Adjunctive probiotic microorganisms to prevent rehospitalization in patients with acute mania: A randomized controlled trial.

OBJECTIVE: Immunological abnormalities play a role in the pathophysiology of mania and have been associated with relapse. Probiotic organisms such as Lactobacilli and Bifidobacteria modulate inflammation in humans and animal models. The trial examined whether the administration of probiotic organisms prevents psychiatric rehospitalizations in patients recently discharged following hospitalization for mania. METHODS: Patients hospitalized for mania (N = 66) were randomized after discharge to receive 24 weeks of adjunctive probiotics (Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or adjunctive placebo in a parallel two-group design format. The effect of treatment group on the risk of rehospitalization was calculated using Cox regression models. The modulating effect of systemic inflammation was measured employing an inflammation score based on immunoglobulin levels directed at previously defined antigens. RESULTS: During the 24-week observation period there were a total of 24 rehospitalizations in the 33 individuals who received placebo and eight rehospitalizations in the 33 individuals who received the probiotics (z = 2.63, P = .009). Hazard functions indicated that the administration of the probiotics was associated with a significant advantage in time to all psychiatric rehospitalizations (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.10, .69; P = .007). Probiotic treatment also resulted in fewer days rehospitalized (mean 8.3 vs 2.8 days for placebo and probiotic treatment, respectively; χ2  = 5.17, P = .017). The effect of the probiotic treatment on the prevention of rehospitalization was increased in individuals with elevated levels of systemic inflammation at baseline. CONCLUSION: Probiotic supplementation is associated with a lower rate of rehospitalization in patients who have been recently discharged following hospitalization for mania.

Clinical and Serological Predictors of Suicide in Schizophrenia and Major Mood Disorders.

Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study.

The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends towards improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms.

Individuals hospitalized with acute mania have increased exposure to antimicrobial medications.

OBJECTIVES: We have preciously documented that many individuals with acute mania have immune activation. However, the sources of immune activation have not been identified. We investigated whether individuals hospitalized with acute mania have evidence of bacterial infections as determined by the prescription of systemic antimicrobial agents. METHODS: We assessed the recent prescription of systemic antimicrobial medications and the site of presumed bacterial infection in 234 individuals hospitalized for acute mania in either an inpatient unit or a day hospital. We also assessed individuals hospitalized for other psychiatric disorders (n=368) and controls (n=555). We employed logistic regression models to compare the rates of antibiotic prescription in individuals with the different diagnoses, employing demographic variables as covariates. RESULTS: We found that individuals hospitalized with acute mania had a substantially increased rate of recent antimicrobial prescription, defined as exposure within three days of ascertainment (adjusted odds ratio=5.5, 95% confidence interval: 2.2-14.1, P<.0002). Overall, a total of 18 of the 234 (7.7%) individuals hospitalized for acute mania were prescribed antibiotics as opposed to seven of 555 (1.3%) controls. The prescription of antibiotics was associated with being on an inpatient unit as opposed to being in the day hospital, and having increased mania symptom severity but not with other clinical ratings, demographic variables, or psychiatric medications. Hospitalization for other psychiatric disorders was not associated with the recent prescription of antimicrobial medications. The urinary tract was the most common site of infection in women, while the respiratory tract and mucosal surfaces were the most common sites in men. CONCLUSIONS: Individuals hospitalized with acute mania have a markedly increased rate of bacterial infections, as evidenced by the recent prescription of antimicrobial agents. The prevention and effective treatment of bacterial infections may be important interventions for the management of individuals with mania.

Pentraxin 3 is reduced in bipolar disorder.

OBJECTIVE: Immunologic abnormalities have been found in bipolar disorder but pentraxin 3, a marker of innate immunity, has not been studied in this population. METHODS: Levels of pentraxin 3 were measured in individuals with bipolar disorder, schizophrenia, and non-psychiatric controls. Linear regression models were used to compare the pentraxin 3 levels in each of the psychiatric groups to that in the control group, adjusting for demographic and clinical variables. Logistic regression models were used to calculate the odds ratios associated with levels of pentraxin 3 which differed from specified levels of the control group. RESULTS: The sample consisted of 831 individuals: 256 with bipolar disorder, 309 with schizophrenia, and 266 without a psychiatric disorder. The levels of pentraxin 3 in the bipolar disorder, but not in the schizophrenia, group were significantly lower than those of controls, adjusting for age, gender, race, maternal education, smoking status, and body mass index (t = -3.78, p < 0.001). The individuals with bipolar disorder also had significantly increased odds of having low levels of pentraxin 3 relative to both the 10th and 25th percentile level of the controls and significantly decreased odds of having a level greater than the 75th and the 90th percentile level of the controls, adjusting for the same covariates. CONCLUSIONS: Individuals with bipolar disorder have low levels of pentraxin 3 which may reflect impaired innate immunity. An increased understanding of the role of innate immunity in the etiopathogenesis of bipolar disorder might lead to new modalities for the diagnosis and treatment of this 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.

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 and cognitive functioning in schizophrenia, bipolar disorder, and nonpsychiatric controls.

Increased rates of exposure to Toxoplasma gondii have been found in individuals with schizophrenia and bipolar disorder, but the association between Toxoplasma and cognitive functioning has not previously been examined. We measured IgG and IgM class antibodies to Toxoplasma in 408 nonelderly individuals with schizophrenia, 347 with bipolar disorder, and 352 nonpsychiatric controls. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status. Multivariate linear and regression analyses showed significant associations between Toxoplasma IgM antibody level and cognitive scores within the control group and the bipolar disorder group but not the schizophrenia group. Within the control group, having an elevated Toxoplasma IgM antibody level, greater than or equal to the 50th and 75th levels of the control group, was associated with significantly elevated odds of a low total cognitive score. Exposure to Toxoplasma may confer risk for lower cognitive functioning in persons without a psychiatric disorder and those with bipolar disorder.

Risk Factors for Natural Cause Mortality in Schizophrenia.

Importance: Schizophrenia is associated with premature mortality from mostly natural causes. Decreased cognitive functioning has been identified as a determinant of mortality in the general population. However, there have been few prospective studies of this issue in persons with schizophrenia. Objective: To examine whether lower cognitive functioning is a risk factor for natural cause mortality in schizophrenia. Design, Setting, and Participants: This prospective cohort study included persons with schizophrenia or schizoaffective disorder enrolled between February 1, 1999, and December 31, 2022, at a nonprofit psychiatric system in Baltimore, Maryland. Participants were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and other clinical measures. Exposure: Natural cause mortality. Main Outcomes and Measures: Associations of cognitive function, obesity, tobacco smoking, and medical conditions with natural cause mortality were evaluated using Cox proportional hazards regression models. Results: Of the 844 participants enrolled (mean [SD] age, 39.6 [12.1] years; 533 male [63.2%]), 158 (18.7%) died of natural causes during a median follow-up of 14.4 years (range, 7.0 days to 23.9 years). The most significant factor associated with mortality was lower cognitive functioning as measured by the RBANS (Cox coefficient, -0.04; 95% CI, -0.05 to -0.03; z = -5.72; adjusted P < .001). Additional factors independently associated with mortality included the diagnosis of an autoimmune disorder (hazard ratio [HR], 2.86; 95% CI, 1.83-4.47; z = 4.62; adjusted P < .001), tobacco smoking (HR, 2.26; 95% CI, 1.55-3.30; z = 4.23; adjusted P < .001), diagnosis of chronic obstructive pulmonary disease (HR, 3.31; 95% CI, 1.69-6.49; z = 3.48; adjusted P = .006), body mass index as a continuous variable (HR, 1.06; 95% CI, 1.02-1.09; z = 3.30; adjusted P = .01), diagnosis of a cardiac rhythm disorder (HR, 2.56; 95% CI, 1.40-4.69; z = 3.06; adjusted P = .02), and being divorced or separated (HR, 1.80; 95% CI, 1.22-2.65; z = 2.97; adjusted P = .02). An RBANS score below the 50th percentile displayed a joint association with being a smoker, having an elevated body mass index, and having a diagnosis of an autoimmune or a cardiac rhythm disorder. Conclusions and Relevance: In this prospective cohort study, lower cognitive functioning was a risk factor for natural cause mortality in schizophrenia. Efforts should be directed at methods to improve cognitive functioning, particularly among individuals with additional risk factors.

Anti-spike antibody responses to SARS-CoV-2 mRNA vaccines in people with schizophrenia and schizoaffective disorder.

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population. Objective: To assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder. Design: This cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine. Setting: A multi-center study including psychiatric healthcare settings in the United States and Europe. Participants: 205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021. Main outcomes and measures: Mean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination. Results: A total of 205 individuals (mean [SD] age, 44.7 [12.0] years; 90 [43.9%] male) were included, of which 106 (51.7%) were diagnosed with SZ. SZ was associated with lower mean log antibody levels (-0.15; 95% CI, -0.27 to -0.03, P = 0.016) after adjusting for age, sex, body mass index, smoking, days since vaccination, and vaccine manufacturer. In secondary analyses of dose-specific responses, SZ was associated with a lower mean log antibody level after the second dose of vaccine (-0.23; 95% CI -0.39 to -0.06, P = 0.006), but not the first dose of vaccine (0.00; 95% CI -0.18- 0.19, P = 0.96). Conclusions and Relevance: In this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia.

Cigarette smoking is associated with Herpesviruses in persons with and without serious mental illness.

INTRODUCTION: Herpesviruses are recognized as major causes of human diseases. Following initial infection, Herpesviruses can undergo cycles of reactivation controlled largely by the immune system. Cigarette smoking is an important modulator of the immune system particularly in individuals with serious mental illness where smoking is associated with increased rates of cardiopulmonary diseases and mortality. However, the effect of smoking on Herpesviruses has not been extensively studied. METHODS: In this nested cohort study, cigarette smoking was assessed in 1323 persons with serious mental illness or without a psychiatric disorder ascertained in a psychiatric health care system and the adjacent community. Participants provided a blood sample from which were measured IgG class antibodies to five human Herpesviruses: Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus-Type 1 (HSV-1); Varicella Zoster Virus (VZV); and Human Herpes Virus-Type 6 (HHV-6). The associations between smoking variables and antibody levels to the Herpesviruses were analyzed among diagnostic groups in multiple regression models adjusted for age, sex, and race. RESULTS: Current smoking was significantly associated with higher levels of antibodies to CMV (coefficient .183, 95% CI .049, .317, p<.001, q<.007) and the three EBV proteins (EBV NA -(coefficient .088, 95% CI .032, .143, p = .002, q<.014; EBV Virion - coefficient .100, 95% CI .037, .163, p = .002, q<.014; and EBV VCA - coefficient .119, 95% CI .061, .177, p = .00004, q<.0016). The amount of cigarettes smoked was also correlated with higher levels of antibodies to the three EBV proteins. Interaction analyses indicated that the association between cigarette smoking and levels of antibodies to CMV and EBV was independent of diagnostic group. Cigarette smoking was not significantly associated with the level of antibodies to HSV-1, VZV, or HHV-6. CONCLUSIONS: Individuals who smoke cigarettes have increased levels of IgG antibodies to CMV and EBV. Cigarette smoking may be a contributory factor in the relationship between CMV, EBV and chronic somatic disorders associated with these viruses.

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.

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.

Experiences of Persons With Serious Mental Illness During the COVID-19 Pandemic.

OBJECTIVE: This study aimed to characterize the experiences of persons with serious mental illness during the COVID-19 pandemic. METHODS: Adults with schizophrenia, bipolar disorder, major depression, or no psychiatric disorder (N=195) were interviewed between July 2020 and January 2021. All were previously enrolled in a cohort study. The interviews focused on mental distress and suicidal thoughts, the impact of the pandemic and pandemic-related worries, tobacco and alcohol use, and access to care. Responses of persons with serious mental illness were compared with responses of those without a psychiatric disorder by using multivariate ordered logistic regression analyses. For a subset of participants, responses about suicidal ideation were compared with their responses prior to the pandemic. RESULTS: Compared with participants with no psychiatric disorder, individuals with schizophrenia were more likely to endorse that they felt overwhelmed or anxious, had difficulty concentrating, or were concerned about medical bills and having enough food; they also reported significantly increased tobacco smoking. Individuals with bipolar disorder also reported more COVID-19-related worries than did participants without a psychiatric disorder. Overall, those with a psychiatric disorder reported more frequent mental distress and more recent missed medical visits and medications than did those with no psychiatric disorder. However, participants with serious mental illness did not report a higher rate of suicidal thoughts compared with their prepandemic responses. CONCLUSIONS: The pandemic poses significant challenges to individuals with serious mental illness in terms of COVID-19-related distress. Psychiatric services should proactively address the emotional distress and worries associated with the pandemic.

Markers of gluten sensitivity and celiac disease in bipolar disorder.

OBJECTIVES: Increased immune sensitivity to dietary gluten proteins has been reported in schizophrenia but has not been studied in bipolar disorder. In this study, we examine the levels of antibody reactivity to gliadin, deamidated gliadin, and tissue transglutaminase (tTG) in individuals with bipolar disorder and compare these levels to those in individuals who do not have any history of psychiatric disorder. METHODS: The sample of 275 individuals included 102 with bipolar disorder and 173 controls without a psychiatric disorder. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to gliadin and tTG and IgG antibodies to deamidated gliadin were measured by enzyme immunoassay. Participants' levels of antibodies to deamidated gliadin and tTG were classified based on the cutoffs for positivity that are predictive of celiac disease. Quantitative levels of antibodies were compared between groups employing regression models which were controlled for demographic variables. RESULTS: Individuals with bipolar disorder had increased levels of IgG antibodies to gliadin compared with controls in multivariate analyses. We also found evidence of increased levels of antibodies to deamidated gliadin in the bipolar disorder population. The levels of IgA class antigliadin antibodies and antibodies to tTG did not differ significantly between groups. There was also not a significant difference between groups in the number of persons who were classified as having levels of antibodies to deamidated gliadin or tTG that are predictive of celiac disease. CONCLUSIONS: Individuals with bipolar disorder have increased levels of IgG antibodies to gliadin. However, such antibody increase is not accompanied by an elevation in IgA antibodies to gliadin or the celiac disease-associated antibodies against deamidated gliadin and tTG. These results warrant further detailed examination of the molecular specificity and pattern of reactivity of the antibody response to gluten antigens in bipolar disorder.

Cognitive functioning in recent onset psychosis.

The purpose of the study was to compare the cognitive functioning of persons with a recent onset of psychosis with schizophrenia-spectrum disorders and bipolar disorder and nonpsychiatric controls. A total of 56 persons with a schizophrenia-spectrum disorder and 60 with bipolar disorder, all with a recent onset psychosis, and 312 nonpsychiatric controls were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Wisconsin Card Sorting Test (WCST). Comparison of the three groups through analysis of covariance indicated a significant difference among the groups for all of the cognitive variables. Pairwise contrasts of the two recent onset groups showed a significant difference favoring the bipolar disorder group on RBANS Language (p = 0.020) and Total (p = 0.050) and a marginally significant difference on RBANS Immediate Memory (p = 0.053) but not on the other RBANS variables or on the WCST. Cognitive performance is broadly impaired in recent onset psychosis, with a cognitive advantage to bipolar disorder patients compared with schizophrenia-spectrum patients.

Risk factors for natural cause mortality in a cohort of 1494 persons with serious mental illness.

Persons with serious mental illness die on average more than 10 years younger than those in the overall population, mostly due to natural causes. Previous studies have identified predictors of natural cause mortality in this population but few have been prospective studies using clinical variables from in-person evaluations. A cohort of 1494 individuals with schizophrenia, bipolar disorder, or major depressive disorder were assessed at baseline and mortality status was determined from the US National Death Index after up to 20 years of follow-up. Analyses included multivariate Cox proportional hazard models to determine independent predictors of natural cause mortality. A total of 125 (8.4%) individuals died of natural causes. In multivariate models, the strongest predictor of mortality after age was tobacco smoking at baseline with a dose-related effect. Having diabetes, a cardiovascular condition, particularly hypertension, and lower cognitive functioning were also significant risks, along with divorced/separated status. The receipt of gabapentin or fluoxetine also significantly increased mortality risk. Premature death can be reduced by smoking cessation and the improved management of conditions such as hypertension and diabetes.

Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia.

Cognitive deficits are a central feature of schizophrenia whose etiology is not fully understood. Epstein Barr Virus (EBV) is a potentially neurotropic infectious agent that can generate persistent infections with immunomodulatory effects. Previous studies have found an association between EBV antibodies and cognitive functioning in different populations, but there has been limited investigation in schizophrenia. In this study, 84 individuals with schizophrenia were administered a comprehensive neuropsychological battery, the MATRICS Consensus Cognitive Battery (MCCB). Participants also provided a blood sample, from which antibodies to the EBV whole virion and specific proteins were measured. Multivariate models were constructed to determine the association between these antibodies and cognitive performance on the MCCB overall and domain scores. Using these models, we found a significant association between the MCCB overall percent composite score and level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. A significant association was also found for the MCCB social cognition domain with the level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. In all cases, a higher level of antibodies was associated with a lower level cognitive performance. These findings suggest that exposure to EBV may contribute to cognitive deficits in schizophrenia, a finding which may have implications for new methods of prevention and treatment.

Occupational status and social adjustment six months after hospitalization early in the course of bipolar disorder: a prospective study.

OBJECTIVES: Bipolar disorder is often accompanied by poor functional outcomes, the determinants of which are not fully understood. We assessed patients with bipolar disorder undergoing a hospital admission early in the illness course and identified predictors of occupational status, overall social adjustment, and work adjustment six months later. METHODS: This was a prospective longitudinal cohort study. During hospitalization patients were evaluated with a cognitive battery; symptoms, occupational history, and other clinical factors were also assessed. At six-month follow-up, patients' symptom remission status was assessed; they were also evaluated as to their occupational status, overall social adjustment, and work adjustment. Multivariate analyses were used to identify predictors of these outcomes. RESULTS: Among the 52 participants, the average rating of overall social adjustment at follow-up was between mild and moderate maladjustment. While 51 had a history of working full time, only 28 (54%) worked full time at follow-up. A total of 24 (46%) had symptoms that met criteria for a full depression or mania syndrome. In multivariate analyses, full-time occupational status at follow-up was predicted by the absence of baseline substance abuse. Better overall social adjustment was predicted by better performance on cognitive tasks of processing speed and by symptom remission; the latter variable also predicted work adjustment. CONCLUSIONS: Persons with bipolar disorder have limited occupational recovery and overall social adjustment six months after a hospital admission early in the illness course. Predictors vary among outcomes; performance on tasks of processing speed and the extent of symptom remission are independently associated with functional outcomes.