Carolyn Rodriguez

All Publications

• Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. The American journal of psychiatry Williams, N. R., Heifets, B. D., Blasey, C., Sudheimer, K., Pannu, J., Pankow, H., Hawkins, J., Birnbaum, J., Lyons, D. M., Rodriguez, C. I., Schatzberg, A. F. 2018: appiajp201818020138

  Abstract

  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 Rodriguez, C. I., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H. B., Burch, R. M., Moskal, J. R. 2016; 173 (12): 1239–41

  View details for DOI 10.1176/appi.ajp.2016.16080868

  View details for PubMedID 27903098

• In vivo effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder: Proof of concept PSYCHIATRY RESEARCH-NEUROIMAGING Rodriguez, C. I., Kegeles, L. S., Levinson, A., Ogden, R. T., Mao, X., Milak, M. S., Vermes, D., Xie, S., Hunter, L., Flood, P., Moore, H., Shungu, D. C., Simpson, H. B. 2015; 233 (2): 141-147

  Abstract

  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 NEUROPSYCHOPHARMACOLOGY Rodriguez, C. I., Kegeles, L. S., Levinson, A., Feng, T., Marcus, S. M., Vermes, D., Flood, P., Simpson, H. B. 2013; 38 (12): 2475-2483

  Abstract

  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 Heifets, B. D., Williams, N. R., Blasey, C., Sudheimer, K., Rodriguez, C. I., Schatzberg, A. F. 2019; 176 (3): 249–50

  View details for DOI 10.1176/appi.ajp.2018.18091061r

  View details for PubMedID 30818991

• Target Population, Dose, and Timing Considerations for Understanding Naltrexone's Subjective Effect: Response to Amiaz. The American journal of psychiatry Heifets, B. D., Williams, N. R., Blasey, C., Sudheimer, K., Rodriguez, C. I., Schatzberg, A. F. 2019; 176 (3): 251–52

  View details for DOI 10.1176/appi.ajp.2018.18111231r

  View details for PubMedID 30818989

• Exploring Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Extinction Learning-Based Treatment Outcome in Obsessive-Compulsive Disorder: A Pilot Study. Journal of clinical psychopharmacology Linkovski, O., Wheaton, M. G., Zwerling, J., Odgerel, Z., van Roessel, P., Filippou-Frye, M., Lombardi, A., Wright, B., Steinman, S. A., Simpson, H. B., Lee, F., Rodriguez, C. I. 2018

  View details for DOI 10.1097/JCP.0000000000000994

  View details for PubMedID 30531475

• Augmenting Buried in Treasures with in-home uncluttering practice: Pilot study in hoarding disorder. Journal of psychiatric research Linkovski, O., Zwerling, J., Cordell, E., Sonnenfeld, D., Willis, H., La Lima, C. N., Baker, C., Ghazzaoui, R., Girson, R., Sanchez, C., Wright, B., Alford, M., Varias, A., Filippou-Frye, M., Shen, H., Jo, B., Shuer, L., Frost, R. O., Rodriguez, C. I. 2018; 107: 145–50

  Abstract

  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 Widge, A. S., Bilge, M. T., Montana, R., Chang, W., Rodriguez, C. I., Deckersbach, T., Carpenter, L. L., Kalin, N. H., Nemeroff, C. B. 2018: appiajp201817121358

  Abstract

  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 Kleinman, R. A., Ravindranath, D., Rodriguez, C. I. 2018; 46 (7): E722

  View details for DOI 10.1097/CCM.0000000000003058

  View details for Web of Science ID 000435290400023

  View details for PubMedID 29912121

• EXPLORING SOCIODEMOGRAPHIC AND CLINICAL CORRELATES OF OLDER ADULTS WITH OBSESSIVE-COMPULSIVE DISORDER: A REPORT FROM THE INTERNATIONAL COLLEGE OF OBSESSIVE-COMPULSIVE DISORDERS (ICOCS) Benatti, B., Dell'Osso, B., Rodriguez, C. I., Arici, C., Palazzo, C., Altamura, A., Hollander, E., Fineberg, N., Stein, D. J., Nicolini, H., Lanzagorta, N., Marazziti, D., Pallanti, S., Van Ameringen, M., Lochner, C., Karamustafalioglu, O., Hranov, L., Figee, M., Drummond, L., Grant, J., Denys, D., Zohar, J., Menchon, J. M. ELSEVIER SCIENCE BV. 2018: 765–66

  View details for DOI 10.1016/j.euroneuro.2017.10.007

  View details for Web of Science ID 000436626900016

• Clinical Implementation of Pharmacogenetic Decision Support Tools for Antidepressant Drug Prescribing. The American journal of psychiatry Zeier, Z., Carpenter, L. L., Kalin, N. H., Rodriguez, C. I., McDonald, W. M., Widge, A. S., Nemeroff, C. B. 2018: appiajp201817111282

  Abstract

  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 Kegeles, L., Stolz, E., Mao, X., Ojeil, N., Massuda, R., Pedrini, M., Bayatmokhtari, M., Slifstein, M., Abi-Dargham, A., Milak, M., Rodriguez, C., Chen, C., Shungu, D. 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 Linkovski, O., Shen, H., Zwerling, J., Filippou-Frye, M., Jo, B., Cordell, E., Cooper, T. B., Simpson, H. B., Burch, R. M., Moskal, J. R., Lee, F., Rodriguez, C. I. 2018; 79 (1)

  View details for DOI 10.4088/JCP.17l11824

  View details for PubMedID 29505186

• Challenges Testing Intranasal Ketamine in Obsessive-Compulsive Disorder (OCD) Rodriguez, C., Lapidus, K., Zwerling, J., Levinson, A., Mahnke, A., Steinman, S., Kalanthroff, E., Simpson, H. NATURE PUBLISHING GROUP. 2017: S128–S129

  View details for Web of Science ID 000416846301028

• Effect of a Novel NMDA Receptor Modulator, Rapastinel (formerly GLYX-13) in OCD: Proof-Of-Concept Rodriguez, C., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H., Burch, R., Moskal, J. ELSEVIER SCIENCE INC. 2017: S345–S346

  View details for DOI 10.1016/j.biopsych.2017.02.578

  View details for Web of Science ID 000400348700850

• Embracing Uncertainty as a First-Year Therapist Treating a Patient Who Has Obsessive-Compulsive Disorder. Psychiatric services Aston, P., Rodriguez, C. 2017; 68 (5): 433-434

  View details for DOI 10.1176/appi.ps.68501

  View details for PubMedID 28457206

• Challenges in Testing Intranasal Ketamine in Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY Rodriguez, C. I., Lapidus, K. B., Zwerling, J., Levinson, A., Mahnke, A., Steinman, S. A., Kalanthroff, E., Simpson, H. 2017; 78 (4): 466–67

  View details for DOI 10.4088/JCP.16cr11234

  View details for Web of Science ID 000405488000015

  View details for PubMedID 28448699

• 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). CNS spectrums Dell'Osso, B., Benatti, B., Arici, C., Palazzo, C., Altamura, A. C., Hollander, E., Fineberg, N., Stein, D. J., Nicolini, H., Lanzagorta, N., Marazziti, D., Pallanti, S., Van Ameringen, M., Lochner, C., Karamustafalioglu, O., Hranov, L., Figee, M., Drummond, L., Rodriguez, C. I., Grant, J., Denys, D., Menchon, J. M., Zohar, J. 2017: 1-8

  Abstract

  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

• Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13) in OCD: Proof-of-Concept Rodriguez, C., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H., Burch, R., Moskal, J. NATURE PUBLISHING GROUP. 2016: S334–S335

  View details for Web of Science ID 000440365600566

• Pilot Study of GLXY-13, an NMDAR Functional Glycine-Site Partial Agonist, in OCD Rodriguez, C. NATURE PUBLISHING GROUP. 2016: S62–S63

  View details for Web of Science ID 000440365600123

• Acceptability of treatments and services for individuals with hoarding behaviors JOURNAL OF OBSESSIVE-COMPULSIVE AND RELATED DISORDERS Rodriguez, C. I., Levinson, A., Patel, S. R., Rottier, K., Zwerling, J., Essock, S., Shuer, L., Frost, R. O., Simpson, H. B. 2016; 11: 1-8

  Abstract

  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

• Sips of Conflict AMERICAN JOURNAL OF PSYCHIATRY Wilkerson, E., Rodriguez, C. 2016; 173 (7): 664-664

  View details for DOI 10.1176/appi.ajp.2016.16030374

  View details for Web of Science ID 000378977000005

  View details for PubMedID 27363549

• Open-Label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. journal of clinical psychiatry Rodriguez, C. I., Levinson, A., Zwerling, J., Vermes, D., Simpson, H. B. 2016; 77 (5): 688-689

  View details for DOI 10.4088/JCP.15l10318

  View details for PubMedID 27249077

• An investigation of the role of intolerance of uncertainty in hoarding symptoms. Journal of affective disorders Wheaton, M. G., Abramowitz, J. S., Jacoby, R. J., Zwerling, J., Rodriguez, C. I. 2016; 193: 208-214

  Abstract

  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 Rodriguez, C. I., Wheaton, M., Zwerling, J., Steinman, S. A., Sonnenfeld, D., Galfalvy, H., Simpson, H. B. 2016; 77 (3): 408-409

  View details for DOI 10.4088/JCP.15l10138

  View details for PubMedID 27046314

• A pilot in vivo proton magnetic resonance spectroscopy study of amino acid neurotransmitter response to ketamine treatment of major depressive disorder. Molecular psychiatry Milak, M. S., Proper, C. J., Mulhern, S. T., Parter, A. L., Kegeles, L. S., Ogden, R. T., Mao, X., Rodriguez, C. I., Oquendo, M. A., Suckow, R. F., Cooper, T. B., Keilp, J. G., Shungu, D. C., Mann, J. J. 2016; 21 (3): 320–27

  Abstract

  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 Posner, J., Song, I., Lee, S., Rodriguez, C. I., Moore, H., Marsh, R., Blair Simpson, H. 2016

  Abstract

  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

• Pilot Trial of a Brief Course of Exposure-Based CBT in Extending IV Ketamine's Effects in OCD Rodriguez, C. NATURE PUBLISHING GROUP. 2015: S39

  View details for Web of Science ID 000366597700078

• Pilot Trial of a Brief Course of Exposure-Based CBT in Extending IV Ketamine's Effects in OCD Rodriguez, C., Wheaton, M., Zwerling, J., Steinman, S., Sonnenfeld, D., Galfalvy, H., Simpson, H. NATURE PUBLISHING GROUP. 2015: S117

  View details for Web of Science ID 000366597700227

• 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 Rodriguez, C. I., Zwerling, J., Sonnenfeld, D. 2015; 23 (6): 545-547

  View details for DOI 10.1016/j.jagp.2015.01.007

  View details for Web of Science ID 000354338100001

  View details for PubMedID 25966293

• 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 Foa, E. B., Simpson, H. B., Rosenfield, D., Liebowitz, M. R., Cahill, S. P., Huppert, J. D., Bender, J., McLean, C. P., Maher, M. J., Campeas, R., Hahn, C., Imms, P., Pinto, A., Powers, M. B., Rodriguez, C. I., Van Meter, P. E., Vermes, D., Williams, M. T. 2015; 76 (4): 440-446

  Abstract

  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 Rodriguez, C. 2015; 2 (8): 690–91

  View details for DOI 10.1016/S2215-0366(15)00328-4

  View details for PubMedID 26249298

• Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder A Randomized Clinical Trial JAMA PSYCHIATRY Simpson, H. B., Foa, E. B., Liebowitz, M. R., Huppert, J. D., Cahill, S., Maher, M. J., McLean, C. P., Bender, J., Marcus, S. M., Williams, M. T., Weaver, J., Vermes, D., Van Meter, P. E., Rodriguez, C. I., PowerS, M., Pinto, A., Imms, P., Hahn, C., Campeas, R. 2013; 70 (11): 1190-1198

  Abstract

  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 Rodriguez, C. I., Simpson, H. B., Liu, S., Levinson, A., Blanco, C. 2013; 201 (9): 795-801

  Abstract

  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 Rodriguez, C. I., Bender, J., Morrison, S., Mehendru, R., Tolin, D., Simpson, H. B. 2013; 33 (3): 444-447

  View details for DOI 10.1097/JCP.0b013e318290115e

  View details for Web of Science ID 000318871400028

  View details for PubMedID 23609401

• Public-Academic Partnerships A Rapid Small-Grant Program for Policy-Relevant Research: Motivating Public-Academic Partnerships PSYCHIATRIC SERVICES Rodriguez, C. I., Arbuckle, M. R., Simpson, H. B., Herman, D. B., Stroup, T. S., Skrobala, A. M., Sederer, L. I., Appel, A., Essock, S. M. 2013; 64 (2): 106-108

  Abstract

  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 Rodriguez, C. I., Herman, D., Alcon, J., Chen, S., Tannen, A., Essock, S., Simpson, H. B. 2012; 200 (1): 91-94

  Abstract

  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 Alcon, J., Glazier, K., Rodriguez, C. 2011; 168 (12): 1248-1248

  View details for DOI 10.1176/appi.ajp.2011.11091414

  View details for Web of Science ID 000297947400006

  View details for PubMedID 22193669

• Rapid Resolution of Obsessions After an Infusion of Intravenous Ketamine in a Patient With Treatment-Resistant Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY Rodriguez, C. I., Kegeles, L. S., Flood, P., Simpson, H. B. 2011; 72 (4): 567-569

  View details for DOI 10.4088/JCP.10l06653

  View details for Web of Science ID 000290012500020

  View details for PubMedID 21527129

• Minocycline Augmentation of Pharmacotherapy in Obsessive-Compulsive Disorder: An Open-Label Trial JOURNAL OF CLINICAL PSYCHIATRY Rodriguez, C. I., Bender, J., Marcus, S. M., Snape, M., Rynn, M., Simpson, H. B. 2010; 71 (9): 1247-1249

  View details for DOI 10.4088/JCP.09l05805blu

  View details for Web of Science ID 000282705700022

  View details for PubMedID 20923629

• Diagnosis and Treatment of a Patient With Both Psychotic and Obsessive-Compulsive Symptoms AMERICAN JOURNAL OF PSYCHIATRY Rodriguez, C. I., Corcoran, C., Simpson, H. B. 2010; 167 (7): 754-761

  View details for DOI 10.1176/appi.ajp.2009.09070997

  View details for Web of Science ID 000279429300008

  View details for PubMedID 20595428

• Personalized Intervention for Hoarders at Risk of Eviction PSYCHIATRIC SERVICES Rodriguez, C., Panero, L., Tannen, A. 2010; 61 (2): 205-205

  View details for Web of Science ID 000274160300020

  View details for PubMedID 20123831

• The Role of Culture in Psychodynamic Psychotherapy: Parallel Process Resulting From Cultural Similarities Between Patient and Therapist AMERICAN JOURNAL OF PSYCHIATRY Rodriguez, C. I., Cabaniss, D. L., Arbuckle, M. R., Oquendo, M. A. 2008; 165 (11): 1402-1406

  View details for DOI 10.1176/appi.ajp.2008.08020215

  View details for Web of Science ID 000260597000010

  View details for PubMedID 18981074

• Hindbrain rhombic lip is comprised of discrete progenitor cell populations allocated by Pax6 NEURON Landsberg, R. L., Awatramani, R. B., Hunter, N. L., Farago, A. F., DiPietrantonio, H. J., Rodriguez, C. I., Dymecki, S. M. 2005; 48 (6): 933-947

  Abstract

  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 NATURE GENETICS Awatramani, R., Soriano, P., Rodriguez, C., Mai, J. J., Dymecki, S. M. 2003; 35 (1): 70-75

  Abstract

  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.) Dymecki, S. M., Rodriguez, C. I., Awatramani, R. B. 2002; 185: 309-334

  View details for PubMedID 11768998

• Origin of the precerebellar system NEURON Rodriguez, C. I., Dymecki, S. M. 2000; 27 (3): 475-486

  Abstract

  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 Rodriguez, C. I., Buchholz, F., Galloway, J., Sequerra, R., Kasper, J., Ayala, R., Stewart, A. F., Dymecki, S. M. 2000; 25 (2): 139-140

  View details for Web of Science ID 000087459200007

  View details for PubMedID 10835623

• Short-wave cone signal in the red-green detection mechanism VISION RESEARCH Stromeyer, C. F., Chaparro, A., Rodriguez, C., Chen, D., Hu, E., Kronauer, R. E. 1998; 38 (6): 813-826

  Abstract

  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