The Association Between Exposure to COVID-19 and Mental Health Outcomes Among Healthcare Workers

Due to the unprecedented impact of the COVID-19 pandemic on health care systems, there has been great interest in the mental wellbeing of healthcare workers. While most studies investigated mental health outcomes among frontline vs. non-frontline healthcare workers, little is known about the impact of various work-related variables. The present study aimed to examine the association between work-related [i.e., having contact with COVID-19 patients, being redeployed due to the pandemic and availability of sufficient personal protective equipment (PPE)] and subjective (i.e., worries about getting infected or infecting others) exposures and self-reported mental health outcomes (i.e., psychological distress, depressive symptoms, and posttraumatic stress symptoms). Between February and May 2021, 994 healthcare workers employed at a variety of healthcare settings in the Netherlands filled out an online survey as part of the COVID-19 HEalth caRe wOrkErS (HEROES) study. Mental health outcomes were measured using the General Health Questionnaire-12, the Patient Health Questionnaire-9, and the Primary Care PTSD Screen for DSM-5. Approximately 13% reported depressive symptoms, 37% experienced psychological distress, and 20% reported posttraumatic stress symptoms. Multilevel linear models consisted of three levels: individual (work-related and subjective exposures), healthcare center (aggregated redeployment and availability of sufficient PPE), and regional (cumulative COVID-19 infection and death rates). Worries about infection were associated with all three mental health outcomes, whereas insufficient PPE was associated with psychological distress and depressive symptoms. There were no differences in outcomes between healthcare centers or provinces with different COVID-19 infection and death rates. Our findings highlight the importance of adequate PPE provision and the subjective experience of the COVID-19 pandemic. These factors should be part of interventions aimed at mitigating adverse mental health outcomes among healthcare workers during the COVID-19 pandemic

Longitudinal association between motor and obsessive compulsive symptoms in patients with psychosis and their unaffected siblings

Little is known about the co-prevalence of obsessive compulsive symptoms (OCS) and motor symptoms in patients with psychotic disorders. Cross-sectional associations between OCS and motor symptoms were assessed at baseline and at 3years follow-up in patients (n=726) with psychotic disorders and in their unaffected siblings (n=761) from the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Furthermore, longitudinal associations between changes in OCS and motor symptoms were evaluated. At baseline, OCS was not associated with any motor symptom (akathisia, dyskinesia, parkinsonism or dystonia) in patients. At follow-up, patients with OCS reported significantly more akathisia. Dividing the patients into four groupsno OCS, OCS remission with OCS only at baseline, OCS de novo with OCS only at follow-up and a persistent OCS grouprevealed that the OCS de novo group already reported more akathisia at baseline compared to the no-OCS group. At follow-up, both the OCS de novo and the persistent OCS group reported more akathisia. These results remained significant after correcting for relevant confounders clozapine, GAF score, PANSS-negative score and IQ. Motor symptoms at baseline were significantly associated with OCS at follow-up, but not the other way around. In siblings, OCS at baseline was associated with akathisia, but this association was lost at follow-up. Results suggest that motor symptoms might precede co-occurring OCS in patients with psychotic disorders. However, no inference can be made about causality, and further prospective research is needed to investigate this assumption

Polygenic risk score for schizophrenia was not associated with glycemic level (HbA1c) in patients with non-affective psychosis: Genetic Risk and Outcome of Psychosis (GROUP) cohort study

Introduction: Type 2 diabetes (T2D) is a common comorbidity in patients with schizophrenia (SCZ). The underlying pathophysiologic mechanisms are yet to be fully elucidated, although it can be argued that shared genes, environmental factors or their interaction effect are involved. This study investigated the association between polygenic risk score of SCZ (PRSSCZ) and glycated haemoglobin (HbA1c) while adjusting for polygenic risk score of T2D (PRST2D), and clinical and demographic covariables. Methods: Genotype, clinical and demographic data of 1129 patients with non-affective psychosis were extracted from Genetic Risk and Outcome of Psychosis (GROUP) cohort study. The glycated haemoglobin (HbA1c) was the outcome. PRS was calculated using standard methods. Univariable and multivariable linear regression analyses were applied to estimate associations. Additionally, sensitivity analysis based on multiple imputation was done. After correction for multiple testing, a two-sided p-value ≤.003 was considered to discover evidence for an association. Results: Of 1129 patients, 75.8% were male with median age of 29 years. The mean (standard deviation) HbA1c level was 35.1 (5.9) mmol/mol. There was no evidence for an association between high HbA1c level and increased PRSSCZ (adjusted regression coefficient (aβ) = 0.69, standard error (SE) = 0.77, p-value =.37). On the other hand, there was evidence for an association between high HbA1c level and increased PRST2D (aβ = 0.93, SE = 0.32, p-value =.004), body mass index (aβ = 0.20, SE = 0.08, p-value =.01), diastolic blood pressure (aβ = 0.08, SE = 0.04, p-value =.03), late age of first psychosis onset (aβ = 0.19, SE = 0.05, p-value =.0004) and male gender (aβ = 1.58, SE = 0.81, p-value =.05). After multiple testing correction, there was evidence for an association between high HbA1c level and late age of first psychosis onset. Evidence for interaction effect between PRSscz and antipsychotics was not observed. The multiple imputation-based sensitivity analysis provided consistent results with complete case analysis. Conclusions: Glycemic dysregulation in patients with SCZ was not associated with PRSSCZ. This suggests that the mechanisms of hyperglycemia or diabetes are at least partly independent from genetic predisposition to SCZ. Our findings show that the change in HbA1c level can be caused by at least in part due to PRST2D, late age of illness onset, male gender, and increased body mass index and diastolic blood pressure

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.This work was supported by the Medical Research Council (G0901310) and the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z). This study was supported by the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London and by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust at King’s College London. Further support to EB: Mental Health Research UK’s John Grace QC award, BMA Margaret Temple grants 2016 and 2006, MRC—Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship, the NIHR Biomedical Research Centre at UCLH, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King’s College London. Further support to co-authors: The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to CI). The BMA Margaret Temple grant 2016 to JT. A 2014 European Research Council Marie Curie award to A Díez-Revuelta. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429. A Medical Research Council doctoral studentship to JH-S, IA-Z and AB. A Mental Health Research UK studentship to RM. VB is supported by a Wellcome Trust Seed Award in Science (200589/Z/16/Z). FWO Senior Clinical Fellowship to RvW. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organisations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Centre and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Groningen: University Medical Centre Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical centre The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en De Kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Centre Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundació (CI 2005-0308007), Fundacion Ramón Areces and Fundacion Marqués de Valdecilla (API07/011, API10/13). We thank Valdecilla Biobank for providing the biological PAFIP samples and associated data included in this study and for its help in the technical execution of this work; we also thank IDIVAL Neuroimaging Unit for its help in the acquisition and processing of imaging PAFIP data

Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis

Background Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. Methods We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltag

Clustering schizophrenia genes by their temporal expression patterns aids functional interpretation

Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia

Association of cognitive performance with clinical staging in schizophrenia spectrum disorders:a prospective 6-year follow-up study

Background: Clinical staging has been developed to capture the large heterogeneity in schizophrenia spectrum disorders. Including cognitive performance in the staging model may improve its clinical validity. Moreover, cognitive functioning could predict transition across stages. However, current evidence of the association between cognition and clinical staging is inconsistent. Therefore, we aim to assess whether cognitive parameters are associated with clinical stages in a large sample of patients with schizophrenia spectrum disorders and to identify cognitive markers at baseline that are associated with stage-transition at three and six-year follow-up. Methods: We applied the staging model of Fusar-Poli et al. (2017) in 927 patients with non-affective psychotic disorders, assessed at baseline, and after three and six-year follow-up. Cognitive performance was assessed with a standard test battery. Generalized linear mixed models were used to analyze associations of cognitive performance with staging and stage-transition at follow-up. Results: Findings showed that higher stages of illness were significantly associated with lower processing speed (F = 3.688, p = 0.025) and deficits in working memory (F = 6.365, p = 0.002) across assessments. No associations between cognitive parameters at baseline and stage-transition at three- and six-year follow-up were found. Conclusion: We conclude that processing speed and working memory were modestly associated with higher stages of illness in schizophrenia spectrum disorders, thereby slightly improving its clinical validity. However, associations were small and we found no evidence for predictive validity

The Association Between Exposure to COVID-19 and Mental Health Outcomes Among Healthcare Workers

Due to the unprecedented impact of the COVID-19 pandemic on health care systems, there has been great interest in the mental wellbeing of healthcare workers. While most studies investigated mental health outcomes among frontline vs. non-frontline healthcare workers, little is known about the impact of various work-related variables. The present study aimed to examine the association between work-related [i.e., having contact with COVID-19 patients, being redeployed due to the pandemic and availability of sufficient personal protective equipment (PPE)] and subjective (i.e., worries about getting infected or infecting others) exposures and self-reported mental health outcomes (i.e., psychological distress, depressive symptoms, and posttraumatic stress symptoms). Between February and May 2021, 994 healthcare workers employed at a variety of healthcare settings in the Netherlands filled out an online survey as part of the COVID-19 HEalth caRe wOrkErS (HEROES) study. Mental health outcomes were measured using the General Health Questionnaire-12, the Patient Health Questionnaire-9, and the Primary Care PTSD Screen for DSM-5. Approximately 13% reported depressive symptoms, 37% experienced psychological distress, and 20% reported posttraumatic stress symptoms. Multilevel linear models consisted of three levels: individual (work-related and subjective exposures), healthcare center (aggregated redeployment and availability of sufficient PPE), and regional (cumulative COVID-19 infection and death rates). Worries about infection were associated with all three mental health outcomes, whereas insufficient PPE was associated with psychological distress and depressive symptoms. There were no differences in outcomes between healthcare centers or provinces with different COVID-19 infection and death rates. Our findings highlight the importance of adequate PPE provision and the subjective experience of the COVID-19 pandemic. These factors should be part of interventions aimed at mitigating adverse mental health outcomes among healthcare workers during the COVID-19 pandemic

Economic evaluation of brief cognitive behavioural therapy for social activation in recent-onset psychosis

BACKGROUND: In schizophrenia spectrum disorders, negative symptoms (e.g. social withdrawal) may persist after initial treatment with antipsychotics, much affecting the quality of life (QOL) of patients. This health-economic study evaluated if a dedicated form of cognitive behaviour therapy for social activation (CBTsa) would reduce negative symptoms and improve QOL in an economically sustainable way. METHODS: A health-economic evaluation was conducted alongside a single-blind randomised controlled trial in two parallel groups: guideline congruent treatment as usual (TAU; n = 50) versus TAU augmented with adjunct CBTsa (n = 49). Outcomes were PANSS negative symptom severity and EQ-5D quality adjusted life years (QALYs) gained. The health-economic evaluation was conducted both from the societal and the health sector perspective. RESULTS: Both conditions showed improvement in the respective outcomes over the follow-up period of six months, but QALY gains were significantly higher in the CBTsa condition compared to the TAU condition. Treatment response rate (i.e. ≥ 5-point decrease on the PANSS) was not significantly different. However, the add-on CBT intervention was associated with higher costs. This did not support the idea that CBTsa is a cost-effective adjunct. Various sensitivity analyses attested to the robustness of these findings. CONCLUSIONS: In the Dutch context where TAU for psychosis is guideline congruent and well implemented there appears no added value for adjunct CBTsa. In other settings where the treatment for the schizophrenia spectrum disorders solely relies on antipsychotics, add-on CBTsa may lead to clinically superior outcomes, but it should still be evaluated if adjunct CBTsa therapy is a cost-effective alternative. TRIAL REGISTRATION: ClinicalTrials.gov registry under NCT03217955

Cognitive Behavioral Therapy for Social Activation in Recent-Onset Psychosis:Randomized Controlled Trial

Objective: Negative symptoms largely account for poor outcome in psychotic disorders but remain difficult to treat. A cognitive- behavioral approach to these symptoms showed promise in chronic schizophrenia patients. We explored whether a combination of group and individual treatment focused on social activation (CBTsa) could benefit patients recently diagnosed with a psychotic disorder. Method: A single-blind randomized controlled trial enrolled 99 participants recently diagnosed with schizophrenia or a related disorder that received treatment as usual (TAU; n = 50), or TAU plus CBTsa (n = 49). Negative symptoms (Brief Negative Symptom Scale) and social withdrawal (Positive and Negative Syndrome Scale) were primary outcomes. Secondary outcome measures included dysfunctional beliefs (Dysfunctional Attitudes Scale-Defeatist Performance Attitude), stigma Internalized Stigma of Mental Illness Scale (ISMIS), and symptom severity and functioning as measured with the Global Assessment of Functioning (GAF). Outcomes were compared directly posttreatment and at follow-up (6 months posttreatment). Results: Intention-to-treat analyses showed significant improvement in GAF symptoms (p = .02, d = 0.36) and a decrease in negative symptoms on trend level (p = .08, d==0.29) in CBTsa compared to TAU at posttreatment. These group differences were no longer apparent at 6 months follow-up. Social withdrawal and negative symptoms improved over time in both conditions. Conclusions: The current trial showed small positive effects on symptom severity posttreatment but did not demonstrate maintenance of longer-term effects in favor of the CBTsa group. Findings suggest that the treatment duration may have been too short to change dysfunctional beliefs, a potentially important maintaining factor of negative symptom severity. Longer intervention periods in later, more stable stages of the illness when intensive standard treatment has tapered off may yield more beneficial effects