White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Stress, anxiety, and depression trajectories during the "first wave" of the COVID-19 pandemic: what drives resilient, adaptive and maladaptive responses in the Portuguese population?

Introduction: The COVID-19 outbreak and the community mitigation strategies implemented to reduce new SARS-CoV-2 infections can be regarded as powerful stressors with negative consequences on people's mental health. Although it has been shown that negative emotional symptoms subside during lockdown, it is likely the existence of inter-individual differences in stress, anxiety and depression trajectories throughout lockdown. Objectives: We aimed to cluster participants' according to their trajectories of stress, anxiety and depression scores throughout lockdown, and identify the sociodemographic, clinical, and lifestyle factors that may distinguish the subjects included in the different clusters. Methods: From March 23, 2020, to May 31, 2020, participants completed weekly online questionnaires on sociodemographic information (age, sex, education level, and employment status), psychological functioning (DASS-21, NEO-FFI-20), and clinical data (psychiatric disorders, psychiatric medication, physical disorders). Data regarding smoking status, alcohol consumption, physical activity, and time spent daily looking for COVID-19-related information were also collected. Stress, anxiety and depression trajectories were determined using latent class mixed models. Results: A total of 2040 participants answered the survey at baseline and 603 participants answered all surveys. Three groups ("Resilient," "Recovered," and "Maladaptive") with distinct mental health trajectories were identified. Younger participants, women, participants with lower education level, not working, studying, diagnosed with a mental disorder, taking psychiatric medication, smokers, those who spent more time consuming COVID-19-related information and those with higher neuroticism tended to cluster in the "Maladaptive" group, placing them at higher risk of persistent negative emotional symptoms during compulsory confinement. Conclusion: Accordingly, a tailored approach to emotional suffering for vulnerable subjects during the COVID-19 and future pandemics must be devised.

How Long Does Adaption Last for? An Update on the Psychological Impact of the Confinement in Portugal.

During the first COVID-19 related confinement in Portugal, there was a decrease in the levels of psychological symptoms measured by the Depression, Anxiety and Stress Scale 21 (March to April 2020). Upon experiencing a new period of restraints in 2021, the psychological impact of this sample was assessed again (N = 322, two more time points). It was expected that the psychological symptoms evidenced in February 2021 would be at similar levels to those found in April 2020, leading to a transfer of adaptation. Contrary to our hypothesis, in the second confinement in Portugal there were higher levels of depression and stress symptoms than at the beginning of the pandemic. On the other hand, the maximum level of anxiety was observed in March 2020. It seems that our perception of the threats in 2021 was not the same as at the onset of COVID-19, or that knowledge was not disseminated to the general population to increase their mental health literacy and help them cope with the imposed challenges.

Altered frontoparietal connectivity in patients with obsessive-compulsive disorder during an fMRI cognitive reappraisal task.

Patients with obsessive-compulsive disorder (OCD) present increased brain activity in orbitofrontal and limbic regions when experiencing negative emotions, which could be related to deficits in emotion regulation abilities. 30 OCD patients and 29 healthy controls (HC) performed a cognitive reappraisal functional magnetic resonance imaging (fMRI) task and completed emotion regulation and OCD symptomatology questionnaires. Besides task activation, connectivity was also compared between groups through psychophysiological interaction analysis (PPI), using regions previously reported to be hyperactive in OCD as seeds. Finally, brain-behavior correlations were performed between activation/connectivity strength in group differential regions and the questionnaires' scores, as well as the emotional ratings reported during the task. Behaviorally, patients with OCD were less successful than controls at lowering the emotional impact of negative images. At the brain level, there were no significant between-group differences in brain activation. Contrarily, PPI analyses showed that HC had increased frontoparietal connectivity when experiencing negative emotions in comparison to OCD patients, while this pattern was reversed when regulating emotions (increased connectivity in patients). Finally, frontoparietal connectivity was correlated with measures of emotion regulation success and OCD symptomatology. Our findings point towards frontoparietal altered connectivity as a potential compensatory mechanism during emotion regulation in OCD patients.

A functional magnetic resonance imaging study of frontal networks in obsessive-compulsive disorder during cognitive reappraisal.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) present difficulties in the cognitive regulation of emotions, possibly because of inefficient recruitment of distributed patterns of frontal cortex regions. The aim of the present study is to characterize the brain networks, and their dysfunctions, related to emotion regulation alterations observed during cognitive reappraisal in OCD. METHODS: Adult patients with OCD (n = 31) and healthy controls (HC; n = 30) were compared during performance of a functional magnetic resonance imaging cognitive reappraisal protocol. We used a free independent component analysis approach to analyze network-level alterations during emotional experience and regulation. Correlations with behavioral scores were also explored. RESULTS: Analyses were focused on six networks encompassing the frontal cortex. OCD patients showed decreased activation of the frontotemporal network in comparison with HC (F(1,58) = 7.81, p = 0.007) during cognitive reappraisal. A similar trend was observed in the left frontoparietal network. CONCLUSIONS: The present study demonstrates that patients with OCD show decreased activation of specific networks implicating the frontal cortex during cognitive reappraisal. These outcomes should help to better characterize the psychological processes modulating fear, anxiety, and other core symptoms of patients with OCD, as well as the associated neurobiological alterations, from a system-level perspective.

Sociodemographic and lifestyle predictors of mental health adaptability during COVID-19 compulsory confinement: A longitudinal study in the Portuguese population.

BACKGROUND: The outbreak of COVID-19 and the physical isolation measures taken by the governments to reduce its propagation might have negative psychological consequences on the population. In this study, we aimed to explore, for the first time, how mental health status fluctuated along the weeks of the emergency state in Portugal, and to identify which factors may shape these changes in mental health outcomes. METHODS: To this end, we conducted an online survey to evaluate demographic, lifestyle and mental health variables (DASS-21 and quality of life) in the Portuguese population at three different time-points. 748 participants (mean age = 39.52, % females = 79.95) provided data at all time-points. RESULTS: We observed that depression, anxiety and stress symptoms seemed to improve as the weeks passed during the state of emergency, while the perception of quality of life and sleep got worse. In particular, being female, younger, actively working, and extroverted appear to be protective factors of mental health adaptability during this particular period. On the contrary, having a psychiatric diagnosis or physical illness, and higher neuroticism seem to be risk factors for mental health worsening. LIMITATIONS: The lack of a more diverse sample could limit the generalizability of our results, and other factors that were not considered in our analysis might also have a significant impact on mental health. CONCLUSIONS: Our results provide relevant and novel insights about the course of mental health changes and its predictors during the outbreak of COVID-19, which may help identify potential vulnerability groups.

Protective Elements of Mental Health Status during the COVID-19 Outbreak in the Portuguese Population.

The outbreak of COVID-19 might produce dramatic psychological effects on individuals' lives. In this study, we aimed to explore the elements that may reduce the negative effects on mental health of the quarantine period imposed by most governments during this worldwide crisis. We conducted an online survey to evaluate demographic, lifestyle and mental health variables in a sample of 1280 Portuguese individuals (79.8% females) with an average age of 37 years. We observed that factors related to living conditions, maintaining work either online or in the workplace, frequency of exercise and absence of previous psychological or physic disorders are protective features of psychological well-being (anxiety, depression, stress and obsessive-compulsive symptoms). Finally, the individuals previously receiving psychotherapeutic support exhibited better psychological indicators if they did not interrupt the process as a consequence of the outbreak. Our results indicate that the practice of physical exercise, reduced consumption of COVID-19 information and the implementation of remote mental healthcare measures might prevent larger impacts on mental health during the COVID-19 outbreak.

Stress Influences the Effect of Obsessive-Compulsive Symptoms on Emotion Regulation.

Obsessive-compulsive disorder (OCD) is associated with emotion regulation impairments, namely the frequent use of maladaptive strategies such as suppression and the decreased use of reappraisal strategies. Additionally, these patients exhibit elevated stress levels. Since stress exposure affects emotion regulation abilities, stress might influence the relationship between obsessive-compulsive symptoms and emotion regulation. In this study, we explored the effects of stress and obsessive-compulsive symptoms on emotion regulation in a sample of healthy and OCD individuals. We used self-reported psychometric scales to measure stress levels, obsessive-compulsive symptoms, and emotion reappraisal and suppression skills. We applied multiple regression and mediation analyses. Our results demonstrated that increased reappraisal scores were associated with higher suppression scores. Additionally, elevated stress values predicted increased scores for suppression and decreased scores for reappraisal. Furthermore, the reappraisal abilities resulted from a combination of a direct effect of obsessive-compulsive symptoms and an indirect effect of obsessive-compulsive symptoms mediated by stress. The reliance on suppression strategies and the difficulty in using reappraisal approaches are explained by stress levels and are not directly explained by obsessive-compulsive symptoms. This study highlights the necessity of targeting stress in current therapy-based treatments for OCD.