Written Imaginal Exposure for Hoarding Disorder: A Preliminary Pilot Study.

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.

Prevalence and associations of poor mental health in the third year of COVID-19: U.S. population-based analysis from 2020 to 2022.

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.

Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans.

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.

Augmenting group hoarding disorder treatment with virtual reality discarding: A pilot study in older adults.

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.

Treatment-resistant OCD: Pharmacotherapies in adults.

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.

In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review.

OBJECTIVE: The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. METHODS: 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. RESULTS: 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." CONCLUSIONS: 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.

Anosognosia in hoarding disorder is predicted by alterations in cognitive and inhibitory control.

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.

Technology and Mental Health: State of the Art for Assessment and Treatment.

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.

Valence processing alterations in SAPAP3 knockout mice and human OCD.

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.

The role of gender in a large international OCD sample: A Report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) Network.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. DISCUSSION/CONCLUSIONS: 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.

Rising to the Challenge: Strategies to Support Latinas and Other Women of Color in Science and Medicine.

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 Invited 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 science, technology, engineering, mathematics, and medicine (STEMM) 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.

A Spanish translation of the Hoarding Rating Scale: Differential item functioning and convergent validity.

Hoarding disorder (HD) involves extreme difficulties discarding possessions and significant clutter in living areas. Although hoarding occurs worldwide, cross-cultural research remains in nascent stages, hampered in part by a lack of validated measures in non-English languages. We aimed to validate a Spanish translation of the Hoarding Rating Scale (HRS), a widely used measure of core HD symptoms. Our sample (N=736) included participants responding in English (n=548; 45.4% female; 7.9% Latinx) or Spanish (n=188; 46.3% female; 79.9% Latinx) to questionnaires via Amazon's Mechanical Turk. An item response theory (IRT) approach was used to test differential item functioning (DIF) of the English and Spanish HRS. We also examined convergent validity of each language version with other HD. Initial comparisons revealed that hoarding symptoms were elevated in the Spanish-speaking sample compared to the English-speaking sample. DIF tests flagged the clutter item for potential bias (McFadden's ß=.069), but closer examination revealed that the impact was negligible. The Spanish HRS was significantly linked with other hoarding measures (Saving Inventory-Revised: ß=.497, p<.001; Obsessive-Compulsive Inventory-Revised-Hoarding Subscale: ß=.329, p=.008), controlling for mood, anxiety, stress, and non-hoarding OCD symptoms. However, the Spanish HRS was not significantly associated with Clutter Image Rating scores. Findings supported the utility of the HRS to measure of HD symptoms in Spanish speakers, though cross-linguistic assessment of clutter and the applicability of clinical cutoffs with Spanish-speaking samples merits further study.

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice.

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.

Psychedelics and Psychedelic-Assisted Psychotherapy.

(Reprinted with permission from The American Journal of Psychiatry 2020; 177:391-410).

Prevalence and correlates of current suicide risk in an international sample of OCD adults: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network and Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology.

INTRODUCTION: Obsessive-compulsive disorder (OCD), characterized by repetitive anxiety-inducing intrusive thoughts and compulsive behaviors, is associated with higher suicide ideation and suicide attempts than the general population. This study investigates the prevalence and the correlates of current suicide risk in adult outpatients in an international multisite cross-sectional sample of OCD outpatients. METHODS: Data were derived from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network's cross-sectional data set (N = 409). Current suicide risk (assessed by Item C of the MINI) and diagnoses of psychiatric disorders were based on DSM-IV. Chi-squared test for categorical variables and t-test for continuous variables were used to make statistical inferences about main features associated with current suicide risk. P < .05 was considered as statistically significant. RESULTS: The prevalence of current suicidal risk was 15.9%, with equal likelihood in sociodemographic variables, including age and gender. Increased rates of major depression and generalized anxiety disorder were associated to higher current suicide risk. Current suicide risk was also associated with higher severity of OCD, depressive comorbidity, and higher levels of disability. There were no significant differences in treatment correlates-including type of treatment and psychiatric hospitalizations-between the groups of individuals with and without current suicide risk. CONCLUSION: Our findings suggest that current suicide risk is common in patients with OCD and associated with various forms of pathology. Our work also provides further empirical data to support what is already known clinically: a worse clinical picture characterized by a high severity of OCD, high distress related to obsessions and compulsions, and the presence of comorbidities such as major depression and generalized anxiety disorder should be considered as relevant risk factors for suicide risk.

Specialty knowledge and competency standards for pharmacotherapy for adult obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) affects approximately one person in 40 and causes substantial suffering. Evidence-based treatments can benefit many; however, optimal treatment can be difficult to access. Diagnosis is frequently delayed, and pharmacological and psychotherapeutic interventions often fail to follow evidence-based guidelines. To ameliorate this distressing situation, the International OCD Accreditation Task Force of the Canadian Institute for Obsessive-Compulsive Disorders has developed knowledge and competency standards for specialized treatments for OCD through the lifespan. These are foundational to evidence-based practice and will form the basis for upcoming ATF development of certification/accreditation programs. Here, we present specialty standards for the pharmacological treatment of adult OCD. We emphasize the importance of integrating pharmacotherapy with clear diagnosis, appreciation of complicating factors, and evidence-based cognitive behavioral therapy. Clear evidence exists to inform first- and second-line pharmacological treatments. In disease refractory to these initial efforts, multiple strategies have been investigated, but the evidence is more equivocal. These standards summarize this limited evidence to give the specialist practitioner a solid basis on which to make difficult decisions in complex cases. It is hoped that further research will lead to development of a clear, multi-step treatment algorithm to support each step in clinical decision-making.