us better understand our earlier fMRI results as well as serve as the first EEG investigation on visual processing in BDD.
Comparison of Brain Activation Patterns in Hoarding Disorder and Non-Hoarding OCD
Carol A. Matthews, MD
Associate Professor, University of California – San Francisco
Award Amount: $49,928
This proposal will use functional MRI (fMRI) neuroimaging methods to examine brain activation patterns in Hoarding Disorder (HD) compared to Non-Hoarding Obsessive Compulsive Disorder (OCD) and healthy matched controls. Compulsive hoarding is currently classified as a subtype of OCD. However, severe compulsive hoarding will soon be categorized as an independent classification under the name Hoarding Disorder (HD), in part because of evidence that although there is overlap with OCD, hoarding disorder has separate genetic causes and different outcomes. Our group has evidence to suggest that people with HD have specific abnormalities in how they process information that differ from those seen in OCD. This study will extend our early work to compare the brain activation patterns of individuals with HD to those with OCD and to identify areas of overlap and areas of separation, eventually allowing for more targeted treatments and other interventions.
Stress Reactivity as a Mechanism of Treatment Response in Pediatric OCD
Tara Peris, PhD
Assistant Professor, UCLA Semel Institute
Award Amount: $49,580
Families of youth with OCD are characterized by an array of stressful family dynamics that predict poor response to cognitive behavior therapy (CBT), the current treatment of choice for pediatric OCD. However, understanding of the specific mechanisms which family functioning interferes with treatment is limited. Youth in unstable home environments have been found to exhibit prolonged activation of stress response systems, and separate research links this heightened reactivity to disrupted learning and the maintenance of fear/avoidance behaviors. Thus, one possibility is that poor family functioning complicates CBT via heightened stress reactivity. Employing a multi-method battery, this study examines parent and child stress reactivity over the course of CBT with the goal of understanding how the pathophysiology of pediatric OCD changes with treatment; how parent and child stress reactivity relate to ability to complete key CBT tasks; and their role in CBT outcome.
Combining Acceptance and Commitment Therapy with Exposure and Response Prevention to Enhance Treatment Engagement
Michael Twohig, PhD
Assistant Professor, Utah State University
Award Amount $50,344
The goal of this proposal is to increase the acceptability and client engagement in Exposure with Response Prevention (ERP). Recent research has shown that Acceptance and Commitment Therapy (ACT), without in-session exposure, is an effective treatment for OCD, and it has high acceptability and low refusal and drop-out rates. Research has also shown that procedures taken from ACT can increase engagement in exposures for anxiety disorders. Still, the most logical way for ACT to be implemented for OCD is within an exposure framework. Based on past research, it appears that conducing ACT within an ERP framework should result in high levels of treatment engagement and high acceptability. This study will treat 60 adults with ACT using either traditional ERP or ACT+ERP. Investigators will look at levels of treatment engagement (i.e., number of exposures, how well were exposures attempted, how much response prevention occurred?), and acceptability. If treatment engagement and acceptability can be increased, it is likely that greater improvement could be seen in OCD reduction in a larger study. This is a collaborative cross-site study with leading ACT (Dr. Twohig) and ERP (Dr. Abramowitz) researchers.
Internet-delivered EX/RP for early-onset OCD — A pilot feasibility trial
Jonathan S Comer, PhD
Co-Director of Research Child Program, Boston University Center for Anxiety and Related Disorders
Award Amount $38,600
Early-onset OCD (i.e., onset < 9 years) has been observed, with earlier onset associated with a more complex and intractable course in adulthood. Earlier onset symptoms exhibit considerable stability, are associated with profound disability, and confer sizable risk for later life psychopathology and reduced quality of life. Effective early intervention is critical, although, despite progress in supported programs, gaps persist between treatment in experimental settings and services available in the community. Inadequate numbers of professionals trained in evidence-based programs impinge on availability of care. Cost and transportation issues further constrain access. Youth from low-income or remote communities are particularly unlikely to receive effective treatments. Technological innovations can overcome traditional barriers to care. In the treatment of early OCD, such innovative methods may overcome geographical barriers to care by extending the availability of expert services and addressing regional workforce shortages in care. Families dwelling in underserved regions can participate in real-time treatment conducted by experts, regardless of geographic proximity to an expert OCD clinic. Treating families in their natural settings can overcome issues of space, transportation, and convenience that traditionally hinder treatment accessibility. Moreover, delivering treatment directly to families in their homes may extend treatment relevance, as treatments are delivered in the very context in which many symptoms occur. Given support for CBT for early OCD, establishing the feasibility and preliminary efficacy of an Internet format is a critical step in the evaluation of new technologies and their potential for offsetting the debilitating course of early OCD. The present objective is to develop a real-time, Internet-delivered treatment protocol for early onset OCD in youth ages 4-8, and to evaluate via randomized design the feasibility, acceptability, and preliminary efficacy of enrolling, retaining, and treating children with the modified format relative to those treated with in-office family-based treatment for early childhood OCD.
The Frequency of Oscillations in Obsessive-Compulsive Disorder
Elana Harris, MD, PhD
Assistant Professor, Cincinnati Children’s Hospital Medical Center
Award Amount: $50,000
Obsessive Compulsive Disorder (OCD) is a debilitating neuropsychiatric disorder with a lifetime prevalence of up to 3% in the general population. Aberrant circuitry within cortical-striatal-thalamic-cortical loops has been widely hypothesized to underlie the symptoms of OCD, but our understanding of the pathophysiology of OCD and communication among these structures has been hampered by temporal limitations of imaging modalities. We intend to use magnetoencephalography (MEG) and advanced signal analysis to complement prior functional Magnetic Resonance Imaging (fMRI) studies of OCD. Recordings will be made while healthy subjects and subjects with OCD view blocks of neutral and symptom-provocative images. We will track the time of activation and detect differences in the relative power of frequency bandwidths when we compare patients with healthy subjects. This will allow us to follow the spread of neuronal activity in patients with OCD. Our findings may guide the design of future treatments by indicating the location and frequency at which to stimulate brain regions with transcranial magnetic stimulation.
Thank you to our 2020 Grant Review Committee:
- Christopher Pittenger, MD, PhD, Chair - Yale University
- Jennifer Freeman, PhD, Vice Chair - Brown University
- Jonathan Abramowitz, PhD - UNC Chapel Hill
- Thomas Adams, PhD - University of Kentucky
- Dritan Agalliu, PhD - Columbia University
- Susanne Ahmari, MD, PhD - University of Pittsburgh
- Paul Arnold, MD, PhD - University of Calgary
- Kristen Benito, PhD - Brown University
- Noah Berman, PhD - Massachusetts General Hospital/Harvard Medical School
- Michael Bloch, MD - Yale University
- Brian Brennan, MD - McLean Hospital/Harvard Medical School
- Joan Camprodon, MD, PhD - Massachusetts General Hospital/Harvard Medical School
- Christine Conelea, PhD - University of Minnesota
- Lisa Coyne, PhD - Harvard University
- Darin Dougherty, MD - Massachusetts General Hospital/Harvard Medical School
- Ann-Christine Ehlis, PhD - University of Tübingen
- Thomas Fernandez, MD - Yale University
- Lorena Fernández de la Cruz, PhD - Karolinska Institutet
- Jamie Feusner, MD - University of California Los Angeles
- Martijn Figee, MD - Mount Sinai School of Medicine
- Sarah Fineberg, MD, PhD - Yale University
- Christopher Flessner, PhD - Kent State
- Marty Franklin, PhD - Rogers Behavioral Health
- Jennifer Frankovich, MD - Stanford University
- Randy Frost, PhD - Smith College
- Sarah Garnaat, PhD - Brown University
- Dan Geller, MD - Massachusetts General Hospital/Harvard Medical School
- Lizabeth Goldstein, PhD - US Veterans Administration
- Wayne Goodman, MD - Baylor College of Medicine
- Jon Grant, MD - University of Chicago
- Dorothy Grice, MD - Mount Sinai School of Medicine
- Patricia Gruner, PhD - Yale School of Medicine
- Nouchine Hadjikhani, MD, PhD - Massachusetts General Hospital/Harvard Medical School
- Mady Hornig, MD - Columbia University
- Benjamin Kelmendi, MD - Yale University
- Joshua Kemp, PhD - Brown University
- Silvia Kober, PhD - University of Graz
- James Leckman, MD - Yale University
- Simone Macri, PhD - Instituto Superiore di Sanità
- Rachel Marsh, PhD - Columbia University
- David Mataix-Cols, PhD - Karolinska Institutet
- Carol Mathews, MD - University of Florida
- Joseph McGuire, PhD - Johns Hopkins
- Nicole McLaughlin, PhD - Brown University
- Jeff Meyer, MD, PhD - Centre for Addiction and Mental Health
- Moh Milad, PhD - New York University
- Kirsten Müller-Vahl, MD - Hannover Medical School
- Jordana Muroff, PhD - Boston University
- Melissa Norberg, PhD - Macquarie University
- Ed Pace-Schott, PhD - Massachusetts General Hospital/Harvard Medical School
- Michele Pato, MD - SUNY
- Tara Peris, PhD - University of California Los Angeles
- Noah Philip, MD - Brown University
- John Piacentini, PhD - University of California Los Angeles
- Helen Pushkarskaya, PhD - Yale University
- Bradley Riemann, PhD - Rogers Behavioral Health
- Susan Rossell, PhD - Swinburne University
- Katherine Scangos, MD, PhD - University of California San Francisco
- Brad Schmidt, PhD - Florida State University
- Gail Steketee, PhD - Boston University
- Emily Stern, PhD - New York University
- S. Evelyn Stewart, MD - University of British Columbia
- Eric Storch, PhD - Baylor College of Medicine
- Henry Szechtman, PhD - McMaster University
- Steven Taylor, PhD - University of British Columbia
- Margo Thienemann, MD - Stanford University
- David Tolin, PhD - Hartford Hospital
- Michael Twohig, PhD - Utah State University
- Barbara Van Noppen, PhD - University of Southern California
- Valerie Voon, PhD - Cambridge University
- Michael Wheaton, PhD - Barnard College
- Alik Widge, MD, PhD - University of Minnesota
- Kyle Williams, MD, PhD - Massachusetts General Hospital/Harvard Medical School
- Monnica Williams, PhD - University of Ottawa
- Bethany Wootton, PhD - University of Technology Sydney
- Brian Zaboski, PhD - Yale University