Dr. Carolyn Rodriguez utilizes her training as a psychiatrist, neuroscientist, and clinical researcher to innovate rapid-acting treatments to relieve the suffering of patients with severe mental illnesses, including Obsessive-Compulsive Disorder (OCD). She has led landmark clinical trials that pioneered new targeted treatments and investigated the role of glutamatergic and opioid pathways. As the Director of the Translational Therapeutics Lab and Assistant Professor in the Department of Psychiatry and Behavioral Science, she developed methods that combine in vivo drug infusions with magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI) and electroencephalograpy (EEG) to map human brain circuit dysfunction in real time. This experimental medicine approach is critical to understanding the brain basis of psychiatric illnesses and will transform mental health care.
Carolyn is currently engaged in NIH, foundation, and donor funded mechanistic and clinical efficacy studies of glutamate-modulating compounds, non-invasive brain stimulation, and psychotherapy in OCD. Additional studies focus on understanding the brain mechanisms involved in hoarding disorder and how hording behaviors differ from normal collecting. Carolyn also provides mental health care for Veterans as a Consultation-Liaison psychiatrist at the Palo Alto Veterans Affairs.
Carolyn serves as Associate Chair for Inclusion and Diversity in the Department of Psychiatry, Vice Chair for the Research Council of the American Psychiatric Association, Vice Chair for the International OCD Foundation Research Symposium, and Director, Executive Board of International College of Obsessive Compulsive Spectrum Disorders. She has won several national awards, including most recently, the 2017 Eva King-Killam Award for Outstanding Translational Research. Her research has been highlighted by organizations including NPR, PBS, New York Times, ABC News, NBC News, Newsweek, and Time.com. To educate the public on research findings and resources for clinical care, Carolyn contributes articles for Huffington Post and Harvard Business Review.
Carolyn received her B.S. in Computer Science from Harvard University in 1996, followed by a Ph.D. in Neuroscience and Genetics from Harvard Medical School and an M.D. from Harvard Medical School-M.I.T. in 2004. Born in San Juan, Puerto Rico, she now lives with her husband and 3 children in Palo Alto.
Associate Professor, Psychiatry and Behavioral Sciences
Member, Wu Tsai Neurosciences Institute
Associate Chair - Inclusion and Diversity, Stanford Medical School, Department of Psychiatry and Behavioral Sciences (2018 - Present)
Director, Translational Therapeutics/Rodriguez Lab (2015 - Present)
Director, Translational OCD Research Program (2015 - Present)
Director, Stanford Hoarding Disorders Research Program (2015 - Present)
Clinical Lab Director, Stanford Center for Cognitive and Neurobiological Imaging (CNI) (2018 - Present)
Honors & Awards
Chairman’s Annual Award for Excellence Across Multiple Missions, Stanford Medical School, Department of Psychiatry and Behavioral Sciences (2018)
Eva King Killam Research Award for Outstanding Translational Research Contributions, American College of Neuropsychopharmacology (2017)
A.E. Bennett Research Award for Outstanding Contributions to Clinical/Translational Research, Society for Biological Psychiatry (SOBP) (2017)
Gerald R. Klerman Award Honorable Mention for outstanding clinical research achievement, Brain and Behavior Research Foundation (BBRF/NARSAD) (2017)
Harold Amos Medical Faculty Development Award, Robert Wood Johnson Foundation (2015)
Neuropsychopharmacology Editor's Award for Tranformative Original Report (NEATOR) Award, American College of Neuropsychopharmacology (2014)
Robins/Guze Award, American Psychopathological Association (2014)
Boards, Advisory Committees, Professional Organizations
Vice Chairperson, Council on Research, American Psychiatric Association (APA) (2016 - Present)
Director, Executive Board of the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) (2015 - Present)
Co-Chair, International OCD Foundation (IOCDF) Research Symposium (2018 - Present)
Editorial Board Member, Neuropsychopharmacology Journal (2018 - Present)
Scientific And Clinical Advisory Board Member, International OCD Foundation (IOCDF) (2018 - Present)
Scientific Program Committee, American Psychiatric Association (APA) (2016 - Present)
Scientific Advisory Board Member, OCD Research Partnership (2018 - Present)
Advisory Board Member, Stanford Center for Cognitive and Neurobiological Imaging (CNI) (2018 - Present)
Chair, American College of Neuropsychopharmacology (ACNP) Minority Task Force (2017 - 2018)
Co-Chair, American College of Neuropsychopharmacology (ACNP) Minority Task Force (2016 - 2017)
Chair, OCD Practice Guidelines Work Group, Anxiety and Depression Association of America (ADAA) (2015 - 2016)
Secretary General, American Society of Hispanic Psychiatry (2012 - 2014)
Laughlin Fellow, American College of Psychiatrists (2007 - 2009)
PhD Training:Harvard Medical School (2004) MA
Fellowship:Columbia University (2011) NY
Board Certification: Psychiatry, American Board of Psychiatry and Neurology (2009)
Residency:Columbia Presbyterian Medical Center (2008) NY
BS, Harvard University, Computer Science (1996)
Internship:Columbia Presbyterian Medical Center (2005) NY
PhD, Harvard Medical School, Neuroscience (2004)
MD, Harvard Medical School and Massachusetts Institute of Technology, Health Sciences and Technology (2004)
Medical Education:Harvard Medical School (2004) MA
Residency, Columbia University-NYSPI, Psychiatry (2008)
Board Certification, Psychiatry, American Board of Psychiatry and Neurology (2009)
Enhancing Treatment of Hoarding Disorder With Personalized In-Home Sorting and Decluttering Practice
The proposed study aims to investigate the efficacy of adding in-home decluttering practice to Buried in Treasures Workshop (BIT) facilitated group treatment for hoarding disorder.
Exploring Nitrous Oxide Effects for Post Traumatic Stress Disorder (PTSD)
The purpose of this study is to understand nitrous oxide effects in post traumatic stress disorder (PTSD)
Neural Mechanisms of Decision Making in Hoarding Disorder
The purpose of this study is to understand the neural mechanisms of decision making in hoarding disorder.
Rapid Non-Invasive Brain Stimulation for OCD (oTMS)
The purpose of this study is to understand how cortical stimulation affects Obsessive-Compulsive Disorder (OCD) symptoms.
Understanding How Ketamine Brings About Rapid Improvement in OCD
The purpose of this study is to understand how ketamine brings about rapid improvement in Obsessive-Compulsive Disorder (OCD) symptoms.
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
The American journal of psychiatry
OBJECTIVE: In addition to N-methyl-d-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of this study was to determine whether opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant or dissociative effects.METHOD: In a proposed double-blind crossover study of 30 adults with treatment-resistant depression, the authors performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: placebo or 50 mg of naltrexone preceding intravenous infusion of 0.5 mg/kg of ketamine. Response was defined as a reduction ≥50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D) score on postinfusion day 1.RESULTS: In the interim analysis, seven of 12 adults with treatment-resistant depression met the response criterion during the ketamine plus placebo condition. Reductions in 6-item and 17-item HAM-D scores among participants in the ketamine plus naltrexone condition were significantly lower than those of participants in the ketamine plus placebo condition on postinfusion days 1 and 3. Secondary analysis of all participants who completed the placebo and naltrexone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis.CONCLUSIONS: The findings suggest that ketamine's acute antidepressant effect requires opioid system activation. The dissociative effects of ketamine are not mediated by the opioid system, and they do not appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.
View details for DOI 10.1176/appi.ajp.2018.18020138
View details for PubMedID 30153752
- Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of Concept. The American journal of psychiatry 2016; 173 (12): 1239–41
In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept
2015; 233 (2): 141-147
We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy ((1)H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology.
View details for DOI 10.1016/j.pscychresns.2015.06.001
View details for Web of Science ID 000359313300010
View details for PubMedID 26104826
Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
2013; 38 (12): 2475-2483
Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
View details for DOI 10.1038/npp.2013.150
View details for Web of Science ID 000325710200016
View details for PubMedID 23783065
- Interpreting Ketamine's Opioid Receptor Dependent Effect: Response to Sanacora. The American journal of psychiatry 2019; 176 (3): 249–50
- Target Population, Dose, and Timing Considerations for Understanding Naltrexone's Subjective Effect: Response to Amiaz. The American journal of psychiatry 2019; 176 (3): 251–52
- Exploring Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Extinction Learning-Based Treatment Outcome in Obsessive-Compulsive Disorder: A Pilot Study. Journal of clinical psychopharmacology 2018
Augmenting Buried in Treasures with in-home uncluttering practice: Pilot study in hoarding disorder.
Journal of psychiatric research
2018; 107: 145–50
Hoarding disorder is characterized by difficulty parting with possessions and by clutter that impairs the functionality of living spaces. Cognitive behavioral therapy conducted by a therapist (individual or in a group) for hoarding symptoms has shown promise. For those who cannot afford or access the services of a therapist, one alternative is an evidence-based, highly structured, short-term, skills-based group using CBT principles but led by non-professional facilitators (the Buried in Treasures [BIT] Workshop). BIT has achieved improvement rates similar to those of psychologist-led CBT. Regardless of modality, however, clinically relevant symptoms remain after treatment, and new approaches to augment existing treatments are needed. Based on two recent studies - one reporting that personalized care and accountability made treatments more acceptable to individuals with hoarding disorder and another reporting that greater number of home sessions were associated with better clinical outcomes, we tested the feasibility and effectiveness of adding personalized, in-home uncluttering sessions to the final weeks of BIT. Participants (n = 5) had 15 sessions of BIT and up to 20 hours of in-home uncluttering. Reductions in hoarding symptoms, clutter, and impairment of daily activities were observed. Treatment response rate was comparable to rates in other BIT studies, with continued improvement in clutter level after in-home uncluttering sessions. This small study suggests that adding in-home uncluttering sessions to BIT is feasible and effective.
View details for DOI 10.1016/j.jpsychires.2018.10.001
View details for PubMedID 30419524
Electroencephalographic Biomarkers for Treatment Response Prediction in Major Depressive Illness: A Meta-Analysis.
The American journal of psychiatry
OBJECTIVE:: Reducing unsuccessful treatment trials could improve depression treatment. Quantitative EEG (QEEG) may predict treatment response and is being commercially marketed for this purpose. The authors sought to quantify the reliability of QEEG for response prediction in depressive illness and to identify methodological limitations of the available evidence.METHOD:: The authors conducted a meta-analysis of diagnostic accuracy for QEEG in depressive illness, based on articles published between January 2000 and November 2017. The review included all articles that used QEEG to predict response during a major depressive episode, regardless of patient population, treatment, or QEEG marker. The primary meta-analytic outcome was the accuracy for predicting response to depression treatment, expressed as sensitivity, specificity, and the logarithm of the diagnostic odds ratio. Raters also judged each article on indicators of good research practice.RESULTS:: In 76 articles reporting 81 biomarkers, the meta-analytic estimates showed a sensitivity of 0.72 (95% CI=0.67-0.76) and a specificity of 0.68 (95% CI=0.63-0.73). The logarithm of the diagnostic odds ratio was 1.89 (95% CI=1.56-2.21), and the area under the receiver operator curve was 0.76 (95% CI=0.71-0.80). No specific QEEG biomarker or specific treatment showed greater predictive power than the all-studies estimate in a meta-regression. Funnel plot analysis suggested substantial publication bias. Most studies did not use ideal practices.CONCLUSIONS:: QEEG does not appear to be clinically reliable for predicting depression treatment response, as the literature is limited by underreporting of negative results, a lack of out-of-sample validation, and insufficient direct replication of previous findings. Until these limitations are remedied, QEEG is not recommended for guiding selection of psychiatric treatment.
View details for DOI 10.1176/appi.ajp.2018.17121358
View details for PubMedID 30278789
- Deepening the Understanding of the Psychomotor Response to Critical Illness CRITICAL CARE MEDICINE 2018; 46 (7): E722
- EXPLORING SOCIODEMOGRAPHIC AND CLINICAL CORRELATES OF OLDER ADULTS WITH OBSESSIVE-COMPULSIVE DISORDER: A REPORT FROM THE INTERNATIONAL COLLEGE OF OBSESSIVE-COMPULSIVE DISORDERS (ICOCS) ELSEVIER SCIENCE BV. 2018: 765–66
Clinical Implementation of Pharmacogenetic Decision Support Tools for Antidepressant Drug Prescribing.
The American journal of psychiatry
The accrual and analysis of genomic sequencing data have identified specific genetic variants that are associated with major depressive disorder. Moreover, substantial investigations have been devoted to identifying gene-drug interactions that affect the response to antidepressant medications by modulating their pharmacokinetic or pharmacodynamic properties. Despite these advances, individual responses to antidepressants, as well as the unpredictability of adverse side effects, leave clinicians with an imprecise prescribing strategy that often relies on trial and error. These limitations have spawned several combinatorial pharmacogenetic testing products that are marketed to physicians. Typically, combinatorial pharmacogenetic decision support tools use algorithms to integrate multiple genetic variants and assemble the results into an easily interpretable report to guide prescribing of antidepressants and other psychotropic medications. The authors review the evidence base for several combinatorial pharmacogenetic decision support tools whose potential utility has been evaluated in clinical settings. They find that, at present, there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects.
View details for DOI 10.1176/appi.ajp.2018.17111282
View details for PubMedID 29690793
DISTURBANCES IN NEURAL OSCILLATIONS, GLUTAMATE, AND GABA: EFFECTS OF KETAMINE AND COMPARISON TO SCHIZOPHRENIA
OXFORD UNIV PRESS. 2018: S2
View details for Web of Science ID 000429541800007
- Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder. The Journal of clinical psychiatry 2018; 79 (1)
Challenges Testing Intranasal Ketamine in Obsessive-Compulsive Disorder (OCD)
NATURE PUBLISHING GROUP. 2017: S128–S129
View details for Web of Science ID 000416846301028
- Embracing Uncertainty as a First-Year Therapist Treating a Patient Who Has Obsessive-Compulsive Disorder. Psychiatric services 2017; 68 (5): 433-434
Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).
Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients.A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson's chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable.14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables.Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.
View details for DOI 10.1017/S1092852917000177
View details for PubMedID 28300008
Acceptability of treatments and services for individuals with hoarding behaviors
JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS
2016; 11: 1-8
To explore the acceptability of currently available treatments and services for individuals who self-report hoarding behaviors.Between 10/2013 and 8/2014, participants were invited to complete an online survey that provided them descriptions of eleven treatments and services for hoarding behaviors and asked them to evaluate their acceptability using quantitative (0 [not at all acceptable] -10 [completely acceptable]) Likert scale ratings. The a priori definition of acceptability for a given resource was an average Likert scale score of six or greater. Two well-validated self-report measures assessed hoarding symptom severity: the Saving Inventory-Revised and the Clutter Image Rating Scale.Two hundred and seventy two participants who self-reported having hoarding behaviors completed the questionnaire. Analyses focused on the 73% of responders (n=203) who reported clinically significant hoarding behaviors (i.e., Saving Inventory-Revised scores of ≥40). The three most acceptable treatments were individual cognitive behavioral therapy (6.2 ±3.1 on the Likert scale), professional organizing service (6.1 ±3.2), and use of a self-help book (6.0 ±3.0).In this sample of individuals with self-reported clinically significant hoarding behaviors (n=203), only 3 out of 11 treatments and services for hoarding were deemed acceptable using an a priori score. While needing replication, these findings indicate the need to design more acceptable treatments and services to engage clients and maximize treatment outcomes for hoarding disorder.
View details for DOI 10.1016/j.jocrd.2016.07.001
View details for Web of Science ID 000391774100001
View details for PubMedID 28163996
View details for PubMedCentralID PMC5287410
- Open-Label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. journal of clinical psychiatry 2016; 77 (5): 688-689
An investigation of the role of intolerance of uncertainty in hoarding symptoms.
Journal of affective disorders
2016; 193: 208-214
Hoarding disorder (HD) is a common, debilitating mental illness and public health burden. Understanding the factors that contribute to hoarding is critical for identifying treatment targets. As a relatively new diagnostic entity, this research remains in its initial stages. Intolerance of uncertainty (IU) is thought to be a vulnerability factor for generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD), and may also be relevant to HD. We investigated the possible association between IU and hoarding in two sets of analyses.First, we administered self-report measures of IU and hoarding symptoms to unscreened undergraduate students (N=456) and used regressions to probe their association controlling for relevant covariates. Second, in a clinical sample, we compared IU across groups of patients with HD (N=26), GAD (N=26), OCD (N=51), other anxiety disorders (N=91) and healthy controls (N=29).In the student sample, IU predicted hoarding symptoms above and beyond relevant covariates, including hoarding-related beliefs. In the clinical sample, HD patients evidenced greater IU relative to healthy individuals and the mixed anxiety group, and comparable levels of IU to the GAD and OCD groups.This study relied exclusively on self-report questionnaires and a cross-sectional design.IU is associated with hoarding behavior and, as we discuss, conceptual models might benefit from the study of IU as a potentially contributing factor. Directions for future research are discussed.
View details for DOI 10.1016/j.jad.2015.12.047
View details for PubMedID 26773912
- Can exposure-based CBT extend the effects of intravenous ketamine in obsessive-compulsive disorder? an open-label trial. journal of clinical psychiatry 2016; 77 (3): 408-409
A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder.
2016; 21 (3): 320–27
The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.
View details for DOI 10.1038/mp.2015.83
View details for PubMedID 26283639
Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder.
Human brain mapping
Deficits in attention have been implicated in Obsessive-Compulsive Disorder (OCD), yet their neurobiological bases are poorly understood. In unmedicated adults with OCD (n = 30) and healthy controls (n = 32), they used resting state functional connectivity MRI (rs-fcMRI) to examine functional connectivity between two neural networks associated with attentional processes: the default mode network (DMN) and the salience network (SN). They then used path analyses to examine putative relationships across three variables of interest: DMN-SN connectivity, attention, and OCD symptoms. In the OCD compared with healthy control participants, there was significantly reduced inverse connectivity between the anterior medial prefrontal cortex (amPFC) and the anterior insular cortex, regions within the DMN and SN, respectively. In OCD, reduced inverse DMN-SN connectivity was associated with both increased OCD symptom severity and decreased sustained attention. Path analyses were consistent with a potential mechanistic explanation: OCD symptoms are associated with an imbalance in DMN-SN networks that subserve attentional processes and this effect of OCD on DMN-SN connectivity is associated with decreased sustained attention. This work builds upon a growing literature suggesting that reduced inverse DMN-SN connectivity may represent a trans-diagnostic marker of attentional processes and suggests a potential mechanistic account of the relationship between OCD and attention. Reduced inverse DMN-SN connectivity may be an important target for treatment development to improve attention in individuals with OCD. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.23408
View details for PubMedID 27659299
- Bridging the Divide: Advances and Challenges in Understanding the Impact of Race and Ethnicity on the Mental Health of Older Adults AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY 2015; 23 (6): 545-547
Six-Month Outcomes From a Randomized Trial Augmenting Serotonin Reuptake Inhibitors With Exposure and Response Prevention or Risperidone in Adults With Obsessive-Compulsive Disorder
JOURNAL OF CLINICAL PSYCHIATRY
2015; 76 (4): 440-446
To compare outcomes after 6-month maintenance treatment of adults diagnosed with obsessive-compulsive disorder (OCD) based on DSM-IV criteria who responded to acute treatment with serotonin reuptake inhibitors (SRIs) augmented by exposure and response prevention (EX/RP) or risperidone.A randomized trial was conducted at 2 academic sites from January 2007 through December 2012. In the acute phase, 100 patients on therapeutic SRI dose with at least moderate OCD severity were randomized to 8 weeks of EX/RP, risperidone, or pill placebo. Responders entered the 6-month maintenance phase, continuing the augmentation strategy they received acutely (n = 30 EX/RP, n = 8 risperidone). Independent evaluations were conducted every month. The main outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).Intent-to-treat analyses indicated that, after 6-month maintenance treatment, EX/RP yielded OCD outcomes that were superior to risperidone (Y-BOCS = 10.95 vs 18.70; t40 = 2.76, P = .009); more patients randomized to EX/RP met response criteria (Y-BOCS decrease ≥ 25%: 70% vs 20%; P < .001) and achieved minimal symptoms (Y-BOCS ≤ 12: 50% vs 5%; P < .001). During maintenance, OCD severity decreased slightly in both conditions (Y-BOCS decrease = 2.2 points, P = .020). Lower Y-BOCS at entry to maintenance was associated with more improvement in both conditions (r38 = 0.57, P < .001).OCD patients taking SRIs who responded to acute EX/RP or risperidone maintained their gains over 6-month maintenance. Because EX/RP patients improved more during acute treatment than risperidone-treated patients, and both maintained their gains during maintenance, EX/RP yielded superior outcomes 6 months later. The findings that 50% of patients randomized to EX/RP had minimal symptoms at 6-month maintenance, a rate double that of prior studies, suggests that EX/RP maintenance helps maximize long-term outcome.ClinicalTrials.gov identifier: NCT00389493.
View details for DOI 10.4088/JCP.14m09044
View details for Web of Science ID 000354997500025
View details for PubMedID 25375780
- Canned art. The Lancet. Psychiatry 2015; 2 (8): 690–91
Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder A Randomized Clinical Trial
2013; 70 (11): 1190-1198
Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.clinicaltrials.gov Identifier: NCT00389493.
View details for DOI 10.1001/jamapsychiatry.2013.1932
View details for Web of Science ID 000328948700011
View details for PubMedID 24026523
Prevalence and Correlates of Difficulty Discarding Results From a National Sample of the US Population
JOURNAL OF NERVOUS AND MENTAL DISEASE
2013; 201 (9): 795-801
This study presents nationally representative data on the prevalence and the correlates of difficulty discarding, a behavior described in many psychiatric disorders, including a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, called hoarding disorder. Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions, a national sample of the US population (N=43,093). Difficulty discarding worn-out/worthless items (assessed by a single item) and diagnoses of psychiatric disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The prevalence of difficulty discarding worn-out/worthless items in the general population was 20.6%. Difficulty discarding strongly correlated with axis I and axis II disorders, level of impairment, and use of mental health services. Difficulty discarding worn-out/worthless items is a common behavior that can be associated with various forms of psychopathology. When reported in a clinical setting, it may signal that careful assessment is needed to clarify diagnosis and inform treatment strategies.
View details for DOI 10.1097/NMD.0b013e3182a21471
View details for Web of Science ID 000330375300011
View details for PubMedID 23995036
- Does Extended Release Methylphenidate Help Adults With Hoarding Disorder? A Case Series JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY 2013; 33 (3): 444-447
Public-Academic Partnerships A Rapid Small-Grant Program for Policy-Relevant Research: Motivating Public-Academic Partnerships
2013; 64 (2): 106-108
To help grow a cadre of researchers with the knowledge and skills to pursue topics of great utility to public mental health systems, the director of the Division of Mental Health Services and Policy Research at Columbia University used funding from the New York State Office of Mental Health (OMH) to create a rapid small-grant program called the OMH Policy Scholars Program. This column uses two case examples to describe how this public-academic partnership exposes early-career researchers to the needs and complexities of large public mental health systems while providing them with senior research and policy mentors to help ensure the success of the scholars' projects and oversee their introduction to and work within the public mental health system. This type of collaboration is one model of encouraging early-career psychiatric researchers to pursue policy-relevant research.
View details for DOI 10.1176/appi.ps.201200519
View details for Web of Science ID 000327260400007
View details for PubMedID 23370621
Prevalence of Hoarding Disorder in Individuals at Potential Risk of Eviction in New York City A Pilot Study
JOURNAL OF NERVOUS AND MENTAL DISEASE
2012; 200 (1): 91-94
This study estimated the prevalence of hoarding disorder (HD) in individuals seeking help from Eviction Intervention Services Housing Research Center (EIS), a not-for-profit community organization in New York City (NYC) that aids clients with housing problems including eviction. One hundred fifteen EIS clients were screened for HD. The prevalence of HD among those seeking help from EIS was 22% (clinician-rated) and 23% (self-rated), which is nearly 5 to 10 times greater than the rate of hoarding (2% to 5%) in the general population. Of individuals seeking help from EIS who met the criteria for HD (n = 25), 32% were currently in legal eviction proceedings (i.e., threatened with imminent eviction), 44% had a history of previous legal eviction proceedings, and 20% had been evicted from their home one or more times, yet only 48% were currently seeking mental health treatment. Almost a quarter of individuals seeking help for housing problems from a community eviction prevention organization met the criteria for HD; only about half of these individuals were receiving mental health treatment. Future studies are needed to determine whether HD treatment can reduce the risk of eviction and homelessness in NYC.
View details for DOI 10.1097/NMD.0b013e31823f678b
View details for Web of Science ID 000298636600013
View details for PubMedID 22210369
- From Clutter to Modern Art: A Chinese Artist's Perspective on Hoarding Behaviors AMERICAN JOURNAL OF PSYCHIATRY 2011; 168 (12): 1248-1248
- Rapid Resolution of Obsessions After an Infusion of Intravenous Ketamine in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY 2011; 72 (4): 567-569
- Minocycline Augmentation of Pharmacotherapy in Obsessive-Compulsive Disorder: An Open-Label Trial JOURNAL OF CLINICAL PSYCHIATRY 2010; 71 (9): 1247-1249
- Diagnosis and Treatment of a Patient With Both Psychotic and Obsessive-Compulsive Symptoms AMERICAN JOURNAL OF PSYCHIATRY 2010; 167 (7): 754-761
- Personalized Intervention for Hoarders at Risk of Eviction PSYCHIATRIC SERVICES 2010; 61 (2): 205-205
- The Role of Culture in Psychodynamic Psychotherapy: Parallel Process Resulting From Cultural Similarities Between Patient and Therapist AMERICAN JOURNAL OF PSYCHIATRY 2008; 165 (11): 1402-1406
Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6
2005; 48 (6): 933-947
The lower rhombic lip (LRL) is a germinal zone in the dorsal hindbrain productive of tangentially migrating neurons, streaming extramurally (mossy fiber neurons) or intramurally (climbing fiber neurons). Here we show that LRL territory, operationally defined by Wnt1 expression, is parceled into molecular subdomains predictive of cell fate. Progressing dorsoventrally, Lmx1a and Gdf7 expression identifies the primordium for hindbrain choroid plexus epithelial cells; Math1, for mossy fiber neurons; and immediately ventral to Math1 yet within Wnt1(+) territory, a climbing fiber primordium dominated by Ngn1-expressing cells. Elimination of Pax6 results in expansion of this Ngn1(+) progenitor pool and reduction in the Math1(+) pool, with accompanying later enlargement of the climbing fiber nucleus and reductions in mossy fiber nuclei. Pax6 loss also disrupts Msx expression cell-nonautonomously, suggesting Pax6 may influence LRL progenitor identity indirectly through potentiating BMP signaling. These studies suggest that underlying the diversity and proportions of fates produced by the LRL is a precise suborganization regulated by Pax6.
View details for DOI 10.1016/j.neuron.2005.11.031
View details for Web of Science ID 000234301700010
View details for PubMedID 16364898
Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation
2003; 35 (1): 70-75
The hindbrain roof plate and choroid plexus are essential organizing centers for inducing dorsal neuron fates and sustaining neuron function. To map the formation of these structures, we developed a broadly applicable, high resolution, recombinase-based method for mapping the fate of cells originating from coordinates defined by intersecting combinations of expressed genes. Using this method, we show that distinct regions of hindbrain roof plate originate from discrete subdomains of rhombencephalic neuroectoderm expressing Wnt1; that choroid plexus, a secretory epithelium important for patterning later-formed hindbrain structures and maintaining neuron function, derives from the same embryonic primordium as the hindbrain roof plate; and that, unlike the floor plate, these dorsal organizing centers develop in a patterned, segmental manner, built from lineage-restricted compartments. Our data suggest that the roof plate and choroid plexus may be formed of functional units that are capable of differentially organizing the generation of distinct neuronal cell types at different axial levels.
View details for DOI 10.1038/ng1228
View details for Web of Science ID 000185018500013
View details for PubMedID 12923530
Switching on lineage tracers using site-specific recombination.
Methods in molecular biology (Clifton, N.J.)
2002; 185: 309-334
View details for PubMedID 11768998
Origin of the precerebellar system
2000; 27 (3): 475-486
The precerebellar system provides the principal input to the cerebellum and is essential for coordinated motor activity. Using a FLP recombinase-based fate mapping approach, we provide direct evidence in the mouse that this ventral brainstem system derives from dorsally located rhombic neuroepithelium. Moreover, by fate mapping at the resolution of a gene expression pattern, we have uncovered an unexpected subdivision within the precerebellar primordium: embryonic expression of Wnt1 appears to identify the class of precerebellar progenitors that will later project mossy fibers from the brainstem to the cerebellum, as opposed to the class of precerebellar neurons that project climbing fibers. Differential gene expression therefore appears to demarcate two populations within the precerebellar primordium, grouping progenitors by their future type of axonal projection and synaptic partner rather than by final topographical position.
View details for Web of Science ID 000089601300012
View details for PubMedID 11055431
- High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP NATURE GENETICS 2000; 25 (2): 139-140
Short-wave cone signal in the red-green detection mechanism
1998; 38 (6): 813-826
Previous work shows that the red-green (RG) detection mechanism is highly sensitive, responding to equal and opposite long-wave (L) and middle-wave (M) cone contrast signals. This mechanism mediates red-green hue judgements under many conditions. We show that the RG detection mechanism also receives a weak input from the short-wave (S) cones that supports the L signal and equally opposes M. This was demonstrated with a pedestal paradigm, in which weak S cone flicker facilitates discrimination and detection of red-green flicker. Also, a near-threshold +S cone flash facilitates detection of red flashes and inhibits green flashes, and a near-threshold -S cone flash facilitates detection of green flashes and inhibits red flashes. The S contrast weight in RG is small relative to the L and M contrast weights. However, a comparison of our results with other studies suggests that the strength of the absolute S cone contrast contribution to the RG detection mechanism is 1/4 to 1/3 the strength of the S contribution to the blue-yellow (BY) detection mechanism. Thus, the S weight in RG is a significant fraction of the S weight in BY. This has important implications for the 'cardinal' color mechanisms, for it predicts that for detection or discrimination, the mechanisms limiting performance do not lie on orthogonal M-L and S axes within the equiluminant color plane.
View details for Web of Science ID 000072768100005
View details for PubMedID 9624432