Research Grant Recipients

Breakthrough Awards

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

Category: Treatment

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

Category: Neuroscience

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

Category: Pharmacology

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

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

Category: Genetics

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

Category: Treatment

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.

Resulting Publication:

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

Category: Treatment

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
Stockholm, Sweden
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
Postdoctoral Fellow
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
Assistant Professor-in-Residence
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
Postdoctoral Associate
Yale University
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
Resident, PGY-4
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
Post-Doctoral Research
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

Wei Li
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.

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