High unrecognized SARS-CoV-2 exposure of newly admitted and hospitalized psychiatric patients.

BACKGROUND: Patients with pre-existing mental disorders are at higher risk for SARS-CoV-2 infection and adverse outcomes, and severe mental illness, including mood and psychosis spectrum disorders, is associated with increased mortality risk. Despite their increased risk profile, patients with severe mental illness have been understudied during the pandemic, with limited estimates of exposure in inpatient settings. OBJECTIVE: The aim of this study was to describe the SARS-CoV-2 seroprevalence and antibody titers, and pro-inflammatory cytokine concentrations of newly admitted or hospitalized psychiatric inpatients without known history of COVID-19 infection, using robust quantitative multi-antigen assessments, and compare patients' exposure to that of hospital staff. METHODS: This multi-centric, cross-sectional study compared SARS-CoV-2 seroprevalence and titers of 285 patients (University Psychiatric Centre Duffel [UPCD] N = 194; Assistance-Publique-Hopitaux de Paris [AP-HP] N = 91), and 192 hospital caregivers (UPCD N = 130; AP-HP N = 62) at two large psychiatric care facilities between January 1st and the May 30th 2021. Serum levels of SARS-CoV-2 antibodies against Spike proteins (full length), spike subunit 1 (S1), spike subunit 2 (S2), spike subunit 1 receptor binding domain (S1-RBD) and Nucleocapsid proteins were quantitatively determined using an advanced capillary Western Blot technique. To assess the robustness of the between-group seroprevalence differences, we performed sensitivity analyses with stringent cut-offs for seropositivity. We also assessed peripheral concentrations of IL-6, IL-8 and TNF-a using ELLA assays. Secondary analyses included comparisons of SARS-CoV-2 seroprevalence and titers between patient diagnostic subgroups, and between newly admitted (hospitalization ≤ 7 days) and hospitalized patients (hospitalization > 7 days) and correlations between serological and cytokines. RESULTS: Patients had a significantly higher SARS-CoV-2 seroprevalence (67.85 % [95% CI 62.20-73.02]) than hospital caregivers (27.08% [95% CI 21.29-33.77]), and had significantly higher global SARS-CoV-2 titers (F = 29.40, df = 2, p < 0.0001). Moreover, patients had a 2.51-fold (95% CI 1.95-3.20) higher SARS-CoV-2 exposure risk compared to hospital caregivers (Fisher's exact test, P < 0.0001). No difference was found in SARS-CoV-2 seroprevalence and titers between patient subgroups. Patients could be differentiated most accurately from hospital caregivers by their higher Spike protein titers (OR 136.54 [95% CI 43.08-481.98], P < 0.0001), lower S1 (OR 0.06 [95% CI 0.02-0.15], P < 0.0001) titers and higher IL-6 (OR 3.41 [95% CI 1.73-7.24], P < 0.0001) and TNF-α (OR 34.29 [95% CI 5.00-258.87], P < 0.0001) and lower titers of IL-8 (OR 0.13 [95% CI 0.05-0.30], P < 0.0001). Seropositive patients had significantly higher SARS-COV-2 antibody titers compared to seropositive hospital caregivers (F = 19.53, df = 2, P < 0.0001), while titers were not different in seronegative individuals. Pro-inflammatory cytokine concentrations were not associated with serological status. CONCLUSION: Our work demonstrated a very high unrecognized exposure to SARS-CoV-2 among newly admitted and hospitalized psychiatric inpatients, which is cause for concern in the context of highly robust evidence of adverse outcomes following COVID-19 in psychiatric patients. Attention should be directed toward monitoring and mitigating exposure to infectious agents within psychiatric hospitals.

The relationship between immune and cognitive dysfunction in mood and psychotic disorder: a systematic review and a meta-analysis.

BACKGROUND: In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of inflammatory cytokines, kynurenine metabolites, and markers of microglial activation. The current meta-analysis synthesizes all available clinical evidence on the associations between immunomarkers (IMs) and cognition in these psychiatric illnesses. METHODS: Pubmed, Web of Science, and Psycinfo were searched for peer-reviewed studies on schizophrenia spectrum disorder (SZ), bipolar disorder (BD), or major depressive disorder (MDD) including an association analysis between at least one baseline neuropsychological outcome measure (NP) and one IM (PROSPERO ID:CRD42021278371). Quality assessment was performed using BIOCROSS. Correlation meta-analyses, and random effect models, were conducted in Comprehensive Meta-Analysis version 3 investigating the association between eight cognitive domains and pro-inflammatory and anti-inflammatory indices (PII and AII) as well as individual IM. RESULTS: Seventy-five studies (n = 29,104) revealed global cognitive performance (GCP) to be very weakly associated to PII (r = -0.076; p = 0.003; I2 = 77.4) or AII (r = 0.067; p = 0.334; I2 = 38.0) in the combined patient sample. Very weak associations between blood-based immune markers and global or domain-specific GCP were found, either combined or stratified by diagnostic subgroup (GCP x PII: SZ: r = -0.036, p = 0.370, I2 = 70.4; BD: r = -0.095, p = 0.013, I2 = 44.0; MDD: r = -0.133, p = 0.040, I2 = 83.5). We found evidence of publication bias. DISCUSSION: There is evidence of only a weak association between blood-based immune markers and cognition in mood and psychotic disorders. Significant publication and reporting biases were observed and most likely underlie the inflation of such associations in individual studies.

A Survey on BDSM-related Activities: BDSM Experience Correlates with Age of First Exposure, Interest Profile, and Role Identity.

BDSM is an omnibus term covering a spectrum of activities within bondage/discipline, dominance/submission, and sadism/masochism relationships. To date, BDSM practitioners experience stigma due to a general unfamiliarity with the practice and marginalization of this type of sexual behavior. Destigmatization occurs partly through knowledge expansion and identification with the stigmatized group. In this study within the Belgian population, we aimed to characterize certain aspects of socioeconomic status and specific BDSM preferences of individuals with differing BDSM experience levels. We show that individuals who perform BDSM in a community setting (BDSM clubs, events. BDSM-CP) are generally higher educated, are significantly younger when first becoming aware of their inclination toward kink-oriented sex, and have a more strict BDSM role identity (Dom vs. Sub) than individuals who engage in BDSM-related activities in a private setting (BDSM-PP). This latter group in turn display a more pronounced Dom/Sub identification than individuals who only fantasize about the practice (BDSM-F). Our data indicate BDSM interest is a sexual preference already manifesting at early age, with role identification profiles becoming gradually more pronounced based on the practitioner's contextual experience.

Psychomotor assessment as a tool to differentiate schizophrenia from other psychotic disorders.

GOAL: The aim of this study is to assess to what extent psychomotor assessment can aid the clinician in differentiating between schizophrenia and other psychotic disorders. METHODS: Enrolled subjects were recent in remission patients (n=304), who all met DSM-IV (APA, 2013) criteria for either schizophrenia (Sz; n=117), schizoaffective disorder (SaD; n=36), psychotic disorder not otherwise specified (P-NOS) (n=86), substance/medication-induced psychotic disorder (SIPD; n=33) or major depressive disorder with psychotic features (MDD-p; n=32). The patients were submitted to a psychomotor test battery. RESULTS: Patients with schizophrenia generally perform worse on most tests. Using cluster analysis a combination of three tests, namely the sensory integration subscale of the Neurological Evaluation Scale (NES), a Figure Copying Task (FCT) and the finger tapping test (FTT), came out to be useful to clinically differentiate between schizophrenia and substance-induced psychotic disorder (SIPD) or psychosis not otherwise specified (P-NOS). When comparing schizophrenia only to a group of patients with SIPD, the differentiation potential becomes even greater with a 76.1% chance to correctly diagnose patients with schizophrenia and 75% chance for patients with SIPD. CONCLUSION: A combination of NES, FCT and FTT shows promising results as a clinical tool in daily practice to differentiate schizophrenia from other psychotic disorders. Future prospective studies to confirm these results are necessary.

[The effect of mood-stabilising drugs on cytokine levels in bipolar disorder: a systematic review]. / De impact van stemmingsstabiliserende geneesmiddelen op cytokineconcen-traties bij patiënten met een bipolaire stoornis: een systematisch literatuur-onderzoek1.

ACHTERGROND: Veranderde cytokineconcentraties bij personen met een bipolaire stoornis ten opzichte van controle-personen suggereren een rol van het immuunsysteem in de pathofysiologie van bipolaire stoornis. Farmacotherapie is een belangrijke verstorende factor in klinisch onderzoek naar cytokineconcentraties.
DOEL: Evalueren van cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis en van het effect van stemmingsstabiliserende geneesmiddelen op deze concentraties.
METHODE: We doorzochten systematisch PubMed en Embase naar klinische studies die cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis beschrijven of het effect van een individueel stemmingsstabiliserend geneesmiddel op deze concentraties evalueren.
RESULTATEN: Van de 564 gescreende artikelen werden er 17 geïncludeerd. Resultaten bij medicatievrije patiënten toonden stemmingsgerelateerde cytokineveranderingen. Hoewel geen data over de kortetermijneffecten van lithium beschikbaar waren, was lithiumgebruik langer dan 2 maanden geassocieerd met normale cytokineconcentraties. Twee studies rapporteerden geen effect van valproïnezuur. We vonden geen studies over carbamazepine, lamotrigine of antipsychotica.
CONCLUSIE: Dit systematisch literatuuroverzicht toont stemmingsgerelateerde cytokineveranderingen bij medicatievrije patiënten met een bipolaire stoornis met de meeste evidentie voor een pro-inflammatoire immuunrespons tijdens manie. Euthymie en langdurig lithiumgebruik zijn geassocieerd met normale cytokineconcentraties. Er is een belangrijke methodologische heterogeniteit en onvoldoende replicatie tussen studies. Longitudinale studies met medicatievrije beginmetingen, gerandomiseerde monotherapeutische behandelprotocollen en nauwkeurige monitoring van stemming zijn noodzakelijk.
BACKGROUND: Alterations of the cytokine level in persons with bipolar disorder - when compared to controls - suggest that the immune system plays a role in the pathophysiology of bipolar disorder. Pharmacotherapy is an important confounding factor in clinical research on cytokine levels.
AIM: To evaluate the evidence on cytokine levels in medication-free bipolar disorder and to study the effects that single mood-stabilising drugs have on these levels.
METHOD: We searched PubMed and Embase systematically in order to single out clinical studies that reported on cytokine levels in medication-free bipolar disorder or that commented on the effects of single mood-stabilising drugs on cytokine levels.
RESULTS: Of the 564 articles that we screened, we detected 17 that were particularly relevant for our investigation. Results for medication-free patients point to mood-related alterations in cytokine levels. Although we found no data relating to short-term effects of lithium, the use of lithium in euthymic populations was associated with normal cytokine levels. Two studies reported no effect of valproate. We did not find any studies relating to carbamazepine, lamotrigine or antipsychotics.
CONCLUSION: Our systematic review of the literature suggests the presence of mood-related changes in cytokine levels in medication-free patients with bipolar disorder, with the most evidence for a proinflammatory response during a manic episode. Euthymia and long-term use of lithium use are associated with normal cytokine levels. There is considerable heterogeneity in the methods used in these studies and too little replication. Future research will have to include longitudinal studies with medication-free baseline measurements. It will also be necessary to draw up single-drug treatment protocols and to conduct intensive mood-related monitoring.

Accessory cells for ß-cell transplantation.

Despite recent advances, insulin therapy remains a treatment, not a cure, for diabetes mellitus with persistent risk of glycaemic alterations and life-threatening complications. Restoration of the endogenous ß-cell mass through regeneration or transplantation offers an attractive alternative. Unfortunately, signals that drive ß-cell regeneration remain enigmatic and ß-cell replacement therapy still faces major hurdles that prevent its widespread application. Co-transplantation of accessory non-islet cells with islet cells has been shown to improve the outcome of experimental islet transplantation. This review will highlight current travails in ß-cell therapy and focuses on the potential benefits of accessory cells for islet transplantation in diabetes.

Neurogenin 3+ cells contribute to ß-cell neogenesis and proliferation in injured adult mouse pancreas.

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to ß cells ex vivo. Here we evaluate the role of Ngn3(+) cells in ß cell expansion in situ. PDL not only induced doubling of the ß cell volume but also increased the total number of islets. ß cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the ß cell expansion was attributable to proliferation of pre-existing ß cells. At sufficiently high Ngn3 expression level, upto 14% of all ß cells and 40% of small islet ß cells derived from non-ß cells. Moreover, ß cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing ß cells supporting a key role for Ngn3(+) insulin(-) cells in ß cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed ß cells as well as reprogramming of non-ß cells contribute to in vivo ß cell expansion in the injured pancreas of adult mice.

Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes.

AIMS/HYPOTHESIS: As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function. METHODS: Human BOEC, 5 × 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated. RESULTS: Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient. CONCLUSIONS/INTERPRETATION: The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.