The Research Grant Recipients Archive describes studies that were funded by the IOCDF and its predecessor, the Obsessive Compulsive Foundation (OCF), since 1994. We are working to provide the most up-to-date information about these studies, with the collaboration of the researchers who have conducted the research presented here. While some entries are complete with descriptions and resulting publications, updating others is a work in progress as we get the latest details.
For more information about any of the studies presented in our Archive, please email email@example.com.
Research is vital to our goals of increasing our understanding of OCD and related disorders, improving treatment, and reducing stigma. 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 $10.6 million in research grants, and continues to offer research grant awards annually. As of 2022, there are three grants available: the Breakthrough Award, the Innovator Award, and the Michael A. Jenike Young Investigator Award.
Since 2018, Breakthrough Awards are awarded to investigators whose work represents “high-risk, high-reward” science that could make a profound impact in the field of OCD and related disorders. The goal of the Breakthrough Awards is to accelerate progress toward new and more effective treatments for OCD, leading us closer to a cure. These Awards are made possible through the generosity of anonymous donors.
Since 2019, the Innovator Award is awarded to an investigator whose work focuses on the ultimate goal of finding a cure for OCD and related disorders. In 2022, researchers submitted proposals to explore a special focus: the relationship between co-occurring OCD and bipolar disorder. Bipolar disorder is a serious mental health condition marked by depressive and manic episodes, whose interaction with OCD can lead to a worsening of symptoms and quality of life. By exploring the underlying mechanisms and causes of co-occurring OCD and bipolar disorder, the awardee will advance our understanding and contribute to the development of more effective treatments for both conditions. This Award is typically made possible through the generosity of an anonymous donor, but has been funded by the Walder Family Charitable Fund in 2022.
Michael A. Jenike Young Investigator Awards
Since 2018, the Michael A. Jenike Young Investigator Award has funded promising early-career researchers who are working to establish themselves in the field of OCD and related disorders. Funding for Young Investigator Awards is allocated towards several specific topics each year, such as body dysmorphic disorder; the role of race, ethnicity, and culture in OCD and related disorders; and PANDAS/PANS. These Awards are made possible through the generosity of thousands of individual donors who contribute to the IOCDF Research Grant Fund every year. In 2022, PANDAS Network funded two Young Investigator Awards that focused on PANDAS/PANS.
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).
2022 Research Grant Awardees
We are excited to announce the 2022 IOCDF Research Grant awardees! We awarded $1.6 million in funding to researchers pursuing exciting and impactful projects on a range of topics in OCD and related disorders including PANDAS/PANS. To read more about their projects, click "2022 IOCDF Research Grant Award Winners" below!
These nine winning grants were selected through a rigorous and highly competitive peer-review process, where a panel of 74 top researchers was asked to review grants in their areas of expertise. The $300,000 Innovator Award for OCD and bipolar disorder research was funded by a partnership with the Walder Family Charitable Fund. Two Young Investigator grants totaling $100,000 for PANDAS/PANS research were funded by a partnership with PANDAS Network. The most highly rated projects in the first round were then subjected to a second round of scrutiny from the full committee. The final nine projects represent the strongest and most promising science from an excellent pool of applications.
Innovator Award Recipient
Dissecting the Temporal and Causal Relationships between OCD and Bipolar Disorder
Principal Investigator: Dorothy Grice, MD
Icahn School of Medicine at Mount Sinai (New York, NY)
Award Amount: $300,000 (funded by the Walder Family Charitable Fund)
Compared to the general population, people with OCD are 10 times more likely to have a bipolar disorder (BPD) diagnosis. Research has shown that BPD comorbidity is associated with more severe OCD, and worse health and quality of life outcomes. Treatment for people with both conditions also differs from standard OCD treatments to account for BPD symptoms. As a first diagnosis of OCD is associated with a higher risk of a later diagnosis of BPD, understanding the causes behind co-occurring OCD and BPD is necessary. These causes may be shared genetic and/or environmental risk factors that increase the chance of both conditions occurring, and/or causal relationships where one disorder increases the likelihood of the other. Using a large national demographic and clinical dataset and large-scale genetic studies, this study aims to explore shared genetic and environmental risk between OCD and BPD, and assess whether OCD increases the likelihood of BPD. With these findings, the study will develop models to predict a future BPD diagnosis in people with OCD.
Breakthrough Award Recipients
Neural Mechanisms of Active Avoidance in Obsessive Compulsive Disorder
Principal Investigators: Emily Stern, PhD & Mohammed R. Milad, PhD
Nathan Kline Institute for Psychiatric Research/Research Foundation for Mental Hygiene (Orangeburg, NY)
Award Amount: $500,000
According to behavioral models of OCD, compulsions are avoidance behaviors that alleviate distress from obsessions in the short term. Over time, this reinforces beliefs that obsessions are intolerable and that these compulsions must be performed to bring relief. One of the core aspects and main benefits of ERP is eliminating these avoidance behaviors – yet we still do not understand exactly how the brains of people with OCD work as these behaviors unfold. This study will use neuroimaging techniques and an avoidance learning task to learn what happens in the brain during avoidance behaviors in 60 people with OCD and 60 people in a control group. As people with OCD have a wide range of symptoms, it will also look at how brain function during avoidance is associated with this variability of symptoms. By looking at the neural correlates of avoidance behaviors in OCD, this study aims to provide new directions for existing treatments and potentially lead to new interventions.
CBT Augmentation to Promote Medication Discontinuation in Pediatric OCD
Principal Investigator: Eric Storch, PhD
Baylor College of Medicine (Houston, TX)
Award Amount: $499,891
Several treatments have shown efficacy for treating pediatric OCD: cognitive behavioral therapy (CBT), medication with a serotonin reuptake inhibitor (SRI), and their combination (SRI+CBT). Although best practice suggests using CBT to treat children with mild-to-moderate OCD, SRIs are still typically prescribed first regardless of severity – even though they have modest therapeutic effects, a range of serious side effects, and potentially damaging outcomes. An adult trial demonstrated that gradual SRI discontinuation resulted in noninferior outcomes relative to SRI continuation across 24 months of follow-up after SRI+CBT, suggesting that SRI treatment can be safely discontinued with the help of CBT. This study will examine SRI tapering for 141 children with at least moderate OCD receiving CBT across 24 weeks of follow-up, to assess whether this will reduce OCD symptoms and ultimately lead to successful SRI discontinuation. These results will be used to inform policy and practice regarding maximizing outcomes among children, lessening exposure to unnecessary treatments, and returning youth to everyday living. Beyond pediatric OCD, this project hopes to serve as a possible model for other conditions, such as anxiety disorders.
Michael A. Jenike Young Investigator Award Recipients
Expanding the Genetic Landscape of Pediatric OCD
Principal Investigator: Emily Olfson, MD, PhD
Yale School of Medicine (New Haven, CT)
Award Amount: $49,993
While the role of genetic factors in the development of OCD has been emphasized through research, more attention is needed to identify specific risk factors and underlying biological pathways. Past OCD genomic studies focused on single categories of genetic variation, but data suggests that a combination of genetic changes may impact an individual’s likelihood of developing OCD. Past genomic studies in OCD have a vast variety of factors, yet these all require different analysis techniques. This study will examine rare, common, sequence, and structural genetic variations simultaneously within the same individuals with OCD using a sample of 200 family trios. With the help of a whole-exome DNA sequencing study of families where the child has a primary OCD diagnosis that demonstrated the role of rare sequence variation, this study will add genome-wide array data to examine the role of rare and common variants. Additionally, the data from these 200 families will be combined with a separate cohort of 200 families with body-focused repetitive behavior diagnoses to examine genetic factors that are shared and distinct across the OCD spectrum. By integrating different categories of genetic variation, this study aims to advance our understanding of the genomic landscape of pediatric OCD and related conditions, provide insight into how variants impact risk of developing OCD, and inform future interventions.
Improving Access to Evidence-based Interventions for Adolescents with Body Dysmorphic Disorder
Principal Investigator: Daniel Rautio, Msc, PhD Candidate
Karolinska Institutet (Solna, Sweden)
Award Amount: $49,750
Body dysmorphic disorder (BDD) is a common and impairing disorder that typically onsets before the age of 18. Although cognitive behavioral therapy (CBT) can effectively prevent severe long-term consequences of BDD if applied at an early age, it is scarcely available. To address this gap, Internet-delivered CBT (ICBT) was developed as a form of guided self-help, and was shown to be an effective treatment for adults with BDD. A pilot study by the authors of this project that assesses ICBT for adolescents with BDD is also showing promising treatment effects. This study will expand the pilot into a randomized controlled trial to test ICBT’s efficacy on 136 adolescents with BDD over the course of 14 weeks, compared to an Internet-based supportive therapy control. It will assess ICBT’s effects on BDD symptom severity, how well participants respond to treatment, and cost-effectiveness of the application. By examining these factors, this study hopes to show that evidence-based treatment for young people with BDD is effective – and available.
Perinatal Obsessive Compulsive Disorder: A Person-centered, Dynamic Systems Approach
Principal Investigator: Samantha Hellberg, MA
University of North Carolina at Chapel Hill (Chapel Hill, NC)
Award Amount: $49,566
1 in 5 parents experience perinatal distress (PND), significant mental health challenges that impact their – and their children’s and families’ – lives and wellbeing. While perinatal mood and anxiety disorders (PMADs) have received increasing attention, more research on perinatal OCD (pOCD) is needed. Although symptoms vary from person to person, individuals with pOCD often have highly distressing thoughts surrounding the safety and wellness of their children, and engage in compulsive behaviors to try to reduce the resulting distress. Individual differences in how PND is experienced pose a major obstacle to understanding, preventing, and treating pOCD effectively. Ambulatory assessment (AA) may offer novel opportunities to examine individual pOCD experiences in real-world settings, but no studies have used AA to examine pPOCD. This study aims to address this research gap by using smartphone-based longitudinal AA to assess 66 pregnant individuals at high risk for PND during late pregnancy and the first postpartum months. By looking at associations among symptoms and relevant events and feelings in real time, this study will probe into the individual differences, onset, and progression of pOCD presentations. Through the context-aware, time-sensitive, and person-specific inferences about pOCD, this research into AA can inform future personalized interventions for parents at a critical stage.
Examining Circadian and Non-circadian Phenotypes in Obsessive Compulsive Disorder with Delayed Bedtimes
Principal Investigator: Rebecca Cox, PhD
University of Colorado, Boulder (Boulder, CO)
Award Amount: $49,933
Relapse rates following OCD treatment are 50%, suggesting the existence of unidentified and untreated mechanisms in OCD. One of these mechanisms relates to circadian rhythm – the body’s biological clock. One indicator of circadian rhythms is sleep timing, and previous research has found that people with OCD tend to have later sleep timing (going to bed and waking up later), which is associated with worse OCD symptoms. However, it is still unclear whether later sleep timing in OCD is due to a delayed circadian rhythm or non-circadian factors such as staying up later engaging in compulsions. This study will clarify the role of circadian rhythms in later sleep timing in OCD by measuring the associations between the timing of melatonin, desired bedtime in adults with OCD, and later sleep timing. The findings will provide important insight into whether circadian rhythms could be a new target for OCD treatment.
A Modifiable Transcriptomic Signature of Immune Dysfunction in Pediatric Obsessive Compulsive Disorder (OCD)
Primary Investigator: Shrujna Patel, PhD
Sydney Children’s Hospital Network (Sydney, Australia)
Award Amount: $50,000 (in partnership with PANDAS Network)
Research shows that many children with PANS have dysfunctional immune systems. When conventional psychiatric medications fail, treatments such as intravenous immunoglobulin (IVIG) have shown some success; however, IVIG is short-term, costly, and invasive. Further research into such treatments is impeded by lack of knowledge about PANS biomarkers. Using RNA sequencing of whole blood, this team identified a transcriptomic signature of immune dysfunction in children with PANS, whose features are modifiable with IVIG and associated with clinical improvements. This study aims to validate this signature in a larger cohort of children with PANS, examine it at a cellular level, and explore how IVIG modifies this signature at a cellular level. The results from this study will provide the first evidence for a signature of immune dysfunction in children with PANS, increasing our potential at finding effective treatments.
Elucidating the Role of RXRA Factor in Myeloid Cells for Immune-mediated Mechanisms of OCD
Primary Investigator: Uğur Akcan, PhD
Columbia University (New York, NY)
Award Amount: $50,000 (in partnership with PANDAS Network)
PANDAS may be associated with a form of basal ganglia encephalitis (BGE) caused by repetitive Group A Streptococcus (GAS) infections. Findings show that the immune response targeting repetitive GAS infections can lead to inflammation of the brain and nervous system. As not every child develops BGE, there may be a genetic component related to the development of PANDAS. This team has identified approximately 20 genes associated with BGE, one of which is Retinoid X Receptor Alpha (RXRɑ) – responsible for regulating innate and adaptive immune responses. Using imaging techniques on mice and humans, this study aims to assess the importance of RXRɑ for regulating the immune response of myeloid cells that can affect the nervous system following repetitive GAS infections. Additionally, it proposes to test the effects of RXRɑ loss in mouse myeloid cells to understand effects on the nervous system after these infections. These explorations may aid in developing potential biomarkers and therapeutics to assist in diagnostic and treatment strategies for PANDAS.
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 130 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:
Innovator Award Recipients
How Disease and Medication Shape the Brain, and How the Brain Predicts Individual Treatment Response; Learning from Global Collaboration
Principal Investigators: Odile van den Heuvel, MD, PhD; Chris Vriend, PhD
Amsterdam UMC (Amsterdam, The Netherlands)
Award Amount: $300,000.00
Category: Neuroscience, Treatment
Brain imaging has revolutionized our understanding of mental health disorders like OCD by revealing important information about which parts of the brain are impacted by OCD and informing treatment approaches. Research through brain imaging becomes more reliable through the availability of higher sample sizes, as they allow for greater confidence about minor differences observed between people with OCD and healthy people – minor differences that may have important meanings.
This study by Drs. van den Heuvel and Vriend will continue the ENIGMA-OCD collaborative working group’s brain imaging research, using data pooled from multiple institutions around the world to create a much larger sample of people with OCD than any one researcher would be able to study on their own. The working group has already discovered small changes in brain structure that may exist in people with OCD. This Award’s support will help the team look at new questions, such as: Does the length of time that a person has had OCD have an impact on brain function? How does medication for OCD alter brain function? And can differences in brain function observed using brain imaging technology predict how well a person will respond to OCD treatment? Currently the team is working on brain imaging data visualizing the brain’s function during emotional processing. In the next stage, they will focus on cognitive functions, such as inhibition of responses and higher order cognitive functions.
Pairing tVNS and Exposure and Response Prevention to Improve Symptoms of OCD
Principal Investigators: John Williamson, PhD; Carol Mathews, MD
University of Florida (Gainesville, FL)
Award Amount: $300,000.00
Category: Neuroscience, Treatment
Cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) is a safe, effective, and proven treatment for OCD. Some researchers believe that ERP’s efficacy lies behind helping patients “un-learn” the connection between compulsive behaviors and feelings of relief from anxiety or fear. If this process, called “fear extinction learning,” could be accelerated or enhanced during therapy, it may bring faster improvement in symptoms and relief to people with OCD.
Previous research has suggested that stimulating the vagus nerve – the nerve that connects the brain to the heart, lungs, and gut – could help enhance fear extinction learning. Advances in technology have made it possible to stimulate the vagus nerve through the skin without incisions, and with only limited discomfort to patients, making it possible for patients to receive vagus nerve stimulation and therapies like ERP at the same time. Based on their promising results in research about vagus nerve stimulation in patients with post-traumatic stress disorder (PTSD), this team aims to study vagus nerve stimulation in OCD. The results may lead to a better understanding of how ERP works to benefit patients, as well as create a new option to enhance its effectiveness.
Michael Jenike Young Investigator Award Recipients
Optimization of Parent-Led Exposure Delivery in Pediatric OCD
Principal Investigator: Erin O’Connor, PhD
Pediatric Anxiety Research Center at Bradley Hospital (Providence, RI)
Award Amount: $50,000.00
Category: Pediatric OCD, Treatment
When children develop OCD, the most effective treatment available for them is cognitive behavioral therapy (CBT) with exposure and response prevention (ERP). Children engage in exposure work where they intentionally trigger their fears (or engage in activities that are likely to trigger those fears) and prevent themselves from engaging in compulsive rituals meant to reduce or eliminate their anxiety. Most exposure work occurs outside of the therapist’s office, with parents often deeply involved in helping their children.
Dr. O’Connor and her team are training 30 parents in the essentials of ERP, and testing this training’s effectiveness. The hope is that, through this training, parents will become better equipped to guide their children through exposures at home, and will be able to help children engage in a greater quantity of high-quality exposures, leading to better treatment outcomes.
Developing a Cultural Adaptation Toolkit to Increase Equity for Underserved Youth with Obsessive-Compulsive and Related Disorders
Principal Investigator: Amanda Sanchez, PhD
University of Pennsylvania (Philadelphia, PA)
Award Amount: $50,000.00
Category: Race, Ethnicity, & Diversity
While many effective treatments for OCD have been developed through research, most of the studies used did not include diverse groups of research participants. This lack of diversity led to a gap in learning how treatments can be adapted to meet the unique needs of diverse populations. These needs can be influenced by many aspects of identity including race, ethnicity, culture, income, gender identity, sexual orientation, immigration status, and other socioeconomic and cultural factors—or their unique combinations.
To help clinicians adapt OCD treatments to meet the challenges of all clients, Dr. Sanchez and her team are collecting strategies utilized for adapting OCD treatment to meet the needs of low-income youth and youth of color. Through interviews with youth and clinicians, as well as data collected at a clinic serving youth of color and low-income youth in Philadelphia, they are creating a toolkit and training that will help clinicians overcome barriers and provide effective treatment to youth with OCD from a greater range of backgrounds. The toolkit development is underway with iterative feedback from advisory board members. To date, 28 participants have been interviewed, and recruitment is wrapping up. In addition, a survey for clinicians working with youth with anxiety and OCD will be deployed to assess the initial feasibility and acceptability of the toolkit.
Correlates of Treatment Outcome Using Multimodal Neuroimaging in Children with PANDAS
Principal Investigator: Sarah O’Dor, PhD
Massachusetts General Hospital/Harvard Medical School (Boston, MA)
Award Amount: $50,000.00
Category: PANDAS/PANS, Pediatric OCD, Neuroscience
Researchers are increasingly interested in the connection between inflammation in the brain and OCD symptoms in both Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) and more typical childhood-onset OCD. Previous research has found that naproxen sodium (brand name “Aleve”) can treat inflammation in the brain, and has helped alleviate OCD symptoms in children with PANDAS.
Dr. O’Dor and her team are investigating how naproxen sodium changes the brains of these children by using cutting-edge magnetic resonance imaging (MRI) techniques to measure inflammation. The project’s findings will provide additional data regarding the role of inflammation in childhood OCD, and may unlock new avenues for treatment.
Beyond the Goal versus Habit Binary: A Computational EEG Study of the Neurocognitive Mechanisms of Obsessive Compulsive Disorder
Principal Investigator: Amy Rapp, PhD
Columbia University (New York, NY)
Award Amount: $50,000.00
In order to better understand OCD, researchers are investigating what happens in the brain when people with OCD perform compulsions. Research shows that in OCD, the parts of the brain that allow us to control and regulate repetitive habits are not working right, leading to repetitive, ritualistic behaviors.
Dr. Rapp and her team are examining if differences in brain activity while people learn and make decisions are responsible for compulsive behaviors in OCD. They are collecting highly detailed information about brain function from 30 people with OCD and 30 healthy controls using electroencephalograms (EEG), which measure electrical activity in the brain using sensors in a cap that participants will wear on their heads. Ultimately, the project may provide a richer and fuller understanding of what happens in the brain during compulsions in OCD and provide new avenues for treatment and prevention. Initial results from this project were presented at the 2022 IOCDF Research Symposium in Denver.
Waxing and Waning: Using Ecological Momentary Assessment to Assess Chronotype as a Potential Mechanism of Within-Day Obsessive-Compulsive Disorder Symptom Fluctuations
Principal Investigator: Hadar Naftalovich, MA
Hebrew University of Jerusalem (Jerusalem, Israel)
Award Amount: $44,500.00
Category: Sleep and OCD
Prior research has suggested links between a person’s sleep habits, their biological clock (circadian rhythm), and OCD symptoms. Many people with OCD report that their symptoms are better or worse at certain times of day, and that they may struggle more with their OCD when they are tired. However, each person has a unique circadian rhythm (“chronotype”) that influences when they feel most alert; “morning people” feel energized early in the day, “night owls” feel energized at night, and others fall in between.
Ms. Naftalovich and her team are examining the links between chronotypes, levels of alertness, and OCD symptoms by closely tracking these factors and sleep patterns in a group of participants for a period of seven days. The goal is to gain a better understanding of how and why OCD symptoms fluctuate throughout the day, and to give people with OCD additional tools and information to understand when their symptoms may be the easiest or most difficult to control. Findings could provide clues about how treatments that influence alertness and circadian rhythm (like light therapy) could be combined with existing forms of OCD treatment to better serve patients.
Identifying targets for prevention and early intervention in Obsessive-Compulsive Disorder
Primary Investigator: David Mataix-Cols, PhD
Karolinska Institutet (Solna, Sweden)
Award Amount: $500,000.00
Category: Genetics, Pediatric OCD
Research has found that the risk for developing OCD is not only due to the genes we inherit from our parents, but also from environmental factors. However, it is unclear precisely which factors increase this risk, and by how much. By exploring how genetic and environmental factors interact further, it may be possible to ultimately diagnose and treat OCD earlier and faster.
Dr. Mataix-Cols and his team will recruit a large number of identical twin pairs (who share the same exact genes) where one twin has OCD and one does not – with the goal of understanding whether something in the environment led to OCD developing. The team will access a vast amount of early-life and medical information about these twin pairs using the unique Swedish nationwide registries. 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 team will then analyze this data to identify the environmental variables 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. As of November 2022, the team has recruited 18 pairs (36 individuals) of the target 50 pairs of discordant twins.
A Precision Medicine Approach to OCD Treatment: Targeting Neuroinflammation
Primary Investigator: Jeffrey Miller, MD
Research Foundation for Mental Hygiene, Inc./Columbia University (New York, NY)
Award Amount: $500,000.00
Category: Neuroinflammation, Neuroscience, Pharmacology
Much prior research has found evidence of brain inflammation’s role in the development of OCD. As a result, anti-inflammatory medications have been suggested as a potential avenue for treating symptoms in individuals with OCD.
Building off this early evidence, Dr. Miller and his team will test a new OCD treatment strategy by measuring and targeting inflammation in the brain. The team will precisely measure brain inflammation in a group of 21 people with OCD using PET imaging and blood sampling, and then provide them with treatment using the anti-inflammatory drug celecoxib (brand name “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. In addition, they are comparing measures of inflammation in the body and the brain between patients with OCD and healthy volunteers. 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. Recruitment is ongoing in this study.
Michael Jenike Young Investigator Awards
Using a Machine Learning Approach to Identify Immune Biomarkers Associated with PANS/PANDAS
Primary Investigator: Lauren Breithaupt, MD, PhD
Massachusetts General Hospital/Harvard Medical School (Boston, MA)
Award Amount: $50,000.00
Category: Genetics, Neuroinflammation, PANDAS/PANS, Pediatric OCD
Despite recent research into Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and Pediatric Autoimmune Neuropsychiatric Syndrome (PANS), clinicians and researchers often struggle to differentiate childhood OCD and PANDAS/PANS. These two conditions require different clinical treatment protocols, but there is no biological test to confirm that a child indeed does have PANDAS/PANS vs. OCD.
Dr. Breithaupt and her team 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. Their approach uses machine learning — a form of artificial intelligence — to sift through this large volume of data to find hidden patterns. The 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. Dr. Breithaupt and her team have recently completed the proteomics analysis of largest dataset of adolescent OCD, PANDAS, and ARFID, and are eager to present the results in 2023.
Understanding and treating OCD in older adults
Primary Investigator: Carly Johnco, PhD
Macquarie University (Sydney, Australia)
Award Amount: $50,000.00
With the population aging globally, the number of older adults with OCD is expected to double within the next 30 years. We currently lack important information about the best possible ways to treat this growing number of older adults, and how to modify approaches that work with children and adults to best serve this population.
Dr. Johnco’s project will focus on family accommodation (when a family member of a person with OCD helps that person with their rituals) for older adults with OCD. Accommodation in childhood and adult OCD is well understood, and treatment approaches now commonly involve family members to reduce these actions 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. This study will investigate the ways that accommodation plays a role in the lives of older adults with OCD, with the aim of developing a treatment protocol to address age-appropriate accommodation that considers the unique circumstances of aging with this disorder.
Intervening on Loneliness to Reduce Object Attachment in Hoarding Disorder: Two Randomized Controlled Pilot Studies
Primary Investigator: Keong Yap, DPsych
University of New South Wales (Sydney, Australia)
Award Amount: $48,000.00
Category: Hoarding disorder
People with hoarding disorder (HD) experience strong emotional attachment to their possessions, and extreme difficulty and distress when throwing things away. This can lead to excessive collecting of possessions, with risks to movement in one’s home, sanitation, and safety. One possible explanation for this strong emotional attachment to possessions is loneliness, as people with HD bond with their possessions to replace the bonds with other people that are missing from their lives. The social impacts of HD may reinforce and deepen these feelings of loneliness by making it difficult to form or sustain healthy relationships.
Dr. Yap and his team will attempt to address loneliness in people with HD through an online program that is known to be effective in reducing feelings of loneliness. The team has completed the first proof-of-concept study where they randomly assigned 298 people screened for high levels of hoarding symptoms to the Building Stronger Connections (BSC) program or to a control condition. The BSC program is an online psychoeducation program which presents facts and myths about loneliness. It also introduced strategies and activities to help participants reduce social isolation. The results showed that BSC led to a greater reduction in loneliness relative to controls, and that the reduction in loneliness was associated with a reduction in their emotional attachment to objects. The team is currently making improvements to the program based on participant feedback for their second study and plan to recruit clinical participants with HD in 2023.
Breakthrough Award Recipients
Clinical Trial of Image-Guided Low-Intensity Focused Ultrasound Pulsation (LIFUP) for the Treatment of Obsessive Compulsive Disorder (OCD)
Primary Investigators: Wayne Goodman, MD; Darin Dougherty, MD
Baylor College of Medicine (Houston, TX); Massachusetts General Hospital (Boston, MA)
Award Amount: $499,950.00
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 called low-intensity focused ultrasound pulsation (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. The results from the study could ultimately help people with treatment-resistant OCD access a non-invasive and effective treatment to manage their symptoms. The team expects to start enrollment of participants in early 2023.
Pilot Study of the Glutamate AMPAR Modulator RR-HNK in OCD
Primary Investigator: Carolyn Rodriguez, MD, PhD
Stanford University (Stanford, CA)
Award Amount: $498,393.00
Although there are medications that can help people with OCD manage their symptoms, those that are currently available may take up to two to three months to begin working. Additionally, these rarely relieve 100% of patients’ symptoms.
Dr. Rodriguez and her team are investigating new medications that could begin working faster and relieve OCD symptoms more completely. In a prior pilot study of ketamine as a treatment for OCD, Dr. Rodriguez 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 called hydroxinorketamine (RR-HNK) that could potentially mimic the therapeutic effects of ketamine without side effects like nausea and disassociation. Insights gained from this project could help promote a potentially beneficial medication course for people with OCD who do not respond to available treatments.
Innovator Award Recipients
Assessing correlates of neuroinflammation in children with PANDAS, obsessive compulsive disorder, and healthy controls using Magnetic Resonance Imaging
Primary Investigator: Kyle Williams, MD, PhD
Massachusetts General Hospital (Boston, MA)
Award Amount: $299,018.00
Category: Neuroinflammation; Neuroscience; PANDAS/PANS
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, yet these approaches are limited for use, especially in children. Dr. Williams and his team 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
Primary Investigator: Bethany Wootton, PhD
University of Technology Sydney (Sydney, Australia)
Award Amount: $292,040.00
Cognitive behavioral therapy (CBT), including exposure and response prevention (ERP), is a proven and effective treatment for obsessive-compulsive disorder (OCD). However, many people with OCD are unable to access effective treatment that is both affordable and located near where they live. Recently, Internet-based CBT (ICBT) has helped overcome many barriers to access, but more information is needed to understand which patients would best qualify for it.
In this study, Dr. Wootton and her team 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. The first step in their program of research was to examine what are the most common and consistent predictors of outcome in the literature and what are some novel predictors (i.e., those that haven’t been examined before) that could be examined in their ICBT treatment. By analyzing eight prior studies with a total sample of 359 participants, the resulting publication (McDonald et al., 2023) showed that pre-treatment factors such as severity, past treatments, and avoidance, as well as during-treatment factors such as poor therapist-client alliance and not adhering to treatment, are crucial for recommending the right treatment program. The second step was to demonstrate that people with OCD do not experience spontaneous remission—that is, that their symptoms do not suddenly go away without treatment. This is important because the team is using an open trial methodology in their treatment study, and needs to show that any symptom change that resulted was due to the treatment program rather than people’s symptoms getting better on their own. By analyzing 12 studies with 351 participants, Melkonian et al. (2022) showed that people assigned to control groups do not generally improve in OCD symptoms; only 4% "spontaneously" recover. Finally, Dr. Wootton and her team recruited 323 people to take part in an ICBT treatment for OCD and measured a variety of variables thought to predict outcomes. The team is currently conducting a data analysis from this study.
McDonald, S., Melkonian, M., Karin, E., Dear, B., Titov, N., & Wootton, B. (2023). Predictors of response to cognitive behavioural therapy (CBT) for adults with obsessive-compulsive disorder (OCD): A systematic review. Behavioural and Cognitive Psychotherapy, 1-18. https://doi.org/10.1017/S1352465823000103
*Melkonian, M., McDonald, S., Scott, A., Dear, B.F., Karin, E., & Wootton, B.M. (2022). Symptom improvement and remission in untreated adults seeking treatment for obsessive-compulsive disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 318(1), 175-184. https://doi.org/10.1016/j.jad.2022.08.037
Young Investigator Award Recipients
Circadian Rhythm Changes as a Predictor of OCD Symptom Severity and Outcome in Residential Treatment
Primary Investigator: Jacob Nota, PhD
McLean Hospital/Harvard Medical School (Belmont, MA)
Award Amount: $49,944.00
Category: Sleep and OCD
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.
This study by Dr. Nota and his team aimed to clarify the cause and effect relationship between sleep and OCD symptoms, and what role sleep plays in patients with severe and treatment-resistant OCD. 23 participants with OCD who underwent four weeks of intensive residential treatment had their melatonin production measured to understand whether differences in circadian rhythms and when they go to sleep are related to OCD severity. Over those four weeks, the production of melatonin began to happen earlier on average; the time patients went to sleep, their length of sleep, and their circadian rhythms shifted toward general population averages. The results of this study are in the process of being published.
Celecoxib as an adjunct to treatment as usual in childhood-onset OCD: A double-blind randomized controlled trial
Primary Investigator: Clara Westwell-Roper, MD, PhD
British Columbia Children's Hospital Research Institute (Vancouver, British Columbia, Canada)
Award Amount: $33,038.00
Category: PANDAS/PANS; Pediatric OCD; Pharmacology; Treatment
PANDAS/PANS is associated with neuroinflammation that leads to sudden and acute OCD symptoms developing in children, seemingly overnight. Non-steroidal anti-inflammatory drugs (NSAIDs) like celecoxib (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.
In this study, Dr. Westwell-Roper and her team are conducting 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. By recruiting a target of 80 young participants with OCD (aged 7-18), splitting them into two groups( with all receiving treatment-as-usual, one will receive 100 mg of celecoxib twice a day and one will receive a placebo), and looking at changes to OCD symptoms at six and 12 weeks, the team aims to understand whether celecoxib can help reduce symptoms patients with pediatric OCD. The team published a protocol for a phase II study.
*Westwell-Roper, C., Best, J.T., Elbe, D., MacFadden, M., Baer, S., Tucker, L., Au, A., Naqqash, Z., Lin, B., Lu, C., & Stewart, S.E. (2022). Celecoxib versus placebo as an adjunct to treatment-as-usual in children and youth with obsessive-compulsive disorder: Protocol for a single-site randomised quadruple-blind phase II study. BMJ Open, 12:e054296. doi:10.1136/bmjopen-2021-054296.
Identification of Peripheral Biomarkers of Antidepressant Response in Obsessive Compulsive Disorder
Primary Investigator: Gwyneth Zai, MD, PhD
Centre for Addiction and Mental Health (Toronto, Ontario, Canada)
Award Amount: $50,000.00
Although many options are available, 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 and her team seek to reveal biomarkers that can be identified through a blood test, which could predict the type of antidepressant that will work best for each unique patient. Using a sample of 50 people with OCD who have responded well to antidepressants and 50 who did not respond to two or more antidepressants, the team is investigating the differences in genetic markers, as well as those that correspond to genetic and environmental changes. Through these efforts, it would be possible to match patients with effective medication immediately, which could dramatically improve outcomes for many people with OCD.
Breakthrough Award Recipient
Identifying the molecular and cellular substrates of OCD using human post-mortem brain
Primary Investigator: Susanne Ahmari, MD, PhD
University of Pittsburgh (Pittsburgh, PA)
Award Amount: $500,000.00
Brain imaging studies in OCD patients have consistently shown abnormal activity in regions involved in decision-making (orbitofrontal cortex [OFC]) and transmission of sensory information (thalamus). However, we have no knowledge regarding the changes in these regions happening on a molecular level that contribute to abnormal function in people with OCD.
To fill this gap, Dr. Ahmari’s prior work focused on targeted gene expression studies that showed down-regulation of genes in the OFC associated with excitatory synaptic transmission – essentially leading to less efficient decision-making. However, what is causing these concerted changes? One cohesive explanation is that an OFC input structure, such as the thalamus, acts as the source of molecular changes, and that the OFC compensates accordingly when it receives this input from the thalamus. Dr. Ahmari and her team will investigate this further by using RNA-sequencing in post-mortem OFC and thalamus brain tissue from OCD patients and a matched post-mortem control group. The goal is to uncover the biological networks most affected in OCD patients, through techniques such as differential gene expression, gene co-expression, and pathway analysis. Together, these experiments will lead to identifying key molecular changes underlying the pathology of OCD, with the ultimate goal of finding novel targets and developing more effective treatments.
Young Investigator Award Recipients
Neural mechanisms of avoidance in exposure and response prevention for OCD
Primary Investigator: Martha Falkenstein, PhD
Co-mentors: Courtney Beard, PhD and Christian Webb, PhD
McLean Hospital/Harvard Medical School (Belmont, MA)
Award Amount: $39,766.00
Many patients with OCD who successfully complete 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 and her team 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 50 participants receiving ERP for OCD at McLean Hospital’s OCD Institute, with a subset of these participants receiving “approach-avoidance training” in addition to ERP. In this training, participants will use a smartphone app which simulates “pulling” images associated with their OCD triggers toward them, and “pushing” 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. This study will investigate whether ERP treatment outcomes can be improved and enhanced with the addition of this approach-avoidance training.
A virtual reality study of cognitive biases in body dysmorphic disorder
Primary Investigator: Berta Summers, MA
Massachusetts General Hospital/Harvard Medical School (Boston, MA)
Award Amount: $44,856.00
Category: Body dysmorphic disorder
Previous research has found that people with body dysmorphic disorder (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.
This study by Ms. Summers and her team investigated this phenomenon by presenting simulated social interactions to patients with BDD using virtual reality (VR) technology. 25 participants with BDD and 25 healthy controls took part in a VR module consisting of 13 scenarios made to evoke social ambiguity, in order to compare their interpretations of social situations and see if there are patterns of discomfort in both groups during VR. Compared to control participants, participants with BDD were more likely to have appearance-related threat biases, higher discomfort, and more negative interpretation of ambiguous social scenarios. The study demonstrated that VR is an acceptable and feasible way of providing information about the cognitive biases of people with BDD related to situations that appear threatening in the moment.
Summers, B.J., Schwartzberg, A.C., & Wilhelm, S. (2021). A virtual reality study of cognitive biases in body dysmorphic disorder. Journal of Abnormal Psychology, 130(1), 26-33. https://doi.org/10.1037/abn0000563
Active avoidance of threat cues and fear extinction in obsessive compulsive disorder
Primary Investigator: Michael Wheaton, PhD
Barnard College (New York, NY)
Award Amount: $50,000.00
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
Primary Investigator: Henry Willis, MA
University of North Carolina at Chapel Hill (Chapel Hill, NC)
Award Amount: $25,826.00
Category: Race, Ethnicity, and Diversity
Past research has shown that people with OCD experience worsened symptoms when under stress. Some stressors are unique to distinct identities and statuses in a larger society. For African Americans in the United States, racial discrimination is one of these unique stressors.
Mr. Willis and his team 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 regarding African Americans and OCD, 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 2022 Grant Review Committee:
Christopher Pittenger, MD, PhD - Yale University (Chair)
Jennifer Freeman, PhD - Butler Hospital/Brown University (Vice Chair)
Thomas Adams, PhD - University of Kentucky
Dritan Agalliu, PhD - Columbia University
Susanne Ahmari, MD, PhD - University of Pittsburgh
Rebecca Anderson, PhD - Curtin University
Paul Arnold, MD, PhD - University of Calgary
Catherine Ayers, PhD - University of California San Diego
Novin Balafkan, PhD - Yale University
David Barker, PhD - Brown University
Cynthia Battle, PhD - Brown University
Kristen Benito, PhD - Brown University/Butler Hospital
Michael Bloch, MD - Yale University
Christiana Bratiotis, MSW, PhD - University of British Columbia
Alexander Bystritsky, MD, PhD - University of California, Los Angeles
Matthew Carper, PhD - Brown University
Gregory Chasson, PhD - Illinois Institute of Technology
Terence Ching, PhD - Yale University
Christine Conelea, PhD - University of Minnesota
Madeleine Cunningham, PhD - University of Oklahoma
Michael Daines, MD - University of Arizona
Justine Dembo, MD, FRCPC - University of Toronto
Darin Dougherty, MD - Massachusetts General Hospital/Harvard Medical School
Stephanie Dulawa, PhD - University of California, San Diego
Lara Farrell, PhD - Griffith University
Thomas Fernandez, MD - Yale University
Jamie Feusner, MD - University of California Los Angeles
Martijn Figee, MD, PhD - Icahn School of Medicine at Mount Sinai
Leonardo Fontenelle, MD, PhD - Universidade Federal do Rio de Janeiro
Martin Franklin, PhD - Rogers Behavioral Health
Jennifer Frankovich, MD - Stanford University
Jennifer Freeman, PhD - Butler Hospital/Brown University
Sarah Garnaat, PhD - Brown University
Wayne Goodman, MD - Baylor College of Medicine
Jon Grant, JD, MD, MPH - University of Chicago
Jennifer Greenberg, PsyD - Massachusetts General Hospital/Harvard Medical School
Jessica Grisham, PhD - University of New South Wales, Sydney
Edna Grünblatt, PhD - University of Zurich
Robert Hudak, MD - University of Pittsburgh
Ryan Jacoby, PhD - Harvard University/Massachusetts General Hospital
Reilly Kayser, MD - Columbia University
Benjamin Kelmendi, MD - Yale University
Joshua Kemp, PhD - Brown University/Butler Hospital
James Knowles, MD, PhD - State University of New York, Downstate
Lorrin Koran, MD - Stanford University
Gayle Maloney, PhD - Yale University
David Mataix-Cols, PhD - Karolinska Institutet
Nicole McLaughlin, PhD - Brown University
Jeffrey Miller, MD - Columbia University
Steffen Moritz, PhD - University Medical Center, Hamburg
Andrew Moses Lee, MD, PhD - University of California, San Francisco
Naveen Nagarajan, PhD - University of Utah
Melissa Norberg, PhD - Macquarie University
Jacob Nota, PhD - McLean Hospital/Harvard Medical School
David Nutt, DM, FRCP - Imperial College London
Erin O’Connor, PhD - Brown University
Bunmi Olatunji, PhD - Vanderbilt University
Edward Pace-Schott, PhD - Harvard Medical School
Michele Pato, MD - Rutgers University
Tara Peris, PhD - University of California, Los Angeles
Katharine Phillips, MD - Weill Cornell Medical College
Anthony Pinto, PhD - Zucker Hillside Hospital/Northwell Health
Christopher Pittenger, MD, PhD - Yale University
Renato Polimanti, PhD - Yale School of Medicine
Andrea Pozza, PhD - University of Siena
Peggy Richter, MD, FRCP - University of Toronto
Bradley Riemann, PhD - Rogers Behavioral Health
Carolyn Rodriguez, MD, PhD - Stanford University
Sanjaya Saxena, MD - University of California, San Diego
H. Blair Simpson, MD, PhD - Columbia University
Gail Steketee, PhD - Boston University
Emily Stern, PhD - New York University/Research Foundation for Mental Hygiene
Eric Storch, PhD - Baylor College of Medicine
Margo Thienemann, MD - Stanford University
Kiara Timpano, PhD - University of Miami
Peter Tuerk, PhD - University of Virginia
Michael Twohig, PhD - Utah State University
Daniel Tylee, MD, PhD - Yale School of Medicine
Anna Van Meter, PhD - New York University
Barbara Van Noppen, PhD - University of Southern California
Hilary Weingarden, PhD - Massachusetts General Hospital/Harvard University
Chad Wetterneck, PhD - University of Wisconsin, Milwaukee
Michael Wheaton, PhD - Barnard College
Kyle Williams, MD, PhD - Harvard University
Monnica Williams, PhD - University of Ottawa
Bethany Wootton, PhD - University of Technology, Sydney
Brian Zaboski, PhD - Yale University