Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance.

BACKGROUND: Preliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing. METHODS: We assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains. RESULTS: OCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks. CONCLUSIONS: Our results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.

Human ventromedial prefrontal cortex and the positive affective processing of safety signals.

Human functional magnetic resonance imaging (fMRI) studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to the learned discrimination of threat and safety signals, although its precise contribution to these processes remains unclear. One hypothesis is that the vmPFC supports the positive affective processing of safety signals linked to their implicit stress-relieving properties. We set out to test this hypothesis and to examine the specificity of vmPFC responses to safety signal processing versus its high level of 'default mode' activity. Sixty participants completed an fMRI conditioning task that involved the generation of a conditioned threat (CS+) and safety (CS-) signal following the completion of a pre-conditioning baseline. Confirming past findings, activation of the vmPFC and other midline cortical and parietal areas - broadly resembling the default mode network - robustly discriminated between the CS- and CS+. However, when adjusting for this network's characteristic 'baseline' activity, only a subset of regions, including the vmPFC, was activated by the CS-. Regional selectivity for safety signal processing was confirmed by demonstrating a significant correlation between the magnitude of vmPFC responses and self-rated positive affect evoked by the CS-. Taken together, our current findings confirm a link between human vmPFC activity and the positive affective processing of safety signals. We discuss these findings with regards a broader model of human vmPFC function and its suggested higher-order contribution to emotionally adaptive behavior.

Conditioned Subjective Responses to Socially Relevant Stimuli in Social Anxiety Disorder and Subclinical Social Anxiety.

UNLABELLED: Although enhanced fear conditioning has been implicated in the origins of social anxiety disorder (SAD), laboratory evidence in support of this association is limited. Using a paradigm employing socially relevant unconditioned stimuli, we conducted two separate studies to asses fear conditioning in individuals with SAD and non-clinical individuals with high social anxiety (subclinical social anxiety [SSA]). They were compared with age-matched and gender-matched individuals with another anxiety disorder (panic disorder with agoraphobia) and healthy controls (Study 1) and with individuals with low social anxiety (Study 2). Contrary to our expectations, in both studies, self-report measures (ratings of anxiety, unpleasantness and arousal to the conditioned stimuli) of fear conditioning failed to discriminate between SAD or SSA and the other participant groups. Our results suggest that enhanced fear conditioning does not play a major role in pathological social anxiety. KEY PRACTITIONER MESSAGE: We used a social conditioning paradigm to study fear conditioning in clinical and subclinical social anxiety. We found no evidence of enhanced fear conditioning in social anxiety individuals. Enhanced fear conditioning may not be a hallmark of pathological social anxiety.

Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Characterizing human safety learning via Pavlovian conditioned inhibition.

Deficient safety learning has been implicated in the pathogenesis of anxiety disorders. Despite increased translational interest, there has been limited research on the basis of safety learning in humans. Here, we examined safety learning in seventy-three healthy participants via a modified Pavlovian conditioned inhibition paradigm, featuring a conditioned threat stimulus that was reinforced alone (A+), but not when combined with a second stimulus (the conditioned inhibitor, AX-). During a test phase, X and a control safety cue (C) were combined with a second threat stimulus to assess their inhibition of threat responses, measured via skin conductance (SCRs) and US-expectancy ratings. Both stimuli exhibited conditioned inhibition, but X suppressed ratings by a greater magnitude than C. Trait anxiety also predicted increased US-expectancy ratings of X. These findings suggest that a Pavlovian inhibitor accrues greater safety value than a merely unreinforced safety signal. Conditioned inhibition paradigms may have utility in the ongoing study of safety learning and its relevance to anxious psychopathology.

The neurobiology of human fear generalization: meta-analysis and working neural model.

Fear generalization to stimuli resembling a conditioned danger-cue (CS+) is a fundamental dynamic of classical fear-conditioning. Despite the ubiquity of fear generalization in human experience and its known pathogenic contribution to clinical anxiety, neural investigations of human generalization have only recently begun. The present work provides the first meta-analysis of this growing literature to delineate brain substrates of conditioned fear-generalization and formulate a working neural model. Included studies (K = 6, N = 176) reported whole-brain fMRI results and applied generalization-gradient methodology to identify brain activations that gradually strengthen (positive generalization) or weaken (negative generalization) as presented stimuli increase in CS+ resemblance. Positive generalization was instantiated in cingulo-opercular, frontoparietal, striatal-thalamic, and midbrain regions (locus coeruleus, periaqueductal grey, ventral tegmental area), while negative generalization was implemented in default-mode network nodes (ventromedial prefrontal cortex, hippocampus, middle temporal gyrus, angular gyrus) and amygdala. Findings are integrated within an updated neural account of generalization centering on the hippocampus, its modulation by locus coeruleus and basolateral amygdala, and the excitation of threat- or safety-related loci by the hippocampus.

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate.

OBJECTIVE: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( n = 52) during the first wave of the pandemic (weeks 10-16 of 2020). METHODS: We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces. RESULTS: We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03% in < 50-year-old, 0.22% in 50-59-year-old, 0.9% in 60-69-year-old, 3.3% in 70-79-year-old, 12.6% in 80-89-year-old, and 26.5% in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population. CONCLUSION: The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.

Study Protocol-Coping With the Pandemics: What Works Best to Reduce Anxiety and Depressive Symptoms.

Background: The coronavirus disease 2019 (COVID-19) pandemic and lockdown might increase anxiety and depressive symptoms in most individuals. Health bodies recommend several coping behaviors to protect against such symptoms, but evidence on the relationship between these behaviors and symptoms mostly comes from cross-sectional studies in convenience samples. We will conduct a prospective longitudinal study of the associations between coping behaviors and subsequent anxiety and depressive symptoms during the COVID-19 pandemic in a representative sample of the Spanish general adult population. Methods: We will recruit 1,000 adult participants from all autonomous communities of Spain and with sex, age, and urbanicity distributions similar to those of their populations and assess anxiety and depressive symptoms and coping behaviors using fortnightly questionnaires and real-time methods (ecological momentary assessments) for 1 year. The fortnightly questionnaires will inquire about anxiety and depressive symptoms [General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9)] and the frequency of 10 potential coping behaviors (e.g., follow a routine) during the past 2 weeks. In addition, we will collect several variables that could confound or moderate these associations. These will include subjective well-being [International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) and Satisfaction with Life Scale (SWLS)], obsessive-compulsive symptoms [Obsessive Compulsive Inventory-Revised (OCI-R)], personality and emotional intelligence [International Personality Item Pool (IPIP) and Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF)], sociodemographic factors (e.g., work status, housing-built environment), and COVID-19 pandemic-related variables (e.g., hospitalizations or limitations in social gatherings). Finally, to analyze the primary relationship between coping behaviors and subsequent anxiety and depressive symptoms, we will use autoregressive moving average (ARMA) models. Discussion: Based on the study results, we will develop evidence-based, clear, and specific recommendations on coping behaviors during the COVID-19 pandemic and lockdown. Such suggestions might eventually help health bodies or individuals to manage current or future pandemics.

PRimary carE digital Support ToOl in mental health (PRESTO): Design, development and study protocols.

BACKGROUND: About 30-50% of Primary Care (PC) users in Spain suffer mental health problems, mostly mild to moderate anxious and depressive symptoms, which account for 2% of Spain's total Gross domestic product and 50% of the costs associated to all mental disorders. Mobile health tools have demonstrated to cost-effectively reduce anxious and depressive symptoms while machine learning (ML) techniques have shown to accurately detect severe cases. The main aim of this project is to develop a comprehensive ML digital support platform (PRESTO) to cost-effectively screen, assess, triage, and provide personalized treatments for anxious and depressive symptoms in PC. METHODS: The project will be carried out in 3 complementary phases: First, a ML predictive severity model will be built based on all the cases referred to the PC mental health support programme during the last 5 years in Catalonia. Simultaneously, a smartphone app to monitor and deliver psychological interventions for anxiety and depressive symptoms will be developed and tested in a clinical trial. Finally, the ML models and the app will be integrated in a comprehensive decision-support platform (PRESTO) which will triage and assign to each patient a specific intervention based on individual personal and clinical characteristics. The effectiveness of PRESTO to reduce waiting times in receiving mental healthcare will be tested in a stepped-wedge cluster randomized controlled trial in 5 PC centres. DISCUSSION: PRESTO will offer timely and personalized cost-effective mental health treatment to people with mild to moderate anxious and depressive symptoms. This will result in a reduction of the burden of mental health problems in PC and on society as a whole. TRIAL REGISTRATION: The project and their clinical trials were registered in Clinical Trials.gov: NCT04559360 (September 2020).

The Symptom Checklist-Revised (SCL-90-R) is able to discriminate between simulation and fibromyalgia.

This study assessed the ability of the Symptom Checklist-Revised (SCL-90-R) to discriminate between two groups of fibromyalgia patients (those who were about to begin a treatment including the explicit aim of returning to work and those who were initiating a legal procedure to obtain permanent disability compensation) and two groups of healthy volunteers (medical students and psychology graduates), who were asked to produce a symptomatic resemblance to a chronic pain disorder. Logistic regression analyses were applied to the SCL-90-R subscales and individual probabilistic indices of simulation were calculated. Results showed that the SCL-90-R was able to discriminate between healthy subjects and both groups of patients with a high sensitivity and specificity. The individual indices of simulation, which might be more useful in clinical practice than the comparison of the SCL-90-R profiles, also showed an appropriate level of accuracy.

Impact of mental disorders and chronic physical conditions in health-related quality of life among primary care patients: results from an epidemiological study.

PURPOSE: To estimate the comorbidity of mental disorders with chronic physical conditions and to assess their independent and combined effects on health-related quality of life (HRQOL). METHODS: Face-to-face cross-sectional survey of adult attendants to public primary care (PC) centres from Catalonia (Spain). A total of 3,815 out of 5,402 selected patients provided data for this study. We report frequency of chronic physical conditions among participants with mental disorders and the contribution of each mental disorder and chronic physical condition to HRQOL. RESULTS: Chronic pain is the most frequent condition among those with mental disorders (74.54%). The effect of chronic physical conditions on HRQOL is rather minor when compared to the effect of mental disorders (especially mood disorders). However, chronic pain plays an important role in HRQOL loss. CONCLUSIONS: Mood disorders and chronic pain negatively affect HRQOL of PC patients. Especial efforts should be made to detect and treat mental disorders and chronic pain at this level.

Meta-analysis of Voxel-Based Neuroimaging Studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI).

Most methods for conducting meta-analysis of voxel-based neuroimaging studies do not assess whether effects are not null, but whether there is a convergence of peaks of statistical significance, and reduce the assessment of the evidence to a binary classification exclusively based on p-values (i.e., voxels can only be "statistically significant" or "non-statistically significant"). Here, we detail how to conduct a meta-analysis using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), a novel method that uses a standard permutation test to assess whether effects are not null. We also show how to grade the strength of the evidence according to a set of criteria that considers a range of statistical significance levels (from more liberal to more conservative), the amount of data or the detection of potential biases (e.g., small-study effect and excess of significance). To exemplify the procedure, we detail the conduction of a meta-analysis of voxel-based morphometry studies in obsessive-compulsive disorder, and we provide all the data already extracted from the manuscripts to allow the reader to replicate the meta-analysis easily. SDM-PSI can also be used for meta-analyses of functional magnetic resonance imaging, diffusion tensor imaging, position emission tomography and surface-based morphometry studies.

Treatment adequacy of anxiety and depressive disorders: primary versus specialised care in Spain.

BACKGROUND: Literature suggests that a high proportion of the population with mental disorders remains either untreated or poorly treated. This study aimed to describe the adequacy of treatment for Anxiety and Depressive disorders in Spain, how this differs between providers (primary versus specialised care) and which factors are associated with appropriate care. METHOD: Data were derived from the Spanish sample (N=5473) of the European Study of the Epidemiology of Mental Disorders (ESEMeD), a cross sectional study in a representative sample of adults. The subsample analyzed was composed by the 133 subjects with a mental disorder in the year prior to the interview who received treatment. Treatment adequacy was evaluated in two different ways: (1) considering definitions of minimally adequate treatment evidence based guidelines and criteria used in other epidemiological studies; (2) considering experts rating of treatment appropriateness based on the information contained in the case vignettes created from the CIDI answers. Generalised Estimating Equation (GEE) models and simple logistic regression were conducted to assess the correlates of adequate treatment. RESULTS: Similar proportions of patients in specialty and general medical treatment received a minimally adequate treatment (31.8% and 30.5%, respectively). Associated factors to appropriateness were living in a large city, having a high educational level, and having a good self rated health state. LIMITATIONS: Treatment adequacy was based on simple information and criteria. CONCLUSIONS: Only one third of the mental health treatment in Spain met minimal adequacy criteria. More research is needed in order to find out reasons for these low rates.

Influence of individual differences in Behavioral Inhibition System on the magnitude and time course of the fear-potentiated startle.

Previous research has shown that the startle reflex is potentiated during experimentally induced anxiety (fear-potentiated startle). In the present study, the magnitude and time course of the startle blink reflex were examined among 35 undergraduates scoring one standard deviation above (n = 14) or below (n = 21) the mean in a self-report measure of sensitivity to punishment (SP) in a paradigm involving the anticipation of electric shocks. Contrary to our predictions, SP did not relate to differences in the magnitude or in the time course of fear-potentiated startle. Our data do not support an association between this individual differences variable and the fear-potentiated startle.

Looking at the heart of low and high heart rate variability fearful flyers: self-reported anxiety when confronting feared stimuli.

Previous research has shown that phobic subjects with low heart rate variability (HRV) are less able to inhibit an inappropriate response when confronted with threatening words compared to phobic subjects with high HRV [Johnsen, B.H., Thayer, J.F., Laberg, J.C., Wormnes, B., Raadal, M., Skaret, E., et al., 2003. Attentional and physiological characteristics of patients with dental anxiety. Journal of Anxiety Disorders, 17, 75-87]. The aim of this study was to evaluate changes in self-reported anxiety when low HRV and high HRV fearful flyers (N=15) and a matched control group (N=15) were exposed to flight-related pictures, flight-related sounds or both pictures and sounds. We hypothesized that sounds would be crucial to evoke fear. Also, low HRV fearful flyers were expected to report higher anxiety than high HRV fearful flyers assuming anxiety as their inappropriate response. Decreases on HRV measures were also predicted for a subgroup of phobic participants (N=10) when confronted with the feared stimuli. Our data supported the hypothesis that sounds are crucial in this kind of phobia. Low HRV fearful flyers reported higher anxiety than high HRV fearful flyers in two out of three aversive conditions. The predicted HRV decreases were not found in this study. Results are discussed in the context of avoidance of exposure-based treatments.

Conditioned Fear Acquisition and Generalization in Generalized Anxiety Disorder.

Abnormal fear conditioning processes (including fear acquisition and conditioned fear-generalization) have been implicated in the pathogenesis of anxiety disorders. Previous research has shown that individuals with panic disorder present enhanced conditioned fear-generalization in comparison to healthy controls. Enhanced conditioned fear-generalization could also characterize generalized anxiety disorder (GAD), but research so far is inconclusive. An important confounding factor in previous research is comorbidity. The present study examined conditioned fear-acquisition and fear-generalization in 28 patients with GAD and 30 healthy controls using a recently developed fear acquisition and generalization paradigm assessing fear-potentiated startle and online expectancies of the unconditioned stimulus. Analyses focused on GAD patients without comorbidity but included also patients with comorbid anxiety disorders. Patients and controls did not differ as regards fear acquisition. However, contrary to our hypothesis, both groups did not differ either in most indexes of conditioned fear-generalization. Moreover, dimensional measures of GAD symptoms were not correlated with conditioned fear-generalization indexes. Comorbidity did not have a significant impact on the results. Our data suggest that conditioned fear-generalization is not enhanced in GAD. Results are discussed with special attention to the possible effects of comorbidity on fear learning abnormalities.

High sensitivity to punishment and low impulsivity in obsessive-compulsive patients with hoarding symptoms.

Recent factor-analytic studies involving over 2000 patients have reduced the symptoms of obsessive-compulsive disorder (OCD) into a few dimensions or potentially overlapping syndromes. Hoarding consistently emerged as a separate factor in all these studies. This study investigated the relationship between OCD symptom dimensions and normal personality traits in a sample of 56 OCD patients. They were administered the Sensitivity to Punishment and Sensitivity to Reward Questionnaire and the Eysenck Personality Questionnaire, derived from Gray's and Eysenck's personality models, respectively. The personality scores were correlated with previously identified symptom dimensions from the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (Y-BOCS-SC), controlling for overall illness severity. High scores on the hoarding dimension of the Y-BOCS-SC were positively correlated with scores on the Sensitivity to Punishment scale and negatively with Eysenck's Psychoticism scale. While high sensitivity to punishment is a personality feature common to many OCD patients, it is more strongly pronounced in patients with hoarding symptoms. These patients also appear to be less impulsive or novelty seeking as reflected by low scores on Eysenck's Psychoticism scale. High sensitivity to punishment and low novelty seeking in OCD hoarders might explain their poor compliance and response to conventional treatments, but this question needs to be explored further in a prospective treatment study.

Personality characteristics in obsessive-compulsive disorder and individuals with subclinical obsessive-compulsive problems.

OBJECTIVE: To assess the relationship between normal personality traits and obsessive-compulsive (OC) phenomena in individuals with subclinical OC problems and patients whose problems met diagnostic criteria for obsessive-compulsive disorder (OCD). METHOD: In Study 1, 25 healthy volunteers with high scores on the Padua Inventory (PI) and 28 controls with low scores on the PI were compared on the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the Eysenck Personality Questionnaire (EPQ), and measures of depression and state anxiety. In Study 2, 56 treatment-seeking participants meeting DSM-IV criteria for OCD and 40 healthy volunteers of similar sociodemographic characteristics were compared on the same measures. RESULTS: Both individuals with subclinical OC problems and OCD patients scored significantly higher than their respective control groups on sensitivity to punishment, neuroticism and psychoticism. OCD patients, but not individuals with subclinical OC problems, scored lower in extraversion than their respective controls. Neuroticism was the strongest predictor of high scores on the PI in Study 1, while psychoticism was the strongest predictor of the presence of an OCD diagnosis in Study 2. CONCLUSION: Healthy participants with high scores on OC measures and OCD patients share various personality traits but can also be distinguished according to the level of extraversion, neuroticism and psychoticism.