Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study protocol.

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.

Habitual versus affective motivations in obsessive-compulsive disorder and alcohol use disorder.

OBJECTIVE: To (1) confirm whether the Habit, Reward, and Fear Scale is able to generate a 3-factor solution in a population of obsessive-compulsive disorder and alcohol use disorder (AUD) patients; (2) compare these clinical groups in their habit, reward, and fear motivations; and (3) investigate whether homogenous subgroups can be identified to resolve heterogeneity within and across disorders based on the motivations driving ritualistic and drinking behaviors. METHODS: One hundred and thirty-four obsessive-compulsive disorder (n = 76) or AUD (n = 58) patients were assessed with a battery of scales including the Habit, Reward, and Fear Scale, the Yale-Brown Obsessive-Compulsive Scale, the Alcohol Dependence Scale, the Behavioral Inhibition/Activation System Scale, and the Urgency, (lack of ) Premeditation, (lack of ) Perseverance, Sensation Seeking, and Positive Urgency Impulsive Behavior Scale. RESULTS: A 3-factor solution reflecting habit, reward, and fear subscores explained 56.6% of the total variance of the Habit, Reward, and Fear Scale. Although the habit and fear subscores were significantly higher in obsessive-compulsive disorder (OCD) and the reward subscores were significantly greater in AUD patients, a cluster analysis identified that the 3 clusters were each characterized by differing proportions of OCD and AUD patients. CONCLUSIONS: While affective (reward- and fear-driven) and nonaffective (habitual) motivations for repetitive behaviors seem dissociable from each other, it is possible to identify subgroups in a transdiagnostic manner based on motivations that do not match perfectly motivations that usually described in OCD and AUD patients.

Fear driven compulsive behaviour is associated with worse long-term outcome in obsessive-compulsive disorder.

OBJECTIVES: In this retrospective study of patients with obsessive-compulsive disorder (OCD), we assessed the relationship between different motivational drivers of compulsive behaviours and the response to naturalistic treatments (based mostly on high dose serotonin reuptake inhibitors [SRIs]). METHODS: Seventy-six OCD patients were assessed with a structured diagnostic interview; the Habit, Reward and Fear Scale-Revised (HRFS-R); the Yale-Brown Obsessive-Compulsive Scale (YBOCS); the Beck Depression Inventory (BDI); and the OCD Retrospective Assessment of Treatment Response (RATS), which includes information on SRIs administration (e.g., dose and duration of their use), augmentation strategies (such as antipsychotic use or exposure and response prevention intervention), and pre-treatment YBOCS scores. Patients were naturalistically followed up for a mean of 7.28 (SD 5.51) years. RESULTS: Analysis revealed that the fear subscore of the HRFS was the only significant predictor (among a detailed battery of demographic, clinical and treatment factors) independently associated with greater delta (pre-treatment minus post-treatment) YBOCS scores. CONCLUSIONS: In contrast to predictions (based on existing models), poorer treatment response was not associated with increased habit scores in the HRFS. Future longitudinal studies are needed to confirm whether increased fear as a driver for ritualistic behaviours is able to predict worse outcomes in OCD samples.

A study on the correlates of habit-, reward-, and fear-related motivations in alcohol use disorder.

OBJECTIVE: We assessed self-reported drives for alcohol use and their impact on clinical features of alcohol use disorder (AUD) patients. Our prediction was that, in contrast to "affectively" (reward or fear) driven drinking, "habitual" drinking would be associated with worse clinical features in relation to alcohol use and higher occurrence of associated psychiatric symptoms. METHODS: Fifty-eight Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol abuse patients were assessed with a comprehensive battery of reward- and fear-based behavioral tendencies. An 18-item self-report instrument (the Habit, Reward and Fear Scale; HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) motivations for alcohol use. To characterize clinical and demographic measures associated with habit, reward, and fear, we conducted a partial least squares analysis. RESULTS: Habitual alcohol use was significantly associated with the severity of alcohol dependence reflected across a range of domains and with lower number of detoxifications across multiple settings. In contrast, reward-driven alcohol use was associated with a single domain of alcohol dependence, reward-related behavioral tendencies, and lower number of detoxifications. CONCLUSION: These results seem to be consistent with a shift from goal-directed to habit-driven alcohol use with severity and progression of addiction, complementing preclinical work and informing biological models of addiction. Both reward-related and habit-driven alcohol use were associated with lower number of detoxifications, perhaps stemming from more benign course for the reward-related and lack of treatment engagement for the habit-related alcohol abuse group. Future work should further explore the role of habit in this and other addictive disorders, and in obsessive-compulsive related disorders.

Unpacking the role of self-reported compulsivity and impulsivity in obsessive-compulsive disorder.

OBJECTIVE: We aimed to determine whether individuals with obsessive-compulsive disorder (OCD) and demographically matched healthy individuals can be clustered into distinct clinical subtypes based on dimensional measures of their self-reported compulsivity (OBQ-44 and IUS-12) and impulsivity (UPPS-P). METHODS: Participants (n=217) were 103 patients with a clinical diagnosis of OCD; 79 individuals from the community who were "OCD-likely" according to self-report (Obsessive-Compulsive Inventory-Revised scores equal or greater than 21); and 35 healthy controls. All data were collected between 2013 and 2015 using self-report measures that assessed different aspects of compulsivity and impulsivity. Principal component analysis revealed two components broadly representing an individual's level of compulsivity and impulsivity. Unsupervised clustering grouped participants into four subgroups, each representing one part of an orthogonal compulsive-impulsive phenotype. RESULTS: Clustering converged to yield four subgroups: one group low on both compulsivity and impulsivity, comprised mostly of healthy controls and demonstrating the lowest OCD symptom severity; two groups showing roughly equal clinical severity, but with opposing drivers (i.e., high compulsivity and low impulsivity, and vice versa); and a final group high on both compulsivity and impulsivity and recording the highest clinical severity. Notably, the largest cluster of individuals with OCD was characterized by high impulsivity and low compulsivity. Our results suggest that both impulsivity and compulsivity mediate obsessive-compulsive symptomatology. CONCLUSIONS: Individuals with OCD can be clustered into distinct subtypes based on measures of compulsivity and impulsivity, with the latter being found to be one of the more defining characteristics of the disorder. These dimensions may serve as viable and novel treatment targets.

Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder.

Aims To determine the rates and associated illness characteristics of obsessive-compulsive disorder (OCD) patients who describe their symptoms as either rewarding or habitual. METHODS: Seventy-three treatment-seeking OCD patients had their dominant compulsive behavior assessed with a structured interview (the Temporal Impulsive-Compulsive Scale-Revised) to track the progression of rewarding (ie, gain in positive affect), aversive (ie, decrease in negative affect), and neutral (or non-affective) states and a self-report scale (the Self-Report Habit Index) to evaluate their habitual features. Additional measures included structured diagnostic interviews for axis I and II disorders, measures of OCD symptoms severity, and a battery of instruments to comprehensively assess relevant aspects of sensitivity to reward and fear. RESULTS: Almost half (49%) of our OCD patients (particularly washers) endorsed that they anticipated obtaining a reward (ie, positive affect) from the enactment of their dominant compulsive behavior. Washers stood out in that their positive affects during and after compulsive behaviors were highly (and positively) correlated with duration of illness. In contrast, habit strength did not differ between washers, checkers, and arrangers, although it also correlated with duration of illness among checkers. Furthermore, the severity of OCD and comorbidity with impulse control disorders predicted up to 35% of the variance in the habit strength of OCD behaviors. CONCLUSION: Compulsive washing may be more clearly characterized by problems in reward processing. In contrast, duration of checking, severity of OCD, and comorbidity with impulse control disorders shape compulsive behaviors by imparting them with habitual tendencies.

Hoarding pet animals in obsessive-compulsive disorder.

BACKGROUND: Although severe hoarding symptoms have been considered rare among obsessive-compulsive disorder (OCD) samples, the prevalence of animal hoarding in OCD is unknown. To help clarifying this issue, we searched for cases of animal hoarding among patients attending a university OCD clinic (n=420). METHODS: Chart review. RESULTS: Only two patients from our sample exhibited animal hoarding (<0.5%) and only one of them presented additional obsessive-compulsive symptoms. Both cases also collected inanimate objects, presented low insight, exhibited poor response to serotonin reuptake inhibitors and did not adhere to therapy. CONCLUSIONS: There seems to be a lack of relationship between animal hoarding and OCD. However, further studies with larger numbers of patients are needed to better define their psychopathological profile and more appropriate nosological insertion.

Hatred of sounds: misophonic disorder or just an underreported psychiatric symptom?

BACKGROUND: Misophonia, or selective sound sensitivity syndrome, is a preoccupation with or aversion to certain types of sounds that evokes feelings of irritability, disgust, or anger. Recently, it has been suggested that misophonia is a discrete clinical entity deserving of its own place in psychiatric diagnostic manuals. In this paper, we describe 3 patients whose misophonia could be attributed to different underlying primary psychiatric disorders. METHODS: Case series report. RESULTS: In these patients, we argue that misophonia is better described as a symptom of a) obsessive-compulsive disorder, b) generalized anxiety disorder, and c) schizotypal personality disorder. CONCLUSIONS: The nosological status of misophonia remains a matter of debate. Patients who exhibit misophonia as a major complaint should be assessed for other conditions. Further studies on the prevalence, natural history, and additional features of misophonia are needed.

Habit-, reward- and fear-related motivations in alcohol use disorder: A one-year prospective study.

OBJECTIVE: Cross-sectional studies show that habitual use of alcohol is associated with severity of alcohol dependence reflected across a range of domains and lower number of detoxifications in multiple settings. In this study, we investigated whether alcohol use disorder (AUD) patients with greater habitual use of alcohol at baseline showed worse outcomes after one year of follow-up. METHODS: A sample of inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorder (AUD) was assessed at baseline (n = 50) and after one year (n = 30). The Habit, Reward, and Fear Scale (HRFS) was employed to quantify affective (fear or reward) and non-affective (habitual) drives for alcohol use, the Alcohol Dependence Scale (ADS) was used to assess clinical outcomes, and the Depression, Anxiety and Stress Scale (DASS-21) was used to quantify and control for associated affective symptoms. RESULTS: There was a significant reduction in the three HRFS scores at the follow-up. Regression analyses demonstrated that greater habit- and fear-related drives at baseline predicted greater decreases in the ADS scores at the endpoint. However, after controlling for age, sex and affective symptoms, only reward and fear were associated with reductions in ADS scores at the end of one year. Prescriptions of naltrexone and antidepressants/benzodiazepines did not predict decreases in reward and fear-related motivations. CONCLUSION: Although we were unable to confirm that habitual subscores at baseline predict worse long-term outcomes among inpatients with AUD, we found that a greater fear and reward motives for the use of alcohol predicted a greater magnitude of improvement in the AUD symptoms after one year. We hope that these findings will help develop new approaches toward AUD treatment and inform models of addiction research.

Latin American Trans-ancestry INitiative for OCD genomics (LATINO): Study Protocol.

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.

When patients with OCD decide to seek, and not to avoid harm: The problem of suicidality in OCD.

Obsessive-compulsive disorder (OCD) is a chronic, distressing, and disabling condition associated with a high risk of suicidal behavior and death by suicide. In this study, the authors describe two cases of OCD patients who developed recurrent suicidal behaviors in response to stressful life events that appeared to "confirm" their obsessive beliefs (termed "confirmatory events"). In both cases, the authors used accepted strategies for treating suicidality in other contexts (such as antidepressants, lithium, and electroconvulsive therapy), which proved unsuccessful. Future studies should investigate personalized strategies to treat suicidality and prevent suicide in OCD patients.