C-Reactive Protein (CRP): A Potent Inflammation Biomarker in Psychiatric Disorders.

An increasing number of studies have investigated the role of inflammation in psychiatric disorders, by demonstrating how an altered/dysfunctional immunological and inflammatory system may underpin a psychiatric condition. Particularly, several studies specifically investigated the role of a neuroinflammatory biomarker, named C-reactive protein (CRP), in psychiatric disorders. Overall, even though scientific literature so far published still does not appear definitive, CRP is more likely reported to be elevated in several psychiatric disorders, including schizophrenia, mood disorders, anxiety disorders and post-traumatic stress disorder. Moreover, a low-grade inflammation (CRP >3 mg/L) has been more likely observed in a subgroup of patients affected with a more severe psychopathological symptomatology, more treatment resistance and worst clinical mental illness course, strengthening the hypothesis of the need for a different clinical and prognostic characterization based on this concomitant neuroinflammatory predisposition. However, even though further research studies are needed to confirm this preliminary evidence, CRP may represent a potential clinical routine biomarker which could be integrated in the clinical routine practice to better characterize clinical picture and course as well as address clinicians towards a personalized treatment.

Exploring the association between lifetime traumatic experiences and positive psychotic symptoms in a group of long-stay patients with schizophrenia: the mediating effect of depression, anxiety, and distress.

BACKGROUND: Positive psychotic symptoms of schizophrenia are generally characterized by hallucinations and delusions. We propose to assess the relationship between total composite trauma and positive psychotic symptoms, along with the mediation effect of cognition, fear of COVID-19, insomnia, anxiety, distress, and depression of Lebanese patients with schizophrenia. METHODS: A cross-sectional study was carried out, between June and July 2021, by deriving data from 155 long-stay in-patients diagnosed with schizophrenia. RESULTS: Depression, anxiety, and distress but not cognitive impairment, insomnia, and fear of COVID-19) mediated the association between lifetime traumatic experiences and positive psychotic symptoms. Higher traumatic experiences were associated with greater depression, anxiety, and distress, indicating a significant positive total effect on positive psychotic scores. Moreover, higher depression, anxiety, and distress were significantly associated with higher positive psychotic symptoms. CONCLUSION: Our results contribute to the existing knowledge by suggesting other possible intervention paths through mediating factors. Interventions that improve anxiety, depression, and distress severity may be effective in reducing positive psychotic symptoms among patients with schizophrenia having experienced lifetime trauma.

The cultural epidemiology of stigma among people with schizophrenia : Adaptation and cross-cultural validation of the Explanatory Model Interview Catalogue (EMIC), in Dialectal Arabic (Darija), Morocco.

INTRODUCTION: Stigma underlies the violation of certain social, economic, and cultural rights of patients with schizophrenia, including their access to treatment and care. Measurement of stigma remains as complex and multifaceted as the phenomenon itself. Several measurement tools are available to assess the prevalence, intensity and qualities of stigma. The aim of the study was to carry out a cross-cultural adaptation of the Explanatory Model Interview Catalogue (EMIC), in the Moroccan Arabic dialect commonly known as "Darija". PATIENTS AND METHOD: The study was conducted in three psychiatric departments of public hospitals in the Souss-Massa region, located in southern Morocco. For the diagnosis of schizophrenia, the study was based on the decisions of the psychiatrists practicing at the study sites. The cross-cultural adaptation in Moroccan Darija of the stigma scale developed by Michel Weiss in the EMIC was carried out according to the six-step scientific method developed by Dorcas et al. RESULTS: Cronbach's alpha (internal consistency) was 0.845. Convergent validity determined by Pearson's coefficient showed a significant inter-item correlation and the intra-class correlation coefficient (test-retest) was 0.975 (0.993; 0.991). The item added in relation to the COVID-19 situation presented psychometric values similar to the others. CONCLUSION: The Darija version is culturally acceptable and can be used to approach the phenomenon of stigmatization in Morocco.

Certain Aspects of Immunopychiatry.

Immunopsychiatry is based on the assumption that schizophrenia, bipolar disorders, and major depressive disorders are related with atypical immune reactions or inflammatory processes. It has also been suggested that the neurotoxic effects of COVID-19 due to the perverted autoimmune reaction could offer fresh acumens into psychotic process. Even acute psychotic symptoms have a subtle pre-psychotic phase and unless treatments are aimed at this preceding phase, newer therapies are not going to achieve their targets. Identifying biosignatures of psychotic disorders lead to better understanding of the etiological mechanism involved in such disorders and aid early diagnostic assays. Interestingly, the search for biomarkers also stimulates new experimental treatment strategies as evidenced by the experiments of newer immunological therapies for psychotic disorders. Characterizing biosignatures are thought to play a significant role in the early detection, treatment, and implementation of preventive strategies in psychotic disorders. The search for identifying biosignatures should go hand in hand with newer experimental therapies for psychotic disorders for the benefit of introducing treatments at an early stage of psychosis development. The identification of biomarkers may lead to a shift from symptom based diagnostic category into subtypes based on immunological alterations and brain biology and such a change might have an advantage to make more precise diagnosis aiding better treatment. The field of immunopsychiatry requires more research to put their findings in context.

Psychiatric symptoms before and after COVID-19 vaccination: A cohort study of hospitalized schizophrenia patients.

This study aimed to examine the impact of COVID-19 vaccination on the psychiatric symptoms of hospitalized schizophrenia patients and to evaluate the association between the severity of psychiatric symptoms and the COVID-19 vaccination decision. We assessed the psychiatric symptoms of 330 hospitalized schizophrenia patients who accepted the vaccine and 114 patients who declined the vaccine option with PANSS before and after vaccination. We showed that the unwillingness to receive the vaccine is correlated with a higher level of psychiatric symptoms. COVID-19 vaccination is associated with slight deterioration of the schizophrenia symptoms of elderly hospitalized patients.

Challenges and Strategies for the Recruitment of Patients With Schizophrenia in a Research Setting.

BACKGROUND: With numerous potentially novel targets and pharmacodynamic biomarkers for schizophrenia entering late-stage testing, the next decade will bring an urgent need for well-conducted clinical trials. A critically important step for the successful execution of clinical research trials is timely and appropriate recruitment of participants. Patients with schizophrenia can be especially challenging to recruit because of the disability inherent in psychotic spectrum disorders. Research on how best to recruit for clinical trials is understudied. Clearly defining a model for recruitment procedures would be valuable for researchers and, by extension, the patient populations that may benefit from the insight gained by future clinical research. METHODS: This article aims to offer suggestions for recruitment based on years of experience at the Columbia Schizophrenia Research Clinic (CSRC), a hub for clinical trials focusing on the etiology and treatment of various psychotic disorders. RESULTS: The present report provides practical, step-by-step recommendations for implementing the highly effective CSRC recruitment model, including the benefits of 2 recruitment initiatives that were instituted in 2018: hiring a dedicated recruiter and targeted chart reviews at affiliated clinics. Other topics discussed include our umbrella protocol and database, advertising, and tips for collaborating with external sites. CONCLUSIONS: Despite ongoing complications from coronavirus disease 2019, these strategies have been successful, increasing the rate of both consents and study enrollments by approximately 40% and enabling the CSRC to conduct multiple studies simultaneously.

The effect of stigmatization education on the social distancing of nursing students toward patients with a diagnosis of schizophrenia.

PURPOSE: To assess the effect of a program designed to reduce nursing students' social distancing from individuals diagnosed with schizophrenia. METHOD: This experimental study was designed using a pretest, a posttest, and a control group. All participants were nursing students, of which 25 were included in the intervention group and 23 were placed in the control group. A 13-week program was offered to the intervention group. The measuring instruments consisted of a personal information form and the Social Distance Scale. Data were analyzed using the two-way repeated measures analysis of variance. FINDINGS: A significant difference was found between the two groups. CONCLUSION: The Education Program on Stigmatization in Schizophrenia is an effective intervention that reduces the social distance of nursing students from individuals diagnosed with schizophrenia.

Factors associated with COVID-19 Infection among a national population of individuals with schizophrenia or schizoaffective disorder in the United States.

BACKGROUND: Individuals with schizophrenia are a vulnerable and under-served population who are also at risk for severe morbidity and mortality following COVID-19 infection. Our research was designed to identify factors that put individuals with schizophrenia at increased risk of COVID-19 infection. METHODS: This study was a retrospective cohort analysis of medical and pharmacy claims among 493,796 individuals residing in the United States with schizophrenia or schizoaffective disorder, between January 1, 2019 and June 30, 2020. A confirmed diagnosis of COVID-19 infection by September 30, 2020 was regressed on demographics, social determinants, comorbidity, and pre-pandemic (December 2019 - February 2020) healthcare utilization characteristics. RESULTS: A total of 35,249 (7.1%) individuals were diagnosed with COVID-19. Elevated odds of COVID-19 infection were associated with age, increasing consistently from 40-49 years (OR: 1.16) to 80+ years (OR:5.92), male sex (OR: 1.08), Medicaid (OR: 2.17) or Medicare (OR: 1.23) insurance, African American race (OR: 1.42), Hispanic ethnicity (OR: 1.23), and higher Charlson Comorbidity Index. Select psychiatric comorbidities (depressive disorder, adjustment disorder, bipolar disorder, anxiety, and sleep-wake disorder) were associated with elevated odds of infection, while alcohol use disorder and PTSD were associated with lower odds. A pre-pandemic psychiatry (OR:0.56) or community mental health center (OR:0.55) visit were associated with lower odds as was antipsychotic treatment with long-acting injectable antipsychotic (OR: 0.72) and oral antipsychotic (OR: 0.62). CONCLUSIONS: Among individuals with schizophrenia, risk of COVID-19 infection was substantially higher among those with fewer economic resources, with greater medical and psychiatric comorbidity burden, and those who resided in African American or Hispanic communities. In contrast, individuals actively engaged in psychiatric treatment had substantially lower likelihood of infection. These results provide insights for healthcare providers that can translate into improved identification of at-risk individuals and interventions to reduce the risk and consequences of COVID-19 infection.

Clozapine and COVID-19: A Case Report and Clinical Considerations.

BACKGROUND: The emergence of coronavirus SARS-CoV-2, and the subsequent global epidemic of COVID-19, brought with it innumerable new clinical experiences across all medical specialties, and psychiatry is no exception. Individuals with serious mental illness, in particular schizophrenia and related disorders, may be especially susceptible to coronavirus infection given the overlapping risk factors of vulnerable sociodemographic status, increased challenges with quarantining requirements, and limited compliance with "respiratory etiquette." The case presented here describes a patient with schizophrenia who was being managed on clozapine and who developed symptomatic COVID-19 infection. Special care was taken to ensure that potential interactions between clozapine and the associated COVID-19 treatments were safe for the patient's mental and physical wellbeing. CASE PRESENTATION: A 71-year-old schizophrenic Caucasian male is being managed with clozapine. While hospitalized, the patient was screened positive for COVID-19 and was admitted to the ICU due to his declining respiratory status. He was treated with both remdesivir and prednisone. He was able to fully recover from his COVID-19 infection. CONCLUSION: The authors review the clinical characteristics of the case, highlighting both the overlapping synergistic effects and antagonistic influences of clozapine therapy in combination with COVID-19 and its associated treatments. A review of the literature offers an opportunity to examine various frameworks for individualized clinical decision-making while making the case for greater epidemiologic research into the optimal management of individuals with a psychotic disorder who are diagnosed with COVID-19 infection.

Schizophrenia population health management: perspectives of and lessons learned from population health decision makers.

BACKGROUND: Despite therapeutic advances for patients with schizophrenia, improving patient outcomes and reducing the cost of care continue to challenge formulary decision makers. OBJECTIVES: To (1) understand the perspectives of formulary decision makers on challenges to optimal schizophrenia population management and (2) identify best practices and recommendations for mitigating these challenges. METHODS: This mixed-methods study, conducted in a double-blind manner, comprised in-depth telephone interviews with formulary decision makers from February through May 2020, and a web-based follow-on survey that was sent to all participants in October 2020. US-based formulary decision makers were recruited if they were directly involved in schizophrenia drug formulary or coverage decision making for national or regional payers, health systems, or behavioral health centers. Formulary decision makers' perceptions of challenges, policies, and programs related to schizophrenia population health management were assessed generally and in the context of the COVID-19 pandemic. RESULTS: 19 formulary decision makers participated in the interviews and 18 (95%) completed the survey. Participants reported a spectrum of patient- and payer-driven challenges in schizophrenia population health management, including medication nonadherence, high pharmacy and medical costs, and frequent hospitalizations and emergency department visits. Participants noted that COVID-19 had worsened all identified challenges, although patient unemployment (mean score of 2.00 on a scale of 1 [made much worse] to 5 [made much better]) and reduced access to psychiatric care (mean score, 2.12) were most negatively affected. The most common strategies implemented in order to improve schizophrenia population health management included case management (89%), telemedicine (83%), care coordination programs (72%), strategies to mitigate barriers to accessing medication (61%), and providing nonmedical services to address social determinants of health (56%). Participants noted that, ideally, all treatments for schizophrenia would be available on their formularies without utilization management policies in place in order to increase accessibility to medication, but cost to the health plans made that difficult. Whereas 61% of respondents believed that long-acting injectable antipsychotics (LAIs) were currently underused in their organizations, only 28% represented organizations with open access policies for LAIs. Participants believed that among patients with schizophrenia, LAIs were most beneficial for those with a history of poor or uncertain adherence to oral medications (mean score of 4.50 on a scale of 1 [not at all beneficial] to 5 [extremely beneficial]) and those with recurring emergency department visits and inpatient stays (mean score, 3.94). Study participants reported slightly increased use of LAIs (mean score of 3.17 on a scale of 1 [negatively impacted] to 5 [positively impacted]) among their patients with schizophrenia in response to the COVID-19 pandemic; 29% of participants reported easing access restrictions for LAIs. CONCLUSIONS: Participants described persisting challenges and various approaches intended to improve schizophrenia population health management. They also recommended strategies to optimize future health management for this population, including expanding programs to address social determinants of health and mitigating barriers to accessing treatment. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Roach, Graf, Pednekar, and Chou are employees of PRECISIONheor, which received financial support from Janssen Scientific Affairs, LLC, to conduct this study. Chou owns equity in Precision Medicine Group, the parent company of PRECISIONheor. Lin and Benson are employees of Janssen Scientific Affairs, LLC. Doshi has served as a consultant, advisory board member, or both, for Acadia, Allergan, Boehringer Ingelheim, Janssen, Merck, Otsuka, and Sage Therapeutics and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, Merck, Pfizer, PhRMA, Regeneron, Sanofi, and Valeant.

The COVID-19 Pandemic Introduces Diagnostic and Treatment Planning Complexity for Individuals at Clinical High Risk for Psychosis.

COVID-19 has led to a great deal of general suffering and an increased prevalence of psychiatric illness worldwide. Within the area of psychosis-risk syndromes, a highly heterogeneous clinical population, the picture is quite nuanced as the social restrictions resulting from the pandemic have reduced stress for some and increased it for others. Further, a number of pandemic-related societal and cultural changes have obfuscated the diagnostic and treatment landscape in this area as well. In this opinion article, we describe several prototypical cases, representative of presentations seen in our clinical high-risk (CHR) research programs. The cases highlight considerable clinical variability and, in addition, speak to the current complexities faced by diagnosticians and treatment providers. In addition to discussing these issues, this piece introduces potential solutions highlighting the promise of incorporating data-driven strategies to identify more homogenous CHR subtypes and employ precision medicine.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.

HOPES: An Integrative Digital Phenotyping Platform for Data Collection, Monitoring, and Machine Learning.

The collection of data from a personal digital device to characterize current health conditions and behaviors that determine how an individual's health will evolve has been called digital phenotyping. In this paper, we describe the development of and early experiences with a comprehensive digital phenotyping platform: Health Outcomes through Positive Engagement and Self-Empowerment (HOPES). HOPES is based on the open-source Beiwe platform but adds a wider range of data collection, including the integration of wearable devices and further sensor collection from smartphones. Requirements were partly derived from a concurrent clinical trial for schizophrenia that required the development of significant capabilities in HOPES for security, privacy, ease of use, and scalability, based on a careful combination of public cloud and on-premises operation. We describe new data pipelines to clean, process, present, and analyze data. This includes a set of dashboards customized to the needs of research study operations and clinical care. A test use case for HOPES was described by analyzing the digital behavior of 22 participants during the SARS-CoV-2 pandemic.

Anomaly detection to predict relapse risk in schizophrenia.

The integration of technology in clinical care is growing rapidly and has become especially relevant during the global COVID-19 pandemic. Smartphone-based digital phenotyping, or the use of integrated sensors to identify patterns in behavior and symptomatology, has shown potential in detecting subtle moment-to-moment changes. These changes, often referred to as anomalies, represent significant deviations from an individual's baseline, may be useful in informing the risk of relapse in serious mental illness. Our investigation of smartphone-based anomaly detection resulted in 89% sensitivity and 75% specificity for predicting relapse in schizophrenia. These results demonstrate the potential of longitudinal collection of real-time behavior and symptomatology via smartphones and the clinical utility of individualized analysis. Future studies are necessary to explore how specificity can be improved, just-in-time adaptive interventions utilized, and clinical integration achieved.

Association of Psychiatric Disorders With Mortality Among Patients With COVID-19.

Importance: To date, the association of psychiatric diagnoses with mortality in patients infected with coronavirus disease 2019 (COVID-19) has not been evaluated. Objective: To assess whether a diagnosis of a schizophrenia spectrum disorder, mood disorder, or anxiety disorder is associated with mortality in patients with COVID-19. Design, Setting, and Participants: This retrospective cohort study assessed 7348 consecutive adult patients for 45 days following laboratory-confirmed COVID-19 between March 3 and May 31, 2020, in a large academic medical system in New York. The final date of follow-up was July 15, 2020. Patients without available medical records before testing were excluded. Exposures: Patients were categorized based on the following International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnoses before their testing date: (1) schizophrenia spectrum disorders, (2) mood disorders, and (3) anxiety disorders. Patients with these diagnoses were compared with a reference group without psychiatric disorders. Main Outcomes and Measures: Mortality, defined as death or discharge to hospice within 45 days following a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result. Results: Of the 26 540 patients tested, 7348 tested positive for SARS-CoV-2 (mean [SD] age, 54 [18.6] years; 3891 [53.0%] women). Of eligible patients with positive test results, 75 patients (1.0%) had a history of a schizophrenia spectrum illness, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder. After adjusting for demographic and medical risk factors, a premorbid diagnosis of a schizophrenia spectrum disorder was significantly associated with mortality (odds ratio [OR], 2.67; 95% CI, 1.48-4.80). Diagnoses of mood disorders (OR, 1.14; 95% CI, 0.87-1.49) and anxiety disorders (OR, 0.96; 95% CI, 0.65-1.41) were not associated with mortality after adjustment. In comparison with other risk factors, a diagnosis of schizophrenia ranked behind only age in strength of an association with mortality. Conclusions and Relevance: In this cohort study of adults with SARS-CoV-2-positive test results in a large New York medical system, adults with a schizophrenia spectrum disorder diagnosis were associated with an increased risk for mortality, but those with mood and anxiety disorders were not associated with a risk of mortality. These results suggest that schizophrenia spectrum disorders may be a risk factor for mortality in patients with COVID-19.

[Immunopsychiatry and SARS-CoV-2 pandemic: Links and possible consequences]. / Immuno-psychiatrie et pandémie de SARS-CoV-2 : liens et possibles conséquences.

OBJECTIVE: The SARS-CoV-2 (or COVID-19) pandemic has been propagating since December 2019, inducing a drastic increase in the prevalence of anxious and depressive disorders in the general population. Psychological trauma can partly explain these disorders. However, since psychiatric disorders also have an immuno-inflammatory component, the direct effects of the virus on the host's immune system, with a marked inflammatory response, but also the secondary inflammation to these psychosocial stressors, may cause the apparition or the worsening of psychiatric disorders. We describe here the probable immunopsychiatric consequences of the SARS-CoV-2 pandemic, to delineate possible screening actions and care that could be planned. METHOD: Data from previous pandemics, and existing data on the psychopathological consequences of the SARS-CoV-2 pandemic, allowed us to review the possible immunopsychiatric consequences of the SARS-CoV-2 pandemic, on the gestational environment, with the risk of consecutive neurodevelopmental disorders for the fetus on one hand, on the children and adults directly infected being at increased risks of psychiatric disorders on the other hand. RESULTS: As in previous pandemics, the activation of the immune system due to psychological stress and/or to infection during pregnancy, might lead to an increased risk of neurodevelopmental disorders for the fetus (schizophrenia and autism spectrum disorders). Furthermore, in individuals exposed to psychological trauma and/or infected by the virus, the risk of psychiatric disorders, especially mood disorders, is probably increased. CONCLUSION: In this context, preventive measures and specialized care are necessary. Thus, it is important to propose a close follow-up to the individuals who have been infected by the virus, in order to set up the earliest care possible. Likewise, in pregnant women, screening of mood disorders during the pregnancy or the postpartum period must be facilitated. The follow-up of the babies born during the pandemic must be strengthened to screen and care for possible neurodevelopmental disorders.

The effect of childhood trauma on age of onset in patients with schizophrenia.

PURPOSE: Childhood trauma (CT) has been shown to affect the etiology and clinical features of schizophrenia. In this study, it was aimed to investigate the effects of CT on the age of onset (AoO) and clinical features of the disease by considering factors such as family history, head trauma, birth trauma, alcohol and substance abuse that may affect AoO of the disease. METHODS: The sample comprising 200 patients admitted to the outpatient and inpatient care at the Izmir Katip Çelebi University, Atatürk Education and Research Hospital psychiatry clinic, were included in the study. Socio-demographic information form, Positive and Negative Syndrome Scale (PANSS), Childhood Trauma Questionnaire-Short Form (CTQ-SF) and subscale of Mini-International Neuropsychiatric Interview (MINI) were applied. RESULTS: All types of trauma, except physical abuse, were found related to the disease onset age earlier. It was also detected that the factors of head trauma, birth complication, presence of an individual diagnosed with schizophrenia in the family and migration history were not related to AoO of the disease. On the other hand, it was found that physical, emotional and sexual abuses lead to more positive psychotic symptoms, and all types of CT increase the severity of disease and the risk of suicide. CONCLUSION: This study draws attention to the etiological importance of CT in schizophrenia as an environmental factor by showing that it affects AoO of the disease along with symptomatology. Future studies should focus on the pathogenesis of CT in schizophrenia and the interaction between CT and biological and genetic predisposition.