Carolyn Rodriguez's Profile
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This study explores whether a facilitated peer support group called Buried in Treasures (BIT) and a virtual reality decluttering practice can help individuals with clutter challenges.

Stanford is currently not accepting patients for this trial. For more information, please contact Thasveen Sandhu, 650-724-8912.

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Abstract

OBJECTIVE: The Buried in Treasures (BIT) workshop is a promising treatment for hoarding disorder (HD), though many participants struggle with home uncluttering. This randomized waitlist-controlled trial investigated the efficacy of a version of BIT, augmented with in-home uncluttering practice (BIT+).METHOD: Adults (N=41) with hoarding disorder were recruited from the community and randomly assigned to BIT+or waitlist. BIT+consisted of 16 sessions of the BIT workshop and 10 uncluttering home visits over 18 weeks. Outcome measures included the Saving Inventory-Revised (self-report) and the Clutter Image Rating Scale (self and independent evaluator rated). Between group repeated measures analyses using general linear modeling examined the effect of BIT+vs waitlist control on hoarding symptoms after 18 weeks. Within group analyses examined pre-post effects for all BIT+participants combined after 18 weeks.RESULTS: After 18 weeks, BIT+participants benefited significantly more than waitlist controls on hoarding severity with large effect size (Cohen's d=1.5, p<.001). BIT+ was also associated with improvement reductions in hoarding symptoms, clutter, and functional impairment.CONCLUSIONS: The BIT+intervention offers promise as a treatment option for hoarding. Adding in-home uncluttering practice may incrementally improve discarding practices. Future controlled trials are warranted.

View details for DOI 10.1016/j.jpsychires.2024.05.055

View details for PubMedID 38843580

Abstract

ABSTRACT: Hoarding disorder (HD) is marked by difficulty discarding possessions. Many refuse treatment or drop out, which may be due to treatment's incorporation of in-home decluttering, which is feared and avoided. Thus, strategies to prepare patients for decluttering/discarding are needed. Imaginal exposure (IE), or imagining one's worst fears about discarding, could be one such strategy. This pilot preliminarily tested a short-duration IE intervention compared with a control intervention. Over 3 days, adults diagnosed with HD (n = 32) were randomly assigned to either write about and imagine their worst fears about discarding (IE condition) or a neutral topic (control writing [CW] condition). The IE condition showed significant improvements in HD symptoms from preintervention to 1-week follow-up, with medium to large effects; however, the CW condition did as well. Comparing change scores between conditions, the IE condition's improvements were not significantly different than the CW condition's. Overall, IE was helpful in improving HD symptoms, but this pilot did not indicate that it was more helpful than CW. This raises important questions about possible demand characteristics, placebo effects, or regression to the mean, and it has implications for the design and methodology of other studies assessing IE's utility.

View details for DOI 10.1097/NMD.0000000000001719

View details for PubMedID 38598729

Abstract

BACKGROUND: Poorer mental health was found early in the COVID-19 pandemic, yet mental health in the third year of COVID-19 has not been assessed on a general adult population level in the United States.METHODS: We used a nationally representative cross-sectional survey (Health Information National Trends Survey, HINTS 5 2020 n=3,865 and HINTS 6 2022 n=6,252). The prevalence of poor mental health was examined using a Patient Health Questionnaire-4 scale in 2020 and 2022. We also investigated the factors associated with poor mental health in 2022 using a weighted multivariable logistic regression adjusting for sociodemographic and health status characteristics to obtain the odds ratio (OR).OUTCOMES: The prevalence of poor mental health in adults increased from 2020 to 2022 (31.5% vs 36.3%, p=0.0005). U.S. adults in 2022 were 1.28 times as likely to have poor mental health than early in the pandemic. Moreover, individuals with food insecurity, housing instability, and low income had greater odds of poor mental health (ORs=1.78-2.55). Adults who were females, non-Hispanic Whites, or age 18-64 years were more likely to have poor mental health (ORs=1.46-4.15).INTERPRETATION: Mental health of U.S. adults worsened in the third year of COVID-19 compared to the beginning of the pandemic.

View details for DOI 10.1016/j.psychres.2023.115622

View details for PubMedID 38006717

Abstract

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, https://www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5000 richly phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

View details for DOI 10.1002/ajmg.b.32962

View details for PubMedID 37946624

Abstract

Ketamine commonly and rapidly induces dissociative and other altered states of consciousness (ASCs) in humans. However, the neural mechanisms that contribute to these experiences remain unknown. We used functional neuroimaging to engage key regions of the brain's affective circuits during acute ketamine-induced ASCs within a randomized, multi-modal, placebo-controlled design examining placebo, 0.05 mg/kg ketamine, and 0.5 mg/kg ketamine in nonclinical adult participants (NCT03475277). Licensed clinicians monitored infusions for safety. Linear mixed effects models, analysis of variance, t-tests, and mediation models were used for statistical analyses. Our design enabled us to test our pre-specified primary and secondary endpoints, which were met: effects of ketamine across dose conditions on (1) emotional task-evoked brain activity, and (2) sub-components of dissociation and other ASCs. With this design, we also could disentangle which ketamine-induced affective brain states are dependent upon specific aspects of ASCs. Differently valenced ketamine-induced ASCs mediated opposing effects on right anterior insula activity. Participants experiencing relatively higher depersonalization induced by 0.5 mg/kg of ketamine showed relief from negative brain states (reduced task-evoked right anterior insula activity, 0.39 SD). In contrast, participants experiencing dissociative amnesia showed an exacerbation of insula activity (0.32 SD). These results in nonclinical participants may shed light on the mechanisms by which specific dissociative states predict response to ketamine in depressed individuals.

View details for DOI 10.1038/s41467-023-42141-5

View details for PubMedID 37857620

View details for PubMedCentralID 5126726

Abstract

Hoarding disorder is common and debilitating, especially in older adults, and novel treatment approaches are needed. Many current treatments emphasize skills related to discarding and decision-making about possessions, which can be practiced in the patient's home. However in many cases, in-home visits are unfeasible, or real-life discarding is too difficult. Virtual reality (VR) offers the ability to create a virtual "home" including 3D scans of the patient's actual possessions that can be moved or discarded. VR discarding is an alternative to in-home visits and an approach that provides a stepping stone to real-life discarding. VR has been successfully utilized to treat many disorders but tested minimally in hoarding disorder. In nine older adults with hoarding disorder, we tested an 8-week VR intervention administered to augment a 16-week Buried in Treasures group treatment. Individualized VR rooms were uniquely modeled after each patient's home. During clinician-administered VR sessions, patients practiced sorting and discarding their virtual possessions. The intervention was feasible to administer. Open-ended participant responses, examined by two independent evaluators, indicated that VR sessions were well-tolerated and that participants found them useful, with nearly all participants noting that VR helped them increase real-life discarding. Self-reported hoarding symptoms decreased from baseline to close, with seven of the nine participants showing reliable improvement in this timeframe and none showing deterioration. Results from this exploratory pilot study suggest that VR is a feasible way to simulate an at-home sorting and discarding experience in a manner that may augment skills acquisition. It remains an open question whether VR discarding practice yields greater improvement than existing treatments. VR for this population merits further clinical investigation.

View details for DOI 10.1016/j.jpsychires.2023.08.002

View details for PubMedID 37716272

Abstract

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics. In this study protocol paper, we describe the Latin American Trans-ancestry INitiative for OCD genomics (LATINO, www.latinostudy.org). LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. In this project, we will utilize trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. We will also capitalize on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. Additionally, LATINO will help elucidate the diversity of the clinical presentations of OCD across cultures through various trainings developed and offered in collaboration with Latin American investigators. We believe this study will advance the important goal of global mental health discovery and equity.

View details for DOI 10.1101/2023.02.23.23286373

View details for PubMedID 37131804

View details for PubMedCentralID PMC10153323

Abstract

Insight impairment contributes significantly to morbidity in psychiatric disorders. The neurologic concept of anosognosia, reflecting deficits in metacognitive awareness of illness, is increasingly understood as relevant to psychopathology, but has been little explored in psychiatric disorders other than schizophrenia. We explored anosognosia as an aspect of insight impairment in n = 71 individuals with DSM-5 hoarding disorder. We used a standardized clutter severity measure to assess whether individuals with hoarding disorder underreport home clutter levels relative to independent examiners. We then explored whether underreporting, as a proxy for anosognosia, is predicted by clinical or neurocognitive behavioral measures. We found that individuals with hoarding disorder underreport their clutter, and that underreporting is predicted by objective severity of clutter. In an n = 53 subset of participants, we found that underreporting is predicted by altered performance on tests of cognitive control and inhibition, specifically Go/No-Go and Stroop tests. The relation of underreporting to objective clutter, the cardinal symptom of hoarding disorder, suggests that anosognosia may reflect core pathophysiology of the disorder. The neurocognitive predictors of clutter underreporting suggest that anosognosia in hoarding disorder shares a neural basis with metacognitive awareness deficits in other neuropsychiatric disorders and that executive anosognosia may be a transdiagnostic manifestation of psychopathology.

View details for DOI 10.1038/s41598-022-25532-4

View details for PubMedID 36526652

Abstract

Serotonin reuptake inhibitor (SRI) medications are well established as first-line pharmacotherapeutic treatment for Obsessive-Compulsive Disorder (OCD). However, despite the excellent safety profile and demonstrated efficacy of these medications, a substantial proportion of individuals with OCD fail to attain sufficient benefit from SRIs. In this narrative review, we discuss clinical features of OCD that have been associated with poorer response to SRIs, and we present pharmacotherapeutic interventions that have been explored as augmenting or alternative treatments for treatment-resistant OCD. We additionally highlight non-SRI interventions for OCD that are currently under investigation. Pharmacotherapeutic interventions were identified via expert consensus. To assess the evidence base for individual pharmacotherapies, targeted searches for relevant English-language publications were performed on standard biomedical research databases, including MEDLINE. Information relevant to ongoing registered clinical trials in OCD was obtained by search of ClinicalTrials.gov. Pharmacotherapies are grouped for review in accordance with the general principles of Neuroscience-based Nomenclature (NbN). Clinical features of OCD that may suggest poorer response to SRI treatment include early age of onset, severity of illness, duration of untreated illness, and the presence of symmetry/ordering or hoarding-related symptoms. Based on evolving pathophysiologic models of OCD, diverse agents engaging serotonin, dopamine, norepinephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Medications with dopamine antagonist activity remain the most robustly evidence-based of augmenting interventions, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Interventions targeting glutamatergic and anti-inflammatory pathways are less well evidenced, but may offer more favorable benefit to risk profiles. Ongoing research should explore whether specific interventions may benefit individuals with particular features of treatment-resistant OCD.

View details for DOI 10.1016/j.comppsych.2022.152352

View details for PubMedID 36368186

Abstract

Technology is ubiquitous in society and is now being extensively used in mental health applications. Both assessment and treatment strategies are being developed and deployed at a rapid pace. The authors review the current domains of technology utilization, describe standards for quality evaluation, and forecast future developments. This review examines technology-based assessments of cognition, emotion, functional capacity and everyday functioning, virtual reality approaches to assessment and treatment, ecological momentary assessment, passive measurement strategies including geolocation, movement, and physiological parameters, and technology-based cognitive and functional skills training. There are many technology-based approaches that are evidence based and are supported through the results of systematic reviews and meta-analyses. Other strategies are less well supported by high-quality evidence at present, but there are evaluation standards that are well articulated at this time. There are some clear challenges in selection of applications for specific conditions, but in several areas, including cognitive training, randomized clinical trials are available to support these interventions. Some of these technology-based interventions have been approved by the U.S. Food and Drug administration, which has clear standards for which types of applications, and which claims about them, need to be reviewed by the agency and which are exempt.

View details for DOI 10.1176/appi.ajp.21121254

View details for PubMedID 36200275

Abstract

Abnormalities in valence processing - the processing of aversive or appetitive stimuli - may be an underrecognized component of obsessive-compulsive disorder (OCD). Preclinical rodent models have been critical in furthering pathophysiological understanding of OCD, yet there is a dearth of investigations examining whether rodent models of compulsive behavior show alterations in valence systems congruent with those seen in individuals with OCD. In this study, we sought to assess valence processing in a preclinical rodent model of compulsive behavior, the SAPAP3 knockout (KO) mouse model, and compare our preclinical findings to similar behavioral phenomena in OCD patients. In SAPAP3 KO mice, we used auditory fear conditioning and extinction to examine alterations in negative valence processing and reward-based operant conditioning to examine alterations in positive valence processing. We find that SAPAP3 KO mice show evidence of heightened negative valence processing through enhanced fear learning and impaired fear extinction. SAPAP3 KO mice also show deficits in reward acquisition and goal-directed behavior, suggesting impaired positive valence processing. In OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence). We find similar trends towards enhanced negative and impaired positive valence processing in OCD patients. Overall, our results reveal valence processing abnormalities in a preclinical rodent model of compulsive behavior similar to those seen in OCD patients, with implications for valence processing alterations as novel therapeutic targets across a translational research spectrum.

View details for DOI 10.1016/j.jpsychires.2022.05.024

View details for PubMedID 35661523

Abstract

OBJECTIVE: The United States is in the midst of rapidly changing laws regarding cannabis. The increasing availability of cannabis for recreational and medical use requires that mental health clinicians be knowledgeable about evidence to be considered when counseling both patients and colleagues. In this review, the authors outline the evidence from randomized double-blind placebo-controlled trials for therapeutic use of cannabinoids for specific medical conditions and the potential side effects associated with acute and chronic cannabis use.METHODS: Searches of PubMed and PsycInfo were conducted for articles published through July 2021 reporting on "cannabis" or "cannabinoids" or "medicinal cannabis." Additional articles were identified from the reference lists of published reviews. Articles that did not contain the terms "clinical trial" or "therapy" in the title or abstract were not reviewed. A total of 4,431 articles were screened, and 841 articles that met criteria for inclusion were reviewed by two or more authors.RESULTS: There are currently no psychiatric indications approved by the U.S. Food and Drug Administration (FDA) for cannabinoids, and there is limited evidence supporting the therapeutic use of cannabinoids for treatment of psychiatric disorders. To date, evidence supporting cannabinoid prescription beyond the FDA indications is strongest for the management of pain and spasticity.CONCLUSIONS: As cannabinoids become more available, the need for an evidence base adequately evaluating their safety and efficacy is increasingly important. There is considerable evidence that cannabinoids have a potential for harm in vulnerable populations such as adolescents and those with psychotic disorders. The current evidence base is insufficient to support the prescription of cannabinoids for the treatment of psychiatric disorders.

View details for DOI 10.1176/appi.ajp.2021.21030320

View details for PubMedID 34875873

Abstract

Although the number of Hispanic/Latina women earning medical degrees has increased in recent years, the article by Anaya and colleagues in this issue highlights their stark underrepresentation in the U.S. physician workforce. In this commentary, the authors provide context on proposed drivers of underrepresentation, including bias, discrimination, harassment, and other structural barriers, which are amplified for women with multiple minoritized identities. They summarize the 2020 National Academies of Sciences, Engineering, and Medicine recommendations for supporting women in STEMM (science, technology, engineering, mathematics, and medicine) fields, including committed leadership, dedicated financial and human resources, data-driven accountability, and use of an intersectional approach to address the challenges faced by individuals who encounter multiple forms of bias and discrimination. The authors also provide additional recommendations and highlight innovative new National Institutes of Health funding opportunities to promote diversity in the scientific workforce. They argue that more research is needed to identify and best implement institutional practices that increase representation and retention of Latina women and other women with minoritized identities in STEMM fields.

View details for DOI 10.1097/ACM.0000000000004558

View details for PubMedID 34879010

Abstract

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine's therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity reduced compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. Finally, we demonstrate that ketamine blocks the exacerbation of grooming in KO mice caused by optogenetically inhibiting fronto-striatal activity. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine's therapeutic effects in OCD.

View details for DOI 10.1038/s41467-021-26247-2

View details for PubMedID 34654803

Abstract

"Mr. A," a 24-year-old man, presents for evaluation of worsening depression. He describes a history of depression since adolescence, although he notes that he suffered a troubled childhood, including emotional neglect. He believes a recent breakup and having been denied a promotion precipitated this episode. "I'm sleeping all the time, and my body feels heavy," he adds. He also reports increased appetite, weight gain, and "urges to cut, which I have not done in years." However, he remains social and actively involved in several hobbies. He discontinued bupropion and escitalopram in the past because of "terrible headaches and irritability." Initially, you consider starting lamotrigine. However, your office recently implemented a clinical decision support system that recommends a trial of phenelzine. The patient's symptoms remit entirely on the medication suggested by the system. Curious as to how the system decided on this treatment, you download several papers on its development.

View details for DOI 10.1176/appi.ajp.2020.20030250

View details for PubMedID 34080891

Abstract

Hoarding disorder (HD), characterized by difficulty parting with possessions and functionally impairing clutter, affects 2-6% of the population. Originally considered part of Obsessive-Compulsive Disorder (OCD), HD became a distinct diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. While sleep impacts OCD, little is known about sleep in HD. As HD patients often report poor sleep in clinical settings, understanding global subjective sleep quality and disturbances may lead to novel therapeutic targets. To address this gap, the authors used a sample of convenience: an existing data set designed to screen research study eligibility and explore the psychopathology and phenomenology of OCD and HD. The data set included information collected from individuals with HD (n=38), OCD (n=26), and healthy participants (n=22) about insomnia, sleep quality, and mood using interviews and structured instruments including the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Depression Anxiety Stress Scales (DASS). In this data set, HD and OCD groups reported significantly greater insomnia symptoms and poorer sleep quality compared with healthy controls while controlling for depression, age, and gender. A sizable minority of HD and OCD individuals met criteria for comorbid sleep disorders. OCD and HD groups differed in delayed sleep phase prevalence. To our knowledge, this is the first study examining subjective sleep quality and insomnia in HD as compared to healthy individuals and those with OCD, while controlling for relevant clinical characteristics. Given that there are evidence-based treatments for insomnia and other sleep disorders, our study raises the possibility that treatment interventions targeting sleep may improve HD outcomes.

View details for DOI 10.1016/j.jpsychires.2020.10.044

View details for PubMedID 33309063

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

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

View details for PubMedCentralID PMC3799067

Abstract

The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials.A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included.A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis."There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.

View details for DOI 10.1176/appi.ajp.21100992

View details for PubMedID 36475375

Abstract

Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD.Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS).Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity.Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.

View details for DOI 10.1016/j.comppsych.2022.152315

View details for PubMedID 35483201

Abstract

Major depressive disorder is a common psychiatric disorder associated with marked suffering, morbidity, mortality, and cost. The World Health Organization projects that by 2030, major depression will be the leading cause of disease burden worldwide. While numerous treatments for major depression exist, many patients do not respond adequately to traditional antidepressants. Thus, more effective treatments for major depression are needed, and targeting certain hormonal systems is a conceptually based approach that has shown promise in the treatment of this disorder. A number of hormones and hormone-manipulating compounds have been evaluated as monotherapies or adjunctive treatments for major depression, with therapeutic actions attributable not only to the modulation of endocrine systems in the periphery but also to the CNS effects of hormones on non-endocrine brain circuitry. The authors describe the physiology of the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary thyroid (HPT), and hypothalamic-pituitary-gonadal (HPG) axes and review the evidence for selected hormone-based interventions for the treatment of depression in order to provide an update on the state of this field for clinicians and researchers. The review focuses on the HPA axis-based interventions of corticotropin-releasing factor antagonists and the glucocorticoid receptor antagonist mifepristone, the HPT axis-based treatments of thyroid hormones (T3 and T4), and the HPG axis-based treatments of estrogen replacement therapy, the progesterone derivative allopregnanolone, and testosterone. While some treatments have largely failed to translate from preclinical studies, others have shown promising initial results and represent active fields of study in the search for novel effective treatments for major depression.

View details for DOI 10.1176/appi.ajp.2020.19080848

View details for PubMedID 32456504

Abstract

OBJECTIVE: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.METHODS: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on "psilocybin," "lysergic acid diethylamide," "LSD," "ayahuasca," "3,4-methylenedioxymethamphetamine," and "MDMA," in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms "clinical trial," "therapy," or "imaging" in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care.RESULTS: The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as "breakthrough therapies" for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuasca is observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.CONCLUSIONS: Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.

View details for DOI 10.1176/appi.ajp.2019.19010035

View details for PubMedID 32098487

Abstract

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.

View details for DOI 10.1097/YIC.0000000000000314

View details for PubMedID 32433254

Abstract

Obsessive-compulsive disorder (OCD), characterized by repetitive thoughts (obsessions) and behaviors (compulsions), is a leading cause of health-related disability in the world. Various kinds of obsessions and compulsions exist and tend to co-occur in dimensions (e.g., doubting/checking, symmetry/ordering, contamination/cleaning). Cognitive-behavioral therapy (CBT) consisting of exposure and response (ritual) prevention (ERP) is arguably the safest and most efficacious treatment for OCD. ERP involves exposing OCD patients to stimuli that provoke obsessions while coaching them to not ritualize. There is increasing evidence to suggest that the specific symptom dimensions of OCD have unique correlates and different responsiveness to ERP. Although many patients respond to ERP, only a subset achieve minimal symptoms. Given the challenges that may arise in ERP treatment of specific OCD dimensions, there has been increasing interest in examining OCD with relationship-related themes that focus on the romantic relationship or partner. In this case report, we present a case of an adult with OCD containing relationship themes and highlight ERP adaptations we utilized to improve his treatment course.

View details for DOI 10.1891/0889-8391.33.3.185

View details for PubMedID 32746426

Abstract

IntroductionBipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.METHODS: We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.RESULTS: Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).CONCLUSION: These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.

View details for DOI 10.1017/S1092852919001068

View details for PubMedID 31131775

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 PubMedID 30419524

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 PubMedID 30278789

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 PubMedID 29690793

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

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

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

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

View details for PubMedCentralID PMC4758914

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

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

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

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

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

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

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

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

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

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