The impact of the COVID-19 pandemic on perceptions of social relationships, negative affect, and paranoid ideation.

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.

Understanding the Consequences of Moment-by-Moment Fluctuations in Mood and Social Experience for Paranoid Ideation in Psychotic Disorders.

Among individuals with psychotic disorders, paranoid ideation is common and associated with increased impairment, decreased quality of life, and a more pessimistic prognosis. Although accumulating research indicates negative affect is a key precipitant of paranoid ideation, the possible protective role of positive affect has not been examined. Further, despite the interpersonal nature of paranoid ideation, there are limited and inconsistent findings regarding how social context, perceptions, and motivation influence paranoid ideation in real-world contexts. In this pilot study, we used smartphone ecological momentary assessment to understand the relevance of hour-by-hour fluctuations in mood and social experience for paranoid ideation in adults with psychotic disorders. Multilevel modeling results indicated that greater negative affect is associated with higher concurrent levels of paranoid ideation and that it is marginally related to elevated levels of future paranoid ideation. In contrast, positive affect was unrelated to momentary experiences of paranoid ideation. More severe momentary paranoid ideation was also associated with an elevated desire to withdraw from social encounters, irrespective of when with familiar or unfamiliar others. These observations underscore the role of negative affect in promoting paranoid ideation and highlight the contribution of paranoid ideation to the motivation to socially withdraw in psychotic disorders.

Assessing the psychometric properties of the PROMIS sleep measures in persons with psychosis.

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.

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.

A Randomized Clinical Trial of Oxytocin or Galantamine in Schizophrenia: Assessing the Impact on Behavioral, Lexical, and Self-Report Indicators of Social Affiliation.

Prior studies examining the impact of oxytocin on negative symptoms in schizophrenia have yielded mixed results. The current study explored whether oxytocin can improve more proximal indicators of social affiliation as indicated by changes in behavior, language and subjective indices of social affiliation among individuals with schizophrenia spectrum disorders during a role-play designed to elicit affiliative responses. We tested the hypothesis that daily intranasal oxytocin administered for 6 weeks would improve social affiliation as manifested by increased social skill ratings, use of positive, affiliative, and social words, and subjective responses from a previously published randomized controlled trial. Forty outpatients with schizophrenia or schizoaffective disorder were randomized to the oxytocin, galantamine, or placebo group and completed affiliative role-plays and self-report questionnaires of affect, reactions to the affiliative confederate, and willingness to interact at baseline and post-treatment. Results demonstrated that oxytocin was not effective at improving behavioral or subjective indicators of social affiliation. This study adds to a growing literature that the prosocial effects of oxytocin in schizophrenia are limited or null.

Sleep Problems and Social Impairment in Psychosis: A Transdiagnostic Study Examining Multiple Social Domains.

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.

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.

The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls.

Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV-1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was -0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning.

Mortality in schizophrenia and bipolar disorder: Clinical and serological predictors.

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 14years. 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.

The Experience of Peer Mentors in an Intervention to Promote Smoking Cessation in Persons with Psychiatric Illness.

Peer support is an important component of services for persons with psychiatric illness but the experience of peer mentors is not well understood. This study explored the experiences of peer mentors, all former smokers and persons with psychiatric illness, who provided smoking cessation counseling as part of a 6 month professionally-led intervention. Data was obtained from 383 contact log entries and in-depth interviews with eight peer mentors. Qualitative analysis indicated that mentor roles were unexpectedly varied beyond the focus on smoking cessation. Of the two aspects of "peer-ness," shared smoking history was more prominent, while the shared experience of psychiatric illness was sometimes overlooked. Peer mentors experienced multiple challenges trying to help participants to change their smoking behaviors. Nonetheless, they described their experience as personally rewarding. Future interventions may be improved by anticipating peer mentor role complexity and the inherent tension between providing person-centered support and promoting behavior change.

The use of peer mentors to enhance a smoking cessation intervention for persons with serious mental illnesses.

OBJECTIVE: We evaluated a well-specified peer mentor program that enhanced a professionally led smoking cessation group for persons with serious mental illnesses. METHOD: Participants were 8 peer mentors, persons with serious mental illnesses who had successfully quit smoking, and 30 program participants, persons with serious mental illnesses enrolled in a 6-month intervention. Peer mentors were trained and then helped to deliver a smoking cessation group and met with program participants individually. We assessed the mentors' skills after training, their fidelity to the model, and the program's feasibility and acceptability. We also measured the smoking outcomes of the program participants including change in exhaled carbon monoxide, a measure of recent smoking, and aspects of the peer mentor-program participant relationship. RESULTS: Peer mentors attained a mean score of 13.6/14 on role play assessments after training and delivered the intervention with fidelity as assessed by adherence and competence ratings (mean scores of 97% and 93%, respectively). The feasibility and acceptability of the intervention was demonstrated in that 28/30 participants met with their peer mentors regularly and only 1 participant and no peer mentor discontinued in the study. Both parties rated the interpersonal alliance highly, mean of 5.9/7. The program participants had a decline in carbon monoxide levels and number of cigarettes smoked per day (repeated measures ANOVA F = 6.04, p = .008; F = 15.87, p < .001, respectively). A total of 22/30 (73%) made a quit attempt but only 3 (10%) achieved sustained abstinence. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our study adds to the growing literature about peer-delivered interventions.

Metagenomic Sequencing Indicates That the Oropharyngeal Phageome of Individuals With Schizophrenia Differs From That of Controls.

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.

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.

Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01242371.

A longitudinal study of cognitive functioning in schizophrenia: clinical and biological predictors.

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.

Association between cytomegalovirus antibody levels and cognitive functioning in non-elderly adults.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.