Highlights • In schizophrenia, elevated Candida yeast antibody levels were lowered by probiotics. • Probiotics compared to placebo also relieved yeast-related bowel discomfort over time. • Candida ...albicans seropositivity was associated with worse psychiatric symptoms.
Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive ...functioning in younger adults has not been established.
We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group.
Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient -1.03, p<.0002), Delayed Memory (coefficient -0.94, p<.001), Visuospatial/Constructional (coefficient -1.77, p<5×10(-7)), and Letter Number Sequencing (coefficient -0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045), 2.22 (95th % CI 1.33, 3.70; p<.002), and 2.46 (95th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively.
Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an improvement in cognitive functioning in otherwise healthy adults.
Mucosal sites such as the oropharynx contain a wide range of microorganisms, collectively designated as the microbiome. The microbiome can affect behavior through a number of neurobiological and ...immunological mechanisms. Most previous studies have focused on the bacterial components of the microbiome. However, the microbiome also includes viruses such as bacteriophages, which are viruses that infect bacteria and alter their metabolism and replication. We employed metagenomic analysis to characterize bacteriophage genomes in the oral pharynx of 41 individuals with schizophrenia and 33 control individuals without a psychiatric disorder. This analysis was performed by the generation of more than 100,000,000 sequence reads from each sample and the mapping of these reads to databases. We identified 79 distinct bacteriophage sequences in the oropharyngeal samples. Of these, one bacteriophage genome, Lactobacillus phage phiadh, was found to be significantly different in individuals with schizophrenia (P < .00037, q < 0.03 adjusted for multiple comparisons). The differential levels of Lactobacillus phage phiadh remained significant when controlling for age, gender, race, socioeconomic status, or cigarette smoking (P < .006). Within the group of individuals with schizophrenia, the level of Lactobacillus phage phiadh correlated with the prevalence of immunological disorders as well as with the administration of valproate, which has been shown in animal models to alter the microbiome. The bacteriophage composition of the oropharynx in individuals with schizophrenia differs from that of controls. The biological consequences of this difference and the potential effects of altering bacteriophage levels through therapeutic interventions are worthy of further investigation.
Abstract
An accumulation of research has indicated that persons with psychotic disorders experience a variety of sleep disturbances. However, few studies have examined the psychometric properties of ...sleep assessments that are utilized in this population. We conducted two studies to examine the reliability and validity of the PROMISTM Sleep Disturbance and Sleep-Related Impairment scales in outpatient samples of persons with psychosis. In Study 1, we examined the internal consistency and convergent validity of the PROMIS sleep scales in individuals with various psychotic disorders (N = 98) and healthy controls (N = 22). The PROMIS sleep scales showed acceptable internal consistency and convergent validity in both healthy controls and individuals with psychotic disorders. In addition, replicating prior research, the PROMIS scales identified greater sleep disturbance and sleep-related impairment in participants with psychotic disorders compared to healthy controls. In Study 2, we examined the test-retest reliability (M = 358 days) of the PROMIS sleep scales in a subset (N = 37) of persons with psychotic disorders who previously participated in Study 1. We also assessed the relation between these self-report measures and actigraph sleep parameters. The results showed that PROMIS sleep measures demonstrated modest temporal stability in the current sample. Contrary to our hypothesis, there was a lack of correspondence between these scales and actigraph sleep parameters. Overall, these findings indicate that the PROMIS sleep scales are psychometrically sound measures for populations with psychosis and highlight the importance of utilizing a multi-method approach to assess sleep.
The COVID-19 pandemic contributed to worsening mental health across the globe. The pandemic may have been especially impactful on those experiencing heightened psychosis spectrum symptomatology given ...greater pre-pandemic social isolation and increased vulnerability to stress. Yet, few studies exploring the impact of the COVID-19 pandemic on perceptions of social relationships and mental health have sampled individuals high in psychosis spectrum symptomatology, including those with psychosis spectrum disorders. Utilizing a mixed transdiagnostic community sample enriched for psychotic spectrum disorders, this longitudinal study investigated whether perceptions of social relationships and psychiatric symptoms changed during the COVID-19 pandemic, whether pandemic-related impacts were associated with social perceptions and symptomatology, and whether paranoid ideation was related to perceptions of the government response to the COVID-19 pandemic. Pandemic impacts were not uniform, with participants reporting a range of adverse impacts including poorer health-related behaviors, difficulties fulfilling basic needs, and medical related challenges. Results indicated that compared to pre-pandemic assessments, perceived rejection and hostility increased during the COVID-19 pandemic. Participants who experienced more pandemic-related impacts reported less social support, more social distress, greater negative affect, and greater paranoid ideation. Paranoid ideation was related to more negative perceptions of the government's response to the pandemic. These findings demonstrate the importance of assessing individual differences in pandemic-related impacts and the clinical consequences of such impacts. Results also suggest that those high in paranoid ideation may be reluctant to engage in government recommended protective health behaviors to limit the spread of COVID-19.
Abstract Background Cognitive deficits are a central feature of schizophrenia but it is not certain how cognitive functioning changes over time. The purpose of this prospective longitudinal study was ...to determine the temporal change of cognitive functioning and the predictors of cognitive performance from among demographic, clinical, and biological variables. Methods Participants were individuals with schizophrenia or schizoaffective disorder whose cognitive functioning was assessed at multiple time points with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). At the baseline visit participants had a blood sample drawn from which C-reactive protein, antibodies to Herpes Simplex Virus type 1, and selected genetic polymorphisms were measured. Repeated measures linear regression was used to determine whether cognitive measures changed over time and which variables predicted cognitive performance. Results The sample consisted of 132 participants, mean age 43.7 years at baseline, who received a median of 3 cognitive assessments over a period averaging 2.8 years. The RBANS Total score and Language index showed no statistically significant temporal change; performance on two indices, Immediate Memory and Attention, showed modest but statistically significant improvements (gains of 0.89 ± 0.33 and 0.76 ± 0.29 points per year, respectively); Visuospatial/Constructional performance showed a modest but statistically significant decline (of 0.80 ± 0.25 points per year). Few variables predicted cognitive performance; however greater psychiatric symptom severity was associated with worse cognitive performance for most cognitive measures. Conclusions Cognitive functioning in middle-aged persons with schizophrenia showed an absence of decline for most measures and modest gains in some measures.
Psychotic disorders are characterized by profound social impairment. An accumulation of research has explored the contribution of symptoms, cognitive functioning, and behavioral skills deficits to ...this social dysfunction. Recent research indicates that sleep disturbance has significant social implications in nonclinical populations-this research suggests that sleep problems may also be relevant to understanding social impairment in psychosis. This study adopted a symptom-oriented dimensional approach to examine how sleep disturbance and sleep-related impairment are related to multiple social domains within a transdiagnostic sample (N = 90). This sample included individuals with a variety of psychotic disorders (n = 75) along with healthy non-clinical participants (n = 15) to ensure sampling across the full range of sleep problems and social functioning. Social domains spanned self-reported perceptions of social relationships, social functioning in the community, and behavioral assessments of social competence. We hypothesized that greater sleep disturbance and sleep-related impairment would be associated with more negative or problematic perceptions of social relationships (i.e., less social support, less companionship, and greater distress), poorer social functioning in the community, smaller social networks, and poorer behavioral ratings of social competency. Results supported these hypotheses indicating that sleep disturbance and sleep-related impairment have widespread deleterious impacts on perceptions of social relationships, social functioning, and competence. Sleep disturbance retained associations with perceptions of social relationships, social functioning, and social competence even after controlling for total symptoms or cognitive functioning. These findings indicate that sleep problems may have important implications for fully understanding the causes of social impairment in psychosis.
A range of immune system abnormalities have been associated with schizophrenia. Probiotic compounds modulate the immune response and offer a potential treatment strategy for schizophrenia. Probiotic ...compounds have also been observed to improve gastrointestinal dysfunction, which is a common problem in individuals with schizophrenia. We performed a randomized, double-blind, placebo-controlled trial to examine whether probiotic supplementation can reduce symptom severity in patients with schizophrenia receiving antipsychotic treatment and also whether probiotics are associated with bowel functioning.
Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least moderately severe psychotic symptoms were enrolled in the study from December 2010-August 2012. Following a 2-week placebo run-in period, patients were randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with the Positive and Negative Syndrome Scale (PANSS), and patients were queried weekly about their gastrointestinal functioning.
Repeated-measures analysis of variance showed no significant differences in the PANSS total score between probiotic and placebo supplementation (F = 1.28, P = .25). However, patients in the probiotic group were less likely to develop severe bowel difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09-0.61, P = .003).
Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia.
ClinicalTrials.gov identifier: NCT01242371.
Abstract Persons with schizophrenia and with bipolar disorder have a reduced life expectancy due largely to death from natural causes. The reasons for this increased mortality have not been ...completely defined. We prospectively assessed a cohort of persons with schizophrenia and one with bipolar disorder with a clinical evaluation and a blood sample from which immune and infectious disease markers were measured. Mortality was determined with data from the National Death Index following a period of up to 14 years. We examined the role of demographic, clinical, and serological factors on mortality in bivariate and multivariate models. A total of 43/710 (6.1%) persons with schizophrenia and 12/406 (3.0%) with bipolar disorder died of natural causes. In the schizophrenia group, mortality was predicted by the following variables in a multivariate model: cigarette smoking (RR = 6.93, 95% CI 1.59, 30.1, p = 0.0099); autoimmune disorder (RR = 8.08, 95% CI 2.50, 26.1, p = 0.00047); gastrointestinal disorder (GI) (RR = 3.53, 95% CI 1.43, 8.69 p = 0.0061); and reduced maternal education (RR = 0.84, 95% CI 0.72, 0.97), p = 0.018. The combination of smoking and an autoimmune disorder yielded an unadjusted relative risk of 18.1 for mortality, and the combination of smoking and a GI disorder an unadjusted relative risk of 9.45, compared with individuals with neither risk factor. In the bipolar disorder group, significant bivariate predictors of mortality included lower cognitive score (RR = 0.95, p = .0085) and the presence of type 1 or 2 diabetes (RR = 3.90, p = .026). Given the extraordinary high risk of death due to smoking in schizophrenia, smoking cessation remains an urgent priority.
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.
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