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.

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.

Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder.

Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C.

Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder.

Objectives: Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder.

Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.

The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies.

Cigarette smoking among persons with schizophrenia or bipolar disorder in routine clinical settings, 1999-2011.

Objective: This study examined the prevalence of cigarette smoking and the quantity of cigarettes consumed by individuals with schizophrenia or bipolar disorder and by those with no psychiatric disorder in the period 1999-2011.

Methods: A total of 991 individuals with schizophrenia, bipolar disorder, or no psychiatric illness provided information about their cigarette smoking at recruitment into a research study for which they were selected without regard to their smoking status. Differences among groups and trends over time among new enrollees were examined with multivariate models.

Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia.

Immune system factors including complement pathway activation are increasingly linked to the etiology and pathophysiology of schizophrenia. Complement protein, C1q, binds to and helps to clear immune complexes composed of immunoglobulins coupled to antigens. The antigenic stimuli for C1q activation in schizophrenia are not known.

Gastrointestinal inflammation and associated immune activation in schizophrenia.

Immune factors are implicated in normal brain development and in brain disorder pathogenesis. Pathogen infection and food antigen penetration across gastrointestinal barriers are means by which environmental factors might affect immune-related neurodevelopment. Here, we test if gastrointestinal inflammation is associated with schizophrenia and therefore, might contribute to bloodstream entry of potentially neurotropic milk and gluten exorphins and/or immune activation by food antigens.

Dietary antigens, epitope recognition, and immune complex formation in recent onset psychosis and long-term schizophrenia.

Peptides derived from dietary antigens such as bovine milk caseins are opioid receptor ligands and contribute to schizophrenia-associated hyperpeptidemia and hyperpeptiduria. The IgG antibody response to bovine caseins is increased in schizophrenia and recent onset psychosis. To identify specific casein peptide sequences that are antigenic in patients vs controls, we measured serum IgG binding to 10-26 amino acid long linear epitopes of casein with immunoassays for the entire group (n=95 recent onset psychosis; n=103 long-term schizophrenia; n=65 control), and with peptide microarray libraries in a casein-sensitive subset (n=14 recent onset; n=10 control).

Immune activation by casein dietary antigens in bipolar disorder.

Objectives:   Inflammation and other immune processes are increasingly linked to psychiatric diseases. Antigenic triggers specific to bipolar disorder are not yet defined. We tested whether antibodies to bovine milk caseins were associated with bipolar disorder, and whether patients recognized different epitopes of the casein protein than control individuals.

Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia.

Previous studies show increased antibody levels to bovine casein in some individuals with schizophrenia. The immunogenicity of specific domains of bovine casein varies among people with milk sensitivities and thus could vary among different neuropsychiatric disorders. Using ELISAs and immunoblotting, we characterized IgG class antibody specificity to whole bovine casein and to the alpha(s), beta, and kappa subunits in individuals with recent onset psychosis (n=95), long-term schizophrenia (n=103), and non-psychiatric controls (n=65).

Coronavirus immunoreactivity in individuals with a recent onset of psychotic symptoms.

Prenatal influenza exposure increases the risk for schizophrenia and brings to question how other respiratory viruses may contribute to neuropsychiatric disease etiopathology. Human coronaviruses cause respiratory infections that range in seriousness from common colds to severe acute respiratory syndrome. Like influenza, coronaviruses can be neurotropic.

A double-blind trial of adjunctive allopurinol for schizophrenia.

Objective: To investigate if adjunctive allopurinol reduces symptoms in schizophrenia outpatients with persistent symptoms despite adequate pharmacotherapy.

Method: N=59 schizophrenia outpatients were randomly assigned to receive adjunctive allopurinol 300 mg bid or identical-looking placebo for 8 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly.

Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.

Nicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)].

Double blind trial of adjunctive valacyclovir in individuals with schizophrenia who are seropositive for cytomegalovirus.

Objective: To investigate if adjunctive valacyclovir, an antiviral medication, reduces symptoms of persistent schizophrenia in individuals who are seropositive for cytomegalovirus (CMV).

Method: N=47 CMV seropositive schizophrenia outpatients were randomly assigned to receive valacyclovir 1 g twice daily (n=24) or placebo (n=23) for 16 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly.

Development of a nucleocapsid-based human coronavirus immunoassay and estimates of individuals exposed to coronavirus in a U.S. metropolitan population.

Coronaviruses cause respiratory infections ranging from common colds to severe acute respiratory syndrome (SARS) in humans. Estimates for exposure to non-SARS coronaviruses are high, particularly for 229E and OC43; however, less information regarding seroprevalence is available for HKU1 and NL63. To measure exposure rates to these four coronavirus strains (229E, HKU1, NL63, and OC43), we devised an immunoassay based on amino- and carboxy-terminally tagged recombinant coronavirus nucleocapsid antigens.

The catechol O-methyltransferase Val158Met polymorphism is not associated with broad-based cognitive functioning in schizophrenia.

Background: A valine/methionine polymorphism of the catechol O-methyltransferase gene at the nucleotide which encodes amino acid val or met at position 158 in the protein (COMT Val158Met polymorphism) has been associated with deficits in executive functioning in schizophrenia in some studies. The association between the COMT polymorphism and other cognitive domains has been the focus of only limited investigation.

Methods: We measured COMT Val158Met genotypes in N=364 individuals with schizophrenia.

The catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection are risk factors for cognitive impairment in bipolar disorder: additive gene-environmental effects in a complex human psychiatric disorder.

Background: Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia.

Cognitive functioning in schizophrenia and bipolar disorder: comparison of performance on the Repeatable Battery for the Assessment of Neuropsychological Status.

Cognitive dysfunction is an important feature of schizophrenia and bipolar disorder. There is uncertainty about the relative magnitude of cognitive deficits in these disorders. We evaluated a total of 446 individuals: 229 with schizophrenia, 117 with bipolar disorder, and 100 controls without a history of psychiatric disorder.

Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder.

Background: In a previous investigation, we found an association between reduced cognitive functioning and the prevalence of antibodies to herpes simplex virus type 1 in individuals with schizophrenia. The current study was undertaken to determine if this association also occurs in individuals with bipolar disorder.

Methods: Cognitive functioning and serologic evidence of infection with potentially neurotropic herpesviruses were measured in 117 individuals with bipolar disorder and in 100 individuals without a history of psychiatric disorder.

Association between cognitive functioning and employment status of persons with bipolar disorder.

Objective: The purpose of this study was to identify variables associated with employment status among persons with bipolar disorder, including cognitive functioning, severity of symptoms, demographic variables, and variables related to course of illness.

Methods: The authors assessed the current employment status of 117 persons with bipolar disorder. Study participants' cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status, the information and letter-number sequencing subtests of the Wechsler Adult Intelligence Scale III, and part A of the Trail Making Test.

Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia.

Objective: The study was an investigation of the effect of the antiviral medication valacyclovir on the symptoms of outpatients with persistent schizophrenia.

Method: Oral valacyclovir, 1 g twice daily, was administered to 65 outpatients over 16 weeks along with their usual psychiatric medications. Changes in psychiatric symptoms were measured with the Positive and Negative Syndrome Scale and were tested for correlations with antibodies to potentially neurotropic human herpesviruses, as measured by immunoassay before the start of the therapy.

Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia.

Background: Cognitive deficits are a characteristic feature of schizophrenia and contribute to the profound disabilities associated with this illness. Some of the cognitive deficits that occur in individuals with schizophrenia are similar to those found in individuals who have recovered from central nervous system infections with human herpesviruses.

Methods: We measured cognitive functioning and serologic evidence of infection with human herpesviruses in 229 outpatients with schizophrenia.

An expanded version of the Multnomah Community Ability Scale: anchors and interview probes for the assessment of adults with serious mental illness.

Objective clinical assessments are important in psychiatric settings to assess patients' functioning and the outcome of rehabilitation interventions. We developed anchors of the Multnomah Community Ability Scale (MCAS) and tested the inter-rater reliability of the expanded instrument. Twenty patients receiving psychiatric rehabilitation services participated in a structured interview and were rated by two raters.