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.

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.

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.