Redeployment Among Primary Care Nurses During the COVID-19 Pandemic: A Qualitative Study.

Introduction: Throughout the COVID-19 pandemic, primary care nurses were often redeployed to areas outside of primary care to mitigate staffing shortages. Despite this, there is a scarcity of literature describing their perceptions of and experiences with redeployment during the pandemic. Objectives: This paper aims to: 1) describe the perspectives of primary care nurses with respect to redeployment, 2) discuss the opportunities/challenges associated with redeployment of primary care nurses, and 3) examine the nature (e.g., settings, activities) of redeployment by primary care nurses during the COVID-19 pandemic. Methods: In this qualitative study, semi-structured interviews were conducted with primary care nurses (i.e., Nurse Practitioners, Registered Nurses, and Licensed/Registered Practical Nurses), from four regions in Canada. These include the Interior, Island, and Vancouver Coastal Health regions in British Columbia; Ontario Health West region in Ontario; the province of Nova Scotia; and the province of Newfoundland and Labrador. Data related to redeployment were analyzed thematically. Results: Three overarching themes related to redeployment during the COVID-19 pandemic were identified: (1) Call to redeployment, (2) Redeployment as an opportunity/challenge, and (3) Scope of practice during redeployment. Primary care nurses across all regulatory designations reported variation in the process of redeployment within their jurisdiction (e.g., communication, policies/legislation), different opportunities and challenges that resulted from redeployment (e.g., scheduling flexibility, workload implications), and scope of practice implications (e.g., perceived threat to nursing license). The majority of nurses discussed experiences with redeployment being voluntary in nature, rather than mandated. Conclusions: Redeployment is a useful workforce strategy during public health emergencies; however, it requires a structured process and a decision-making approach that explicitly involves healthcare providers affected by redeployment. Primary care nurses ought only to be redeployed after other options are considered and arrangements made for the care of patients in their original practice area.

"Technology has allowed us to do a lot more but it's not necessarily the panacea for everybody": Family physician perspectives on virtual care during the COVID-19 pandemic and beyond.

INTRODUCTION: Early in the COVID-19 pandemic, Canadian primary care practices rapidly adapted to provide care virtually. Most family physicians lacked prior training or expertise with virtual care. In the absence of formal guidance, they made individual decisions about in-person versus remote care based on clinical judgement, their longitudinal relationships with patients, and personal risk assessments. Our objective was to explore Canadian family physicians' perspectives on the strengths and limitations of virtual care implementation for their patient populations during the COVID-19 pandemic and implications for the integration of virtual care into broader primary care practice. METHODS: We conducted semi-structured qualitative interviews with family physicians working in four Canadian jurisdictions (Vancouver Coastal health region, British Columbia; Southwestern Ontario; the province of Nova Scotia; and Eastern Health region, Newfoundland and Labrador). We analyzed interview data using a structured applied thematic approach. RESULTS: We interviewed 68 family physicians and identified four distinct themes during our analysis related to experiences with and perspectives on virtual care: (1) changes in access to primary care; (2) quality and efficacy of care provided virtually; (3) patient and provider comfort with virtual modalities; and (4) necessary supports for virtual care moving forward. CONCLUSIONS: The move to virtual care enhanced access to care for select patients and was helpful for family physicians to better manage their panels. However, virtual care also created access challenges for some patients (e.g., people who are underhoused or living in areas without good phone or internet access) and for some types of care (e.g., care that required access to medical devices). Family physicians are optimistic about the ongoing integration of virtual care into broader primary care delivery, but guidance, regulations, and infrastructure investments are needed to ensure equitable access and to maximize quality of care.

Embracing Paradigmatic Diversity in Nursing: The Stadium Model in Nursing.

Arguably, the quest for a central, unifying paradigm in nursing has distracted from moving disciplinary knowledge forward in an accessible, meaningful manner. In this discursive philosophical article, we uphold that multiparadigmatic research teams and diverse approaches inform effective nursing praxis. We provide an overview of our worldviews (dialectical pluralism, critical realism, humanism, and pragmatism) and their philosophical assumptions and describe how they are commensurate with nursing. We present the Stadium Model in Nursing as a metaphor to illustrate how various worldviews function like different sections of a stadium to offer diverse, yet important vantages of our nursing phenomena of interest.

"There's nothing like a good crisis for innovation": a qualitative study of family physicians' experiences with virtual care during the COVID-19 pandemic.

BACKGROUND: Prior to the pandemic, Canada lagged behind other Organisation for Economic Cooperation and Development countries in the uptake of virtual care. The onset of COVID-19, however, resulted in a near-universal shift to virtual primary care to minimise exposure risks. As jurisdictions enter a pandemic recovery phase, the balance between virtual and in-person visits is reverting, though it is unlikely to return to pre-pandemic levels. Our objective was to explore Canadian family physicians' perspectives on the rapid move to virtual care during the COVID-19 pandemic, to inform both future pandemic planning for primary care and the optimal integration of virtual care into the broader primary care context beyond the pandemic. METHODS: We conducted semi-structured interviews with 68 family physicians from four regions in Canada between October 2020 and June 2021. We used a purposeful, maximum variation sampling approach, continuing recruitment in each region until we reached saturation. Interviews with family physicians explored their roles and experiences during the pandemic, and the facilitators and barriers they encountered in continuing to support their patients through the pandemic. Interviews were audio-recorded, transcribed, and thematically analysed for recurrent themes. RESULTS: We identified three prominent themes throughout participants' reflections on implementing virtual care: implementation and evolution of virtual modalities during the pandemic; facilitators and barriers to implementing virtual care; and virtual care in the future. While some family physicians had prior experience conducting remote assessments, most had to implement and adapt to virtual care abruptly as provinces limited in-person visits to essential and urgent care. As the pandemic progressed, initial forays into video-based consultations were frequently replaced by phone-based visits, while physicians also rebalanced the ratio of virtual to in-person visits. Medical record systems with integrated capacity for virtual visits, billing codes, supportive clinic teams, and longitudinal relationships with patients were facilitators in this rapid transition for family physicians, while the absence of these factors often posed barriers. CONCLUSION: Despite varied experiences and preferences related to virtual primary care, physicians felt that virtual visits should continue to be available beyond the pandemic but require clearer regulation and guidelines for its appropriate future use.

"It was horrible for that community, but not for the way we had imagined": A qualitative study of family physicians' experiences of caring for communities experiencing marginalisation during COVID-19.

The COVID-19 response required family physicians (FPs) to adapt their practice to minimise transmission risks. Policy guidance to facilitate enacting public health measures has been generic and difficult to apply, particularly for FPs working with communities that experience marginalisation. Our objective was to explore the experiences of FPs serving communities experiencing marginalisation during COVID-19, and the impact the pandemic and pandemic response have had on physicians' ability to provide care. We conducted semi-structured qualitative interviews with FPs from four Canadian regions, October 2020 through June 2021. We employed maximum variation sampling and continued recruitment until we reached saturation. Interviews explored participants' roles/experiences during the pandemic, and the facilitators and barriers they encountered in continuing to support communities experiencing marginalisation throughout. We used a thematic approach to analyse the data. FPs working with communities experiencing marginalisation expressed the need to continue providing in-person care throughout the pandemic, often requiring them to devise innovative adaptations to their clinical settings and practice. Physicians noted the health implications for their patients, particularly where services were limited or deferred, and that pandemic response policies frequently ignored the unique needs of their patient populations. Pandemic-related precautionary measures that sought to minimise viral transmission and prevent overwhelming acute care settings may have undermined pre-existing services and superseded the ongoing harms that are disproportionately experienced by communities experiencing marginalisation. FPs are well placed to support the development of pandemic response plans that appreciate competing risks amongst their communities and must be included in pandemic planning in the future.

Family physicians' perspectives on the impact of COVID-19 on preventative care in primary care: findings from a qualitative study.

INTRODUCTION: Health system disruptions, caused by unexpected emergencies such as disease outbreaks, natural disasters, and cybercrimes, impact the delivery of routine preventative care. As comprehensive care providers, family physicians (FPs) devote significant time to prevention. However, without emergency and pandemic plans in place in primary care, FPs face added barriers to prioritizing and sustaining preventative care when health systems are strained, which was evident during the COVID-19 pandemic. This study aims to describe FPs' experiences providing preventative care during the COVID-19 pandemic and their perceptions of the impacts of disrupted preventative care in primary care settings. METHODS: Using a qualitative descriptive approach, we conducted semistructured interviews with FPs across 4 provinces in Canada (i.e. Newfoundland and Labrador, Nova Scotia, Ontario, British Columbia) between October 2020 and June 2021 as part of a larger multiple case study. These interviews broadly explored the roles and responsibilities of FPs during the COVID-19 pandemic. Interviews were coded thematically and codes from the larger study were analysed further using an iterative, phased process of thematic analysis. RESULTS: Interviews averaged 58 min in length (range 17-97 min) and FPs had a mean of 16.9 years of experience. We identified 4 major themes from interviews with FPs (n = 68): (i) lack of capacity and coordination across health systems, (ii) patient fear, (iii) impacts on patient care, and (iv) negative impacts on FPs. Physicians voiced concerns with managing patients' prevention needs when testing availability and coordination of services was limited. Early in the pandemic, patients were also missing or postponing their own primary care appointments. Change in the provision and coordination of routine preventative care had negative impacts on both patients and physicians, affecting disease incidence/progression, physician workload, and psychological wellbeing. CONCLUSION: During the COVID-19 pandemic, upstream care efforts were impacted, and FPs were forced to reduce their provision of preventative care. FPs contribute direct insight to primary care delivery that can support pandemic planning to ensure preventative care is sustained during future emergencies.

Nursing contributions to virtual models of care in primary care: a scoping review protocol.

INTRODUCTION: Since the onset of the COVID-19 pandemic, virtual care has gained increased attention, particularly in primary care for the ongoing delivery of routine services. Nurses have had an increased presence in virtual care and have contributed meaningfully to the delivery of team-based care in primary care; however, their exact contributions in virtual models of primary care remain unclear. The Nursing Role Effectiveness Model, applied in a virtual care and primary care context, outlines the association between structural variables, nursing roles and patient outcomes. The aim of this scoping review is to identify and synthesise the international literature surrounding nurse contributions to virtual models of primary care. METHODS AND ANALYSIS: The Joanna Briggs Institute scoping review methodology will guide this review. We performed preliminary searches in April 2022 and will use CINAHL, MEDLINE, Embase and APA PsycInfo for the collection of sources for this review. We will also consider grey literature, such as dissertations/theses and organisational reports, for inclusion. Studies will include nurses across all designations (ie, nurse practitioners, registered nurses, practical nurses). To ensure studies capture roles, nurses should be actively involved in healthcare delivery. Sources require a virtual care and primary care context; studies involving the use of digital technology without patient-provider interaction will be excluded. Following a pilot test, trained reviewers will independently screen titles/abstracts for inclusion and extract relevant data. Data will be organised using the Nursing Role Effectiveness Model, outlining the virtual care and primary care context (structure component) and the nursing role concept (process component). ETHICS AND DISSEMINATION: This review will involve the collection and analysis of secondary sources that have been published and/or are publicly available. Therefore, ethics approval is not required. Scoping review findings will be published in a peer-reviewed journal and presented at relevant conferences, targeting international primary care stakeholders.

Hindsight Is 2020: A Graduate Student Perspective.

The year 2020 was unpredictable and brought about unimaginable change for our world, disrupting operations within the nursing profession and healthcare systems at large. In this discussion paper, we revisit a report from the Canadian Nurses Association, Toward 2020: Visions for Nursing (Villeneuve and MacDonald 2006), from a graduate student perspective. In this 2006 report, the authors presented a series of predictions for the preferred future of nursing in Canada in 2020. Even without the pandemic, the pre-existing trends in healthcare and nursing did not favour success for the visions presented in this national nursing report. Now, two years after 2020, we examine the extent to which these predictions held true in the following areas: health systems, nursing practice, nursing workforce, nursing education and nursing regulation. We conclude that most of the preferred scenarios were unmet or partially met, and argue that it is critical to enact relevant preferred scenarios now. While the deleterious effects of the pandemic will be felt by the nursing profession for years, these experiences did not hinder our collective ability to lead change in Canada. We offer insights to provide recommendations for nursing actions toward a healthier future for Canadians. The best of nursing in Canada is within sight.

Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder.

OBJECTIVES: Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder. METHODS: We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n = 207), in patients with bipolar disorder without a recent onset of psychosis (n = 226), and in patients with bipolar disorder with a recent onset of psychosis (n = 38). We compared ASCA levels to antibodies against gluten, casein, Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), influenza A, influenza B, measles, and Toxoplasma gondii. RESULTS: Elevated ASCA conferred a 3.5-4.4-fold increased odds ratio of disease association (age-, race-, and gender-corrected multinomial logistic regressions, p ≤ 0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar disorder groups (R(2)  = 0.29-0.59, p ≤ 0.0005), and with measles and T. gondii immunoglobulin G (IgG) in the recent onset psychosis bipolar disorder group (R(2)  = 0.31-0.36, p ≤ 0.004-0.01). CONCLUSIONS: Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggest a GI comorbidity in at least a subgroup of individuals with bipolar disorder. Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder.

Antibodies to Toxoplasma gondii in individuals with mania.

OBJECTIVES: Increased rates of infection with Toxoplasma gondii have been found in individuals with schizophrenia as compared to control groups but this issue has not been studied in mania. METHODS: We measured immunoglobulin G (IgG) and IgM class antibodies to T. gondii in 57 individuals with mania who were assessed at up to three time-points. We also measured these antibodies in 743 individuals in other psychiatric groups and in 314 non-psychiatric controls. T. gondii antibody levels were compared among groups by multivariate analyses. IgG class and IgM class antibodies to cytomegalovirus were also measured in the same samples. T. gondii antibody levels were also compared over time in the mania group. RESULTS: The mania group had a significantly elevated level of IgM antibodies to T. gondii as compared to the control individuals without a psychiatric diagnosis [odds ratio (OR) = 2.33, p < 0.04 at hospital admission; and OR = 2.32, p < 0.02 at study entry during the hospital stay]. Elevated IgM class antibodies to T. gondii were not found in individuals with the other psychiatric diagnoses. We also did not find an increased level of IgG class antibodies to T. gondii or IgG or IgM class antibodies to CMV in the individuals with mania. Within the mania group, there was a significant difference between the prevalences of increased levels of T. gondii IgM at the baseline and the follow-up time-point (t = 2.97, p < 0.003). CONCLUSIONS: Infection with T. gondii may confer risk for mania.

A combined marker of inflammation in individuals with mania.

BACKGROUND: Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers. METHODS: A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up. Also assessed were 207 non-psychiatric controls and 330 individuals with recent onset psychosis, multi-episode schizophrenia, or bipolar disorder depression. A combined inflammation score was calculated by factor analysis of the levels of class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason-Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among groups were compared by multivariate analyses. The inflammation score of the mania group at evaluation was studied as a predictor of re-hospitalization in the follow-up period. RESULTS: The combined inflammation score of the mania group at hospital admission and at evaluation differed significantly from that of the non-psychiatric controls (t=3.95, 4.10, p<.001). The inflammation score was significantly decreased at six month follow-up (F=5.85, p=0.004). There were not any significant differences in the inflammation scores of any of the other psychiatric groups and that of the controls. Within the mania group, an elevated inflammation score at evaluation predicted re-hospitalization (Hazard ratio=7.12, p=.005). CONCLUSIONS: Hospitalization for mania is associated with immune activation. The level of this activation is predictive of subsequent re-hospitalization. Interventions for the modulation of inflammation should be evaluated for the therapy of individuals with mania.

Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder.

BACKGROUND: Some individuals with bipolar disorder have cognitive deficits even when euthymic. In previous studies, we found an association between elevated levels of C-reactive protein (CRP), a marker of inflammation, and reduced cognitive functioning in schizophrenia. This issue has not been examined in bipolar disorder. METHODS: We measured the levels of high sensitivity CRP in serum samples from 107 individuals with bipolar disorder. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Part A and WAIS Information and Letter Number Sequencing. We estimated the odds of RBANS scores <=70 for participants whose CRP levels were above the 75th and the 90th percentile of the level of non-psychiatric controls. We also examined the association between cognitive scores and CRP levels. Covariates included demographic factors, mood symptom severity, cigarette smoking status, and body mass index. RESULTS: There was a significantly increased odds of low RBANS total score for individuals who had a CRP level higher than the 90th percentile (OR=4.32, p=.018) and the 75th percentile (OR=3.07, p=.04)) of the control group. There was an inverse relationship between CRP levels and performance on RBANS total (t=-2.48, p=.015); RBANS immediate memory (t=-2.16, p=.033); RBANS attention (t=-2.18, p=.032); RBANS language (t=-2.13, p=.036); Trail Making A (t=-2.39, p=.019). LIMITATIONS: Factors which we did not measure such as diet, allergen exposure, and underlying autoimmune disorders may contribute to CRP levels. CONCLUSIONS: Inflammation may play a major role in the cognitive deficits associated with bipolar disorder.

Cigarette smoking among persons with schizophrenia or bipolar disorder in routine clinical settings, 1999-2011.

OBJECTIVE: This study examined the prevalence of cigarette smoking and the quantity of cigarettes consumed by individuals with schizophrenia or bipolar disorder and by those with no psychiatric disorder in the period 1999-2011. METHODS: A total of 991 individuals with schizophrenia, bipolar disorder, or no psychiatric illness provided information about their cigarette smoking at recruitment into a research study for which they were selected without regard to their smoking status. Differences among groups and trends over time among new enrollees were examined with multivariate models. Regression analyses were used to compare smoking between the schizophrenia and bipolar disorder groups. RESULTS: There were marked differences in the prevalence of smoking and in the quantity of cigarettes consumed among the diagnostic groups. Overall, 64% of individuals with schizophrenia, 44% with bipolar disorder, and 19% without psychiatric illness reported that they were current smokers. These group differences remained fairly constant over the observation period, and there were no statistically significant time trends in smoking or cigarette consumption after adjustment for demographic covariates. Within the psychiatric illness groups, smoking and cigarette consumption were significantly associated with less education, a history of substance abuse, longer illness duration, Caucasian race, and schizophrenia diagnosis but not with psychiatric symptom severity. CONCLUSIONS: The prevalence of smoking has remained alarmingly high among individuals with schizophrenia and bipolar disorder in routine psychiatric settings. Concerted efforts are urgently needed to promote smoking cessation in these groups.

C-reactive protein is elevated in schizophrenia.

BACKGROUND: Increased levels of inflammatory markers have been reported in schizophrenia, but few studies have examined levels of high sensitivity C-reactive protein (CRP), a non-specific inflammatory marker. METHODS: Levels of high sensitivity CRP were measured in individuals with schizophrenia, bipolar disorder, and non-psychiatric controls. Linear regression analyses were used to compare the CRP levels among the three groups adjusting for demographic and clinical variables. Logistic regression analyses were used to determine the odds ratios associated with elevated levels of CRP, defined as >=75th and 90th percentile in the controls. RESULTS: The sample consisted of 715 individuals: 295 with schizophrenia, 192 with bipolar disorder, and 228 without a psychiatric disorder. The levels of CRP in the schizophrenia group, but not in the bipolar disorder group, were significantly increased compared to controls adjusting for age, gender, race, maternal education, smoking status, and Body Mass Index (BMI) (t=3.78, p=<.001). The individuals with schizophrenia had significantly increased odds of having elevated levels of CRP relative to both the 75th and 90th percentile levels of the controls adjusting for the same covariates (OR 1.79, 95% CI 1.14, 2.82; p=.012; OR 2.76, 95% CI 1.58, 4.83, p=<.001). In the multivariate linear and logistic regression analyses, levels of CRP were also associated with BMI and female gender. CONCLUSIONS: Individuals with schizophrenia may be at risk for the adverse health consequences associated with elevated CRP in the overall population. Trials of interventions directed at lowering the level of CRP and other inflammatory markers are indicated.

Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia.

Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known. Food sensitivities characterized by elevated IgG antibodies to bovine milk caseins and wheat glutens have been reported in individuals with schizophrenia. Here, we examined the extent to which these food products might comprise the antigen component of complement C1q immune complexes in individuals with recent onset schizophrenia (n=38), non-recent onset schizophrenia (n=61) and non-psychiatric controls (n=63). C1q seropositivity was significantly associated with both schizophrenia groups (recent onset, odds ratio (OR)=8.02, p≤0.008; non-recent onset, OR=3.15, p≤0.03) compared to controls (logistic regression models corrected for age, sex, race and smoking status). Casein- and/or gluten-IgG binding to C1q was significantly elevated in the non-recent onset group compared to controls (OR=4.36, p≤0.01). Significant amounts of C1q-casein/gluten-related immune complexes and C1q correlations with a marker for gastrointestinal inflammation in non-recent onset schizophrenia suggests a heightened rate of food antigens in the systemic circulation, perhaps via a disease-associated altered intestinal permeability. In individuals who are in the early stages of disease onset, C1q activation may reflect the formation of immune complexes with non-casein- or non-gluten-related antigens, the presence of C1q autoantibodies, and/or a dissociated state of immune complex components. In conclusion, complement activation may be a useful biomarker to diagnose schizophrenia early during the course of the disease. Future prospective studies should evaluate the impacts of casein- and gluten-free diets on C1q activation in schizophrenia.

Antibodies to the glutamate receptor in mania.

BACKGROUND: There is evidence that the glutamatergic system is involved in the pathophysiology of mania. Antibodies to the NR2 subunits of the N-methyl-D-aspartate (NMDA) receptor have been shown to adversely affect glutamate functioning. METHODS: We measured serum antibodies to the NR2 peptide of the NMDA receptor in 60 individuals with different subtypes of mania, including schizoaffective cases, who were assessed at up to three time points. We also measured these antibodies in 295 individuals in other psychiatric groups and in 170 non-psychiatric controls. NR2 antibody levels were compared among groups by multivariate analyses and within the mania group by repeated measures analysis of variance. RESULTS: Individuals with mania had increased levels of antibodies to the NR2 peptide compared to levels in non-psychiatric controls when measured at the time of admission (t = 2.99, p = 0.003) and the time of evaluation (t = 2.57, p = 0.010), but not at follow-up six months later. The levels of antibodies in individuals in other psychiatric groups did not differ significantly from the levels measured in the control population. Within the mania group, there was a significant decrease in antibody levels over the three time points of the study (F = 5.4, df = 2, p = 0.0067). CONCLUSIONS: NR2 antibodies are elevated during the acute phase of mania but not at follow-up. Our findings support a role for antibodies to the NMDA receptor in the pathogenesis of acute mania.

Antibodies to retroviruses in recent onset psychosis and multi-episode schizophrenia.

BACKGROUND: Immunological abnormalities involving the upregulation of endogenous retroviruses have been associated with schizophrenia in small studies. METHODS: Blood samples from 666 individuals (163 with recent onset psychosis, 268 with multi-episode schizophrenia, and 235 controls) were assayed for IgG antibodies to murine leukemia virus (MuLV), Mason-Pfizer monkey virus (MPMV), and feline immunodeficiency virus (FIV) by enzyme immunoassay utilizing whole virus and viral components. Antibody levels in the psychiatric groups were compared to controls by multivariate linear regression. Odds ratios associated with increased antibody levels were calculated based on values ≥ 75th percentile of the controls. Samples were also tested for antibodies to viral proteins by Western blotting and for DNA from infectious retroviruses by real time PCR. Homology between the target virus and the prototype human genome was determined using sequence analysis methods. RESULTS: Compared with controls, individuals with recent onset of psychosis had increased levels of antibodies to MPMV and MuLV (both p<.001 adjusted for covariates), and increased antibody levels for defined portions of the MPMV and MuLV gag, pol and env proteins. The specificity of these antibodies was confirmed by Western blotting. Individuals with multi-episode schizophrenia did not show elevated antibody levels to any of the retroviruses measured. Infectious retroviruses were not detected in the blood of any participants. Homology analyses indicated that there are multiple regions of the human genome homologous with MPMV and MuLV proteins, the highest being with the MuLV gag protein. CONCLUSIONS: Antibodies to retroviral proteins are elevated in individuals with recent onset psychosis but not in individuals with multi-episode schizophrenia. The immunopathological consequences of this antibody response should be the subject of additional studies.

Markers of gluten sensitivity in acute mania: a longitudinal study.

Increased levels of antibodies to gliadin, which is derived from the wheat protein gluten, have been reported in schizophrenia and bipolar disorder in cross-sectional studies. We examined longitudinally the levels of antibody reactivity to gliadin in acute mania. The sample included 60 individuals assessed during a hospital stay for acute mania, 39 at a 6-month follow-up, and a sample of 143 non-psychiatric controls. Antibodies to gliadin were measured by enzyme immunoassay. The relationship of the antibodies to the clinical course of mania was analyzed by the use of regression models. Individuals with mania had significantly increased levels of IgG antibodies to gliadin, but not other markers of celiac disease, at baseline compared with controls in multivariate analyses. However, these levels were not significantly different from those of controls at the six month follow-up. Among the individuals with mania, elevated levels at follow-up were significantly associated with re-hospitalization in the 6-month follow-up period. The monitoring and control of gluten sensitivity may have significant effects on the management of individuals hospitalized with acute mania.

Gastrointestinal inflammation and associated immune activation in schizophrenia.

Immune factors are implicated in normal brain development and in brain disorder pathogenesis. Pathogen infection and food antigen penetration across gastrointestinal barriers are means by which environmental factors might affect immune-related neurodevelopment. Here, we test if gastrointestinal inflammation is associated with schizophrenia and therefore, might contribute to bloodstream entry of potentially neurotropic milk and gluten exorphins and/or immune activation by food antigens. IgG antibodies to Saccharomyces cerevisiae (ASCA, a marker of intestinal inflammation), bovine milk casein, wheat-derived gluten, and 6 infectious agents were assayed. Cohort 1 included 193 with non-recent onset schizophrenia, 67 with recent onset schizophrenia and 207 non-psychiatric controls. Cohort 2 included 103 with first episode schizophrenia, 40 of whom were antipsychotic-naïve. ASCA markers were significantly elevated and correlated with food antigen antibodies in recent onset and non-recent onset schizophrenia compared to controls (p≤0.00001-0.004) and in unmedicated individuals with first episode schizophrenia compared to those receiving antipsychotics (p≤0.05-0.01). Elevated ASCA levels were especially evident in non-recent onset females (p≤0.009), recent onset males (p≤0.01) and in antipsychotic-naïve males (p≤0.03). Anti-food antigen antibodies were correlated to antibodies against Toxoplasma gondii, an intestinally-infectious pathogen, particularly in males with recent onset schizophrenia (p≤0.002). In conclusion, gastrointestinal inflammation is a relevant pathology in schizophrenia, appears to occur in the absence of but may be modified by antipsychotics, and may link food antigen sensitivity and microbial infection as sources of immune activation in mental illness.

Additive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia.

OBJECTIVES: We investigated the effect of elevated levels of C-reactive protein (CRP) and exposure to Herpes simplex virus type 1 (HSV-1) on the severity of cognitive impairment in individuals with schizophrenia. METHODS: We measured the levels of CRP and of antibodies to HSV-1 in serum samples from 588 individuals with schizophrenia by enzyme immunoassay tests. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). The effects of HSV1 and CRP on cognitive functioning were analyzed with linear and logistic regression analyses adjusting for demographic and clinical variables. RESULTS: The individuals with elevated CRP levels and HSV-1 seropositivity had lower RBANS cognitive scores. The strongest effect was found in individuals who had both serological evidence of HSV-1 exposure and elevated levels of CRP. These individuals had odds of 2.35 to have an RBANS Total score<=60 as compared to individuals who were HSV-1 seronegative and who did not have elevated levels of CRP (p=.002). The risks of decreased cognitive functioning associated with HSV-1 exposure and elevated levels of CRP were independent and additive. There was no effect of HSV-1 exposure and CRP levels on the severity of symptoms as measured by the PANSS (all p>.5). CONCLUSIONS: Elevated levels of CRP and exposure to HSV-1 are associated with the severity of cognitive impairment in schizophrenia. These findings indicate that infection and inflammation may play a major role in the cognitive deficits associated with schizophrenia.