Blunted ventral striatal reactivity to social reward is associated with more severe motivation and pleasure deficits in psychosis.

Among individuals living with psychotic disorders, social impairment is common, debilitating, and challenging to treat. While the roots of this impairment are undoubtedly complex, converging lines of evidence suggest that social motivation and pleasure (MAP) deficits play a key role. Yet most neuroimaging studies have focused on monetary rewards, precluding decisive inferences. Here we leveraged parallel social and monetary incentive delay fMRI paradigms to test whether blunted reactivity to social incentives in the ventral striatum-a key component of the distributed neural circuit mediating appetitive motivation and hedonic pleasure-is associated with more severe MAP symptoms in a transdiagnostic sample enriched for psychosis. To maximize ecological validity and translational relevance, we capitalized on naturalistic audiovisual clips of an established social partner expressing positive feedback. Although both paradigms robustly engaged the ventral striatum, only reactivity to social incentives was associated with clinician-rated MAP deficits. This association remained significant when controlling for other symptoms, binary diagnostic status, or ventral striatum reactivity to monetary incentives. Follow-up analyses suggested that this association predominantly reflects diminished striatal activation during the receipt of social reward. These observations provide a neurobiologically grounded framework for conceptualizing the social-anhedonia symptoms and social impairments that characterize many individuals living with psychotic disorders and underscore the need to establish targeted intervention strategies.

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.

Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein.

The PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length and G-C content play a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.

Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein.

The PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length plays a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.

Quantitative analyses of interactions between SpoVG and RNA/DNA.

The Borrelia burgdorferi SpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study were spoVG, glpFKD, erpAB, bb0242, flaB, and ospAB, with particular focus on the untranslated 5' portion of the mRNAs. Performing binding and competition assays yielded that the 5' end of spoVG mRNA had the highest affinity while the lowest observed affinity was to the 5' end of flaB mRNA. Mutagenesis studies of spoVG RNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation.

Quantitative analyses of interactions between SpoVG and RNA/DNA.

The Borrelia burgdorferi SpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study were spoVG, glpFKD, erpAB, bb0242, flaB, and ospAB, with particular focus on the untranslated 5' portion of the mRNAs. Performing binding and competition assays yielded that the 5' end of spoVG mRNA had the highest affinity while the lowest observed affinity was to the 5' end of flaB mRNA. Mutagenesis studies of spoVG RNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation.

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.

The Consistent Tick-Vertebrate Infectious Cycle of the Lyme Disease Spirochete Enables Borrelia burgdorferi To Control Protein Expression by Monitoring Its Physiological Status.

The Lyme disease spirochete, Borrelia burgdorferi, persists in nature by alternatingly cycling between ticks and vertebrates. During each stage of the infectious cycle, B. burgdorferi produces surface proteins that are necessary for interactions with the tick or vertebrate tissues it encounters while also repressing the synthesis of unnecessary proteins. Among these are the Erp surface proteins, which are produced during vertebrate infection for interactions with host plasmin, laminin, glycosaminoglycans, and components of the complement system. Erp proteins are not expressed during tick colonization but are induced when the tick begins to ingest blood from a vertebrate host, a time when the bacteria undergo rapid growth and division. Using the erp genes as a model of borrelial gene regulation, our research group has identified three novel DNA-binding proteins that interact with DNA to control erp transcription. At least two of those regulators are, in turn, affected by DnaA, the master regulator of chromosome replication. Our data indicate that B. burgdorferi has evolved to detect the change from slow to rapid replication during tick feeding as a signal to begin expression of Erp and other vertebrate-specific proteins. The majority of other known regulatory factors of B. burgdorferi also respond to metabolic cues. These observations lead to a model in which the Lyme spirochete recognizes unique environmental conditions encountered during the infectious cycle to "know" where they are and adapt accordingly.

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.

Sleep disturbance and sleep-related impairment in psychotic disorders are related to both positive and negative symptoms.

A large literature indicates that sleep disturbances are associated with paranoia and other positive symptoms in psychotic disorders. However, few studies have examined the potential association between sleep disturbances and negative symptoms and the results have been inconsistent. The current study examined the hypothesis that sleep problems would be associated with more severe positive and negative symptoms in a transdiagnostic sample of individuals with psychosis (N = 90). Further, we examined whether sleep would be related to negative symptoms above and beyond the contribution of paranoia, other positive symptoms, and depression-anxiety. Results replicated prior research in finding that both sleep disturbance and sleep-related impairment were related to more severe paranoia, other positive symptoms and depression-anxiety. Consistent with our hypothesis, more severe sleep disturbance and sleep-related impairment were related to greater negative symptoms; this was evident across both motivation-pleasure deficits and diminished expression. Sleep variables remained significantly related to motivation-pleasure deficits even after controlling for other non-negative symptoms. These results indicate the broad symptom impact of sleep disturbances and may suggest a novel treatment target to improve negative symptoms.

The Lyme disease spirochete's BpuR DNA/RNA-binding protein is differentially expressed during the mammal-tick infectious cycle, which affects translation of the SodA superoxide dismutase.

When the Lyme disease spirochete, Borrelia burgdorferi, transfers from a feeding tick into a human or other vertebrate host, the bacterium produces vertebrate-specific proteins and represses factors needed for arthropod colonization. Previous studies determined that the B. burgdorferi BpuR protein binds to its own mRNA and autoregulates its translation, and also serves as co-repressor of erp transcription. Here, we demonstrate that B. burgdorferi controls transcription of bpuR, expressing high levels of bpuR during tick colonization but significantly less during mammalian infection. The master regulator of chromosomal replication, DnaA, was found to bind specifically to a DNA sequence that overlaps the bpuR promoter. Cultured B. burgdorferi that were genetically manipulated to produce elevated levels of BpuR exhibited altered levels of several proteins, although BpuR did not impact mRNA levels. Among these was the SodA superoxide dismutase, which is essential for mammalian infection. BpuR bound to sodA mRNA in live B. burgdorferi, and a specific BpuR-binding site was mapped 5' of the sodA open reading frame. Recognition of posttranscriptional regulation of protein levels by BpuR adds another layer to our understanding of the B. burgdorferi regulome, and provides further evidence that bacterial protein levels do not always correlate directly with mRNA levels.

Transcriptomic insights on the virulence-controlling CsrA, BadR, RpoN, and RpoS regulatory networks in the Lyme disease spirochete.

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical regulatory proteins were examined in a uniform strain background. Pairs of mutants and their wild-type parent were grown simultaneously under a single, specific culture condition, permitting direct comparisons between the mutant strains. Transcriptomic analyses were strand-specific, and assayed both coding and noncoding RNAs. Intersection analyses identified regulatory overlaps between regulons, including transcripts involved in carbohydrate and polyamine metabolism. In addition, it was found that transcriptional units such as ospC and dbpBA, which were previously observed to be affected by alternative sigma factors, are transcribed by RNA polymerase using the housekeeping sigma factor, RpoD.

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.

Borrelia burgdorferi SpoVG DNA- and RNA-Binding Protein Modulates the Physiology of the Lyme Disease Spirochete.

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations.IMPORTANCEB. burgdorferi persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that B. burgdorferi controls production of SpoVG and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression of spoVG exerts effects on bacterial replication and other aspects of the spirochete's physiology.

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.

Cigarette Smoking by Patients With Serious Mental Illness, 1999-2016: An Increasing Disparity.

OBJECTIVE: This study examined the prevalence of cigarette smoking and the quantity of cigarettes consumed by individuals with schizophrenia and bipolar disorder and those without a psychiatric disorder in the period 1999-2016. METHOD: A total of 1,938 individuals provided information about their cigarette smoking at enrollment into a research study for which they were selected without regard to their smoking status. Differences among groups and trends over time in smoking and cigarette consumption were examined by using multivariate models. RESULTS: Marked differences between groups were noted in the prevalence of smoking and in the quantity of cigarettes consumed. Overall, 62% of individuals with schizophrenia, 37% with bipolar disorder, and 17% of participants without a psychiatric disorder (control group) reported that they were current smokers. Smoking prevalence decreased over time in the sample primarily because of the decrease in smoking in the control group. Smokers with schizophrenia and with bipolar disorder smoked more cigarettes per day than smokers in the control group. Among smokers in all the groups, the quantity of cigarettes consumed per day declined significantly over the study period. Smoking was significantly associated with older age, less education, Caucasian race, and male gender. CONCLUSIONS: The prevalence of smoking has remained alarmingly high among individuals with schizophrenia and bipolar disorder, and the disparity with those without psychiatric disorders and with the general population is increasing. Additional measures are urgently needed to address this major public health problem.

The association between immune markers and recent suicide attempts in patients with serious mental illness: A pilot study.

Previous studies have identified elevations in markers of gastrointestinal inflammation in schizophrenia and mood disorders but studies have not measured the association between these markers and recent suicide attempts. We assessed 210 patients receiving treatment for schizophrenia, bipolar disorder, or major depression. We employed the Columbia Suicide Severity Rating Scale to identify recent and lifetime suicide attempts (actual, aborted, and interrupted). Psychiatric participants and a control group of 72 individuals without a psychiatric disorder had a blood sample drawn from which were measured specific markers of gastrointestinal inflammation and also C-Reactive protein (CRP). A total of 20 (10%) of psychiatric participants had a suicide attempt in the previous one month and 95 (45%) an attempt during their lifetime but not in the previous one month. The recent attempters had significantly elevated levels of antibodies to yeast mannan from Saccharomyces cerevisiae (ASCA), the food antigen gliadin, and bacterial lipopolysaccharide (LPS) compared with the non-psychiatric group when adjusting for demographic and clinical variables. These markers were not elevated in individuals with a past, but not recent, suicide attempt history. Our study indicates that there is evidence of gastrointestinal inflammation in some individuals who have had a recent suicide attempt.