Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Fears of compassion magnify the harmful effects of threat of COVID-19 on mental health and social safeness across 21 countries.

BACKGROUND: The COVID-19 pandemic is a massive global health crisis with damaging consequences to mental health and social relationships. Exploring factors that may heighten or buffer the risk of mental health problems in this context is thus critical. Whilst compassion may be a protective factor, in contrast fears of compassion increase vulnerability to psychosocial distress and may amplify the impact of the pandemic on mental health. This study explores the magnifying effects of fears of compassion on the impact of perceived threat of COVID-19 on depression, anxiety and stress, and social safeness. METHODS: Adult participants from the general population (N = 4057) were recruited across 21 countries worldwide, and completed self-report measures of perceived threat of COVID-19, fears of compassion (for self, from others, for others), depression, anxiety, stress and social safeness. RESULTS: Perceived threat of COVID-19 predicted increased depression, anxiety and stress. The three flows of fears of compassion predicted higher levels of depression, anxiety and stress and lower social safeness. All fears of compassion moderated (heightened) the impact of perceived threat of COVID-19 on psychological distress. Only fears of compassion from others moderated the effects of likelihood of contracting COVID-19 on social safeness. These effects were consistent across all countries. CONCLUSIONS: Fears of compassion have a universal magnifying effect on the damaging impact of the COVID-19 pandemic on mental health and social safeness. Compassion focused interventions and communications could be implemented to reduce resistances to compassion and promote mental wellbeing during and following the pandemic.

Improvements in Compassion and Fears of Compassion throughout the COVID-19 Pandemic: A Multinational Study.

During large-scale disasters, social support, caring behaviours, and compassion are shown to protect against poor mental health outcomes. This multi-national study aimed to assess the fluctuations in compassion over time during the COVID-19 pandemic. Respondents (Time 1 n = 4156, Time 2 n = 980, Time 3 n = 825) from 23 countries completed online self-report questionnaires measuring the flows of compassion (i.e., Compassionate Engagement and Action Scales) and fears of compassion toward self and others and from others (i.e., Fears of Compassion Scales) and mental health at three time-points during a 10-month period. The results for the flows of compassion showed that self-compassion increased at Time 3. Compassion for others increased at Time 2 and 3 for the general population, but in contrast, it decreased in health professionals, possibly linked to burnout. Compassion from others did not change in Time 2, but it did increase significantly in Time 3. For fears of compassion, fears of self-compassion reduced over time, fears of compassion for others showed more variation, reducing for the general public but increasing for health professionals, whilst fears of compassion from others did not change over time. Health professionals, those with compassion training, older adults, and women showed greater flows of compassion and lower fears of compassion compared with the general population, those without compassion training, younger adults, and men. These findings highlight that, in a period of shared suffering, people from multiple countries and nationalities show a cumulative improvement in compassion and reduction in fears of compassion, suggesting that, when there is intense suffering, people become more compassionate to self and others and less afraid of, and resistant to, compassion.

Compassion Protects Mental Health and Social Safeness During the COVID-19 Pandemic Across 21 Countries.

Objectives: The COVID-19 pandemic is having an unprecedented detrimental impact on mental health in people around the world. It is important therefore to explore factors that may buffer or accentuate the risk of mental health problems in this context. Given that compassion has numerous benefits for mental health, emotion regulation, and social relationships, this study examines the buffering effects of different flows of compassion (for self, for others, from others) against the impact of perceived threat of COVID-19 on depression, anxiety, and stress, and social safeness. Methods: The study was conducted in a sample of 4057 adult participants from the general community population, collected across 21 countries from Europe, Middle East, North America, South America, Asia, and Oceania. Participants completed self-report measures of perceived threat of COVID-19, compassion (for self, for others, from others), depression, anxiety, stress, and social safeness. Results: Perceived threat of COVID-19 was associated with higher scores in depression, anxiety, and stress, and lower scores in social safeness. Self-compassion and compassion from others were associated with lower psychological distress and higher social safeness. Compassion for others was associated with lower depressive symptoms. Self-compassion moderated the relationship between perceived threat of COVID-19 on depression, anxiety, and stress, whereas compassion from others moderated the effects of fears of contracting COVID-19 on social safeness. These effects were consistent across all countries. Conclusions: Our findings highlight the universal protective role of compassion, in particular self-compassion and compassion from others, in promoting resilience by buffering against the harmful effects of the COVID-19 pandemic on mental health and social safeness. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-021-01822-2.

The role of social connection on the experience of COVID-19 related post-traumatic growth and stress.

BACKGROUND: Historically social connection has been an important way through which humans have coped with large-scale threatening events. In the context of the COVID-19 pandemic, lockdowns have deprived people of major sources of social support and coping, with others representing threats. Hence, a major stressor during the pandemic has been a sense of social disconnection and loneliness. This study explores how people's experience of compassion and feeling socially safe and connected, in contrast to feeling socially disconnected, lonely and fearful of compassion, effects the impact of perceived threat of COVID-19 on post-traumatic growth and post-traumatic stress. METHODS: Adult participants from the general population (N = 4057) across 21 countries worldwide, completed self-report measures of social connection (compassion for self, from others, for others; social safeness), social disconnection (fears of compassion for self, from others, for others; loneliness), perceived threat of COVID-19, post-traumatic growth and traumatic stress. RESULTS: Perceived threat of COVID-19 predicted increased post-traumatic growth and traumatic stress. Social connection (compassion and social safeness) predicted higher post-traumatic growth and traumatic stress, whereas social disconnection (fears of compassion and loneliness) predicted increased traumatic symptoms only. Social connection heightened the impact of perceived threat of COVID-19 on post-traumatic growth, while social disconnection weakened this impact. Social disconnection magnified the impact of the perceived threat of COVID-19 on traumatic stress. These effects were consistent across all countries. CONCLUSIONS: Social connection is key to how people adapt and cope with the worldwide COVID-19 crisis and may facilitate post-traumatic growth in the context of the threat experienced during the pandemic. In contrast, social disconnection increases vulnerability to develop post-traumatic stress in this threatening context. Public health and Government organizations could implement interventions to foster compassion and feelings of social safeness and reduce experiences of social disconnection, thus promoting growth, resilience and mental wellbeing during and following the pandemic.

Validation of the French version of the Forms of Self-Criticizing/Attacking and Self-Reassuring Scale.

BACKGROUND: Self-criticism and self-reassurance are internal processes of self-to-self relating that have received increasing attention in psychology. The Forms of Self-Criticizing/Attacking and Self-Reassuring Scale (FSCRS), which was first studied by Gilbert, Clarke, Hempel, Miles, and Irons, is a self-report instrument that has been used in various populations and has shown satisfactory reliability. The goal of this work is to explore the psychometric properties of a French version of the scale in a large nonclinical sample. METHOD: Data from 285 nonclinical participants were analysed. RESULTS: Confirmatory factor analysis indicated an acceptable to good fit of the FSCRS items to a three-factor model. Good internal consistency and convergent validity were found. CONCLUSIONS: The French validation results corroborate previous findings in a nonclinical population and confirm that the French version of the FSCRS is a robust and reliable instrument.

Functional deficit in the medial prefrontal cortex during a language comprehension task in patients with schizophrenia.

OBJECTIVE: We and others have observed that patients with schizophrenia commonly presented a reduced left recruitment in language semantic brain regions. However, most studies include patients with leftward and rightward lateralizations for language. We investigated whether a cohort comprised purely of patients with typical lateralization (leftward) presented a reduced left recruitment in semantic regions during a language comprehension task. The goal was to reduce the inter-subject variability and thus improve the resolution for studying functional abnormalities in the language network. METHODS: Twenty-three patients with schizophrenia (DSM-IV) were matched with healthy subjects in age, sex, level of education and handedness. All patients exhibited leftward lateralization for language. Functional MRI was performed as subjects listened to a story comprising characters and social interactions. Functional MRI signal variations were analyzed individually and compared among groups. RESULTS: Although no differences were observed in the recruitment of the semantic language network, patients with schizophrenia presented significantly lower signal variations compared to controls in the medial part of the left superior frontal gyrus (MF1) (x=-6, y=58, z=20; Z(score)=5.6; p<0.001 uncorrected). This region corresponded to the Theory of Mind (ToM) network. Only 5 of the 23 patients (21.7%) and 21 of the 23 (91.3%) control subjects demonstrated a positive signal variation in this area. CONCLUSIONS: A left functional deficit was observed in a core region of the ToM network in patients with schizophrenia and typical lateralizations for language. This functional defect could represent a neural basis for impaired social interaction and communication in patients with schizophrenia.

Semantic hyperpriming in schizophrenic patients: increased facilitation or impaired inhibition in semantic association processing?

Previous studies analyzing semantic priming in schizophrenic patients have reported conflicting results. In the present study, we explored semantic priming in a sample of schizophrenic patients with mild thought disorders. We wondered if distinct cognitive processes, such as facilitation and/or inhibition, underlie semantic hyperpriming and are variously impaired in schizophrenic patients. Using a lexical decision task, we evaluated semantic priming in 15 schizophrenic patients (DSM-IV) with mild thought disorders and 15 healthy controls matched for sex, age, and education level. The task was designed to divide semantic priming into two additive components, namely facilitation effect and inhibition effect. One-sample t-tests were performed to investigate differences in semantic priming, facilitation, and inhibition within each group. ANOVAs were performed to compare the effects of semantic priming, facilitation, and inhibition between groups. Patients displayed greater semantic priming than controls (i.e., hyperpriming), but this was not due to increased facilitation in processing semantically related pairs. On the contrary, hyperpriming was the result of prolonged response time to process semantically unrelated pairs, corresponding to a requirement to inhibit unrelated information. We demonstrated semantic hyperpriming in stabilized schizophrenic patients with mild severity of symptoms. Thus, semantic hyperpriming may be an intrinsic feature of schizophrenia that is not related to the clinical state of patients. Semantic hyperpriming was due to an inhibition effect involved in processing semantically unrelated information not to increased facilitatory effect for related pairs.

Stability of functional language lateralization over time in schizophrenia patients.

BACKGROUND: Cross-sectional functional imaging studies have shown a reduced leftward language lateralization in schizophrenic patients. An unanswered question is whether this reduced leftward lateralization is stable over time or is modified over the course of the illness. METHODS: Ten right-handed (RH) patients (DSM-IV) and 10 RH controls were matched one-to-one for sex, age, and level of education. The subjects underwent two separate fMRI sessions while engaged in a story listening task, 21 months apart. After each session, story comprehension (task performance) was assessed through a 12-item questionnaire. The stability of the decreased asymmetry indices in the semantic region of interest (LANG) was investigated with an ANOVA to compare groups and sessions. In order to test the evolution of functional asymmetry indices at an individual level, a linear correlation between both fMRI session asymmetry indices was calculated in all subjects. Correlations between asymmetry indices and the severity of psychotic symptoms or task performances were computed. RESULTS: The asymmetry indices of the LANG were significantly reduced in patients as compared to controls and strongly correlated between sessions. Values of asymmetry indices were unrelated to either psychotic symptoms or task performances. CONCLUSIONS: This reduced leftward lateralization for language did not vary over time and was not influenced by the psychosis severity or the task performances. This result reinforces the hypothesis that schizophrenia is characterized by a particular organization of language.

Network modeling of resting state connectivity points towards the bottom up theories of schizophrenia.

The dysconnectivity theory of schizophrenia proposes that schizophrenia symptoms arise from abnormalities in neuronal synchrony. Resting-state Functional Connectivity (FC) techniques allow us to highlight synchronization of large-scale networks, the Resting-state Networks (RNs). A large body of work suggests that disruption of RN synchronization could give rise to specific schizophrenia symptoms. The present study aimed to explore within- and between-network FC strength of 34 RNs in 29 patients suffering from schizophrenia, and their relationships with schizophrenia symptoms. Resting-state data were analyzed using independent component analysis and dual-regression techniques. Our results showed that both within-RN and between-RN FC were disrupted in patients with schizophrenia, with a global trend toward weaker FC. This decrease affected more particularly visual, auditory and crossmodal binding networks. These alterations were correlated with negative symptoms, positive symptoms and hallucinations, indicating abnormalities in visual processing and crossmodal binding in schizophrenia. Moreover, we stressed an anomalous synchronization between a visual network and a network thought to be engaged in mental imaging processes, correlated with delusions and hallucinations. Altogether, our results supported the assumption that some schizophrenia symptoms may be related to low-order sensory alterations impacting higher-order cognitive processes, i.e. the "bottom-up" hypothesis of schizophrenia symptoms.

Atypical hemispheric specialization for language in right-handed schizophrenia patients.

BACKGROUND: The literature suggests that schizophrenia could be related to a failure in the setting up of left hemisphere dominance for language. We sought to determine hemispheric specialization for language in schizophrenic patients, using functional magnetic resonance imaging. METHODS: Twenty-one right-handed patients with DSM-IV schizophrenia and 21 right-handed control subjects matched by age, gender, and level of education were recruited. Fractional blood oxygen level dependent (BOLD) signal variations in anatomic regions of interest were compared between groups. Functional asymmetry indices (FAIs) were calculated in a region (LANG) resulting from the merging of activated regions showing a Group x Hemisphere interaction. The FAI difference between each patient and their matched control subject was computed. RESULTS: We found lower BOLD signal changes in patients as compared with their control subjects in a network comprising areas of the left middle temporal gyrus, the left angular gyrus, and the pars triangularis of the left inferior frontal gyrus, merged to constitute LANG. The intra-pair differences of FAIs in this area showed that 76% of the patients exhibited less leftward functional asymmetry than their matched control subjects, including six patients with a rightward asymmetry. CONCLUSIONS: These results demonstrated the existence of an anomaly in left hemisphere specialization for language in schizophrenic subjects.

Impairments of executive/attentional functions in schizophrenia with primary and secondary negative symptoms.

Frontal cognitive inabilities have been amply described in schizophrenic patients with negative symptoms, but findings are controversial. These discrepancies could be due to the fact that negative symptoms are heterogeneous, composed of primary and secondary negative symptoms. The hypothesis tested was that executive/attentional dysfunctions would be significantly more impaired in patients with primary than in patients with secondary negative symptoms independently of IQ, the severity of negative or positive symptoms, treatments and side effects. Fifty-six DSM-IV schizophrenic patients characterized either by primary or secondary negative symptoms and 56 controls matched on age, sex and level of education were assessed with executive/attentional cognitive tests. The categories score of the Modified Card Sorting Test (MCST) and the Verbal Fluency Test, which reflect solving and organizing skills, were significantly more impaired in the primary negative subtype than in the secondary negative subtype. In contrast, scores on the MCST (perseveration), the Trail Making Test and the Stroop Color Word Test, which test the ability to inhibit an automatic response, did not differ between the two subtypes. In conclusion, this study supports the view that primary and secondary negative symptoms could be associated with different levels of executive/attentional dysfunctions.

The subjective quality of life in deficit and nondeficit schizophrenic patients.

We assessed the subjective quality of life (QOL) of 30 deficit schizophrenic patients compared to 112 nondeficit schizophrenic patients. The deficit patients did not differ in term of QOL, total score of positive symptoms, general psychopathology from the nondeficit patients. This result suggested an absence of impact of primary negative symptoms on the subjective QOL in schizophrenic patients.

Functional and structural brain asymmetries in patients with schizophrenia and bipolar disorders.

OBJECTIVES: This study aimed to compare the functional and gray matter asymmetries in patients with schizophrenia (SZ), patients with bipolar disorders (BD), and healthy controls (HCs) to test whether decreased leftward functional hemispheric lateralization and gray matter volume asymmetry could mark the boundary between schizophrenia and bipolar disorder. METHODS: A total of 31 right-handed SZ and 20 right-handed BD underwent a session of functional MRI with a speech listening paradigm. Participants were matched with HCs for gender, age, and education. Functional laterality indices (FLI) and gray matter volume asymmetry indices (GVAI) were computed from the individual functional language network. Correlations between the FLI and GVAI indices were also examined. RESULTS: SZ exhibited significantly decreased leftward functional hemispheric lateralization whereas BD did not. The GVAIs did not differ significantly between SZ and HCs or between BD and HCs. There were positive correlations between GVAIs and FLIs in all groups. CONCLUSIONS: Loss of laterality for language comprehension with retention of gray matter volume asymmetry indicates that gray matter loss alone will not account for the pathophysiology of schizophrenia. Impaired leftward functional hemispheric lateralization for language but not gray matter volume asymmetry can be considered a biomarker of SZ.

Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus, thalamus, and prefrontal cortex.

Single voxel proton magnetic resonance spectroscopy (1H MRS) was used to study the metabolites N-acetylaspartate (NAA), choline (CHO), and myo-inositol (ml) in order to test a neurodegenerative hypothesis in schizophrenia (decrease of NAA, increase of CHO, and increase of ml) and a cerebral asymmetry of these metabolites. 1H MRS was performed in 17 schizophrenia patients and 14 healthy subjects in three cerebral areas highly involved in the pathophysiology of schizophrenia (the prefrontal cortex, the thalamus, and the hippocampus). The ratio amplitudes between metabolites and creatine plus phosphocreatine (Cr) were determined. No difference in the metabolites existed between patients and healthy subjects. However, relationships were noted between NAA/Cr and age in the thalami of the schizophrenia patients (r = -0.37; p = 0.14) and healthy subjects (r = -0.52; p = 0.05). A significant correlation was observed between NAA/Cr and age of onset of illness in the hippocampi of schizophrenia patients (r = -0.59; p < 0.05). Moreover, NAA/Cr was lower in the right than in the left prefrontal cortex in both schizophrenia patients and healthy subjects. There was no relationship between the metabolites and duration of illness or dose of antipsychotics. These findings might suggest a neurodegenerative process in the hippocampi of schizophrenia patients with late onset of illness, and the NAA/Cr ratio could be a marker of aging in the thalami.

Relationship between performance on the Stroop test and N-acetylaspartate in the medial prefrontal cortex in deficit and nondeficit schizophrenia: preliminary results.

The aim of this research was to investigate the relationship between performance on the Stroop test and N-acetylaspartate/creatine assessed using proton magnetic resonance spectroscopy in the medial prefrontal cortex (MPFC) of schizophrenia patients. The Schedule for the Deficit Syndrome was used to subdivide the schizophrenia patients into deficit (n=5) and nondeficit (n=17) subtypes. Twenty-one control subjects served as a comparison group. A strong correlation between right-sided N-acetylaspartate/creatine levels and Stroop scores was found in the deficit patients but not in the nondeficit patients and the controls. This result suggests a relationship between a dysfunction of the right medial prefrontal cortex and a deficit in selective attention in schizophrenia patients with the deficit syndrome.

Sinistrality in subtypes of schizophrenia.

UNLABELLED: Sinistrality, characterized by an excess of non-right-handedness, has been reported in schizophrenic patients, but the findings are controversial. AIM: As sinistrality could be linked to a failure of hemisphere specialization in schizophrenia that would translate into language disorders, sinistrality was found out in disorganized and positive schizophrenic patients characterized by language disorders. METHODS: Seventy-three schizophrenic patients (DSM IV) and 81 controls were evaluated with the Edinburgh Handedness Inventory (EHI). Patients were evaluated and classified into five subtypes (deficit, positive, disorganized, mixed and residual) with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome. RESULTS: Disorganized patients had a significantly more severe sinistrality in comparison to the deficit, residual and mixed subtypes and controls. A negative correlation was found between the disorganization and the EHI scores (r = - 0.34; P < 0.01). A significantly more severe sinistrality was also observed in the positive subtype in comparison to controls, but there was no correlation between hallucinatory and EHI scores (r = 0.06). CONCLUSION: The findings provided further evidence that the defects in the normal process of lateralization observed in schizophrenia affects primarily disorganized patients.

Functional hemispheric lateralization for language in patients with schizophrenia.

BACKGROUND: It is widely reported that patients with schizophrenia exhibit decreased hemispheric lateralization. However, no study has evaluated relationships between the hemispheric anatomical and functional asymmetry in language areas. The present study aimed to determine whether decreased leftward hemispheric lateralization could be related to asymmetry of the grey matter volume in patients with schizophrenia. This investigation was the first to use a functional index of laterality to analyze the global functional network specifically involved in the language task. METHODS: Twenty-seven right-handed patients with schizophrenia and 54 right-handed control subjects underwent a session of a functional magnetic resonance imaging (fMRI) with a speech listening paradigm. Functional laterality indices (FLI) were calculated (Wilke, M. and Lidzba, K., 2007. LI-tool: a new toolbox to assess lateralization in functional MR-data. J Neurosci Methods. 163, 128-136). The indices of asymmetry in the volume of grey matter (GVAIs) were computed from the functional language network. RESULTS: Patients with schizophrenia exhibited significantly decreased leftward hemispheric lateralization. There was a positive correlation between GVAIs and FLIs in healthy subjects, while no such correlation was seen in patients with schizophrenia. DISCUSSION: This study reports for the first time a significant relationship between the anatomical and functional asymmetry in healthy subjects, but not in patients with schizophrenia. While decreased leftward functional lateralization for language was observed in patients with schizophrenia compared to the control group, this functional abnormality was not related to asymmetry in the volume of grey matter.