Effect of a Tobacco Cessation Intervention Incorporating Weight Management for Adults With Serious Mental Illness: A Randomized Clinical Trial.

Importance: Tobacco smoking drives markedly elevated cardiovascular disease risk and preventable death in persons with serious mental illness, and these risks are compounded by the high prevalence of overweight/obesity that smoking cessation can exacerbate. Guideline-concordant combined pharmacotherapy and behavioral smoking cessation treatment improves abstinence but is not routinely offered in community settings, particularly to those not seeking to quit smoking immediately. Objective: To determine the effectiveness of an 18-month pharmacotherapy and behavioral smoking cessation intervention incorporating weight management and support for physical activity in adults with serious mental illness interested in quitting smoking within 1 or 6 months. Design, Setting, and Participants: This was a randomized clinical trial conducted from July 25, 2016, to March 20, 2020, at 4 community health programs. Adults with serious mental illness who smoked tobacco daily were included in the study. Participants were randomly assigned to intervention or control, stratified by willingness to try to quit immediately (within 1 month) or within 6 months. Assessors were masked to group assignment. Interventions: Pharmacotherapy, primarily varenicline, dual-form nicotine replacement, or their combination; tailored individual and group counseling for motivational enhancement; smoking cessation and relapse prevention; weight management counseling; and support for physical activity. Controls received quitline referrals. Main Outcome and Measures: The primary outcome was biochemically validated, 7-day point-prevalence tobacco abstinence at 18 months. Results: Of the 298 individuals screened for study inclusion, 192 enrolled (mean [SD] age, 49.6 [11.7] years; 97 women [50.5%]) and were randomly assigned to intervention (97 [50.5%]) or control (95 [49.5%]) groups. Participants self-identified with the following race and ethnicity categories: 93 Black or African American (48.4%), 6 Hispanic or Latino (3.1%), 90 White (46.9%), and 9 other (4.7%). A total of 82 participants (42.7%) had a schizophrenia spectrum disorder, 62 (32.3%) had bipolar disorder, and 48 (25.0%) had major depressive disorder; 119 participants (62%) reported interest in quitting immediately (within 1 month). Primary outcome data were collected in 183 participants (95.3%). At 18 months, 26.4% of participants (observed count, 27 of 97 [27.8%]) in the intervention group and 5.7% of participants (observed count, 6 of 95 [6.3%]) in the control group achieved abstinence (adjusted odds ratio [OR], 5.9; 95% CI, 2.3-15.4; P < .001). Readiness to quit within 1 month did not statistically significantly modify the intervention's effect on abstinence. The intervention group did not have significantly greater weight gain than the control group (mean weight change difference, 1.6 kg; 95% CI, -1.5 to 4.7 kg). Conclusions and Relevance: Findings of this randomized clinical trial showed that in persons with serious mental illness who are interested in quitting smoking within 6 months, an 18-month intervention with first-line pharmacotherapy and tailored behavioral support for smoking cessation and weight management increased tobacco abstinence without significant weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT02424188.

Non-SARS Coronaviruses in Individuals with Psychiatric Disorders.

BACKGROUND: The pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has highlighted the importance of coronaviruses in human health. Several seasonal, non-SARS Coronaviruses are endemic in most areas of the world. In a previous study, we found that the level of antibodies to these seasonal Coronaviruses was elevated in persons with a recent onset of psychosis. In the current study, the level of antibodies to seasonal Coronaviruses was compared between individuals with psychiatric disorders and a non-psychiatric comparison group. METHODS: Participants (N = 195) were persons with a diagnosis of schizophrenia, bipolar disorder, major depressive disorder, or without a psychiatric disorder. Each participant had a blood sample drawn from which were measured IgG antibodies to the spike proteins in four non-SARS Coronaviruses, 229E, HKU1, NL63, and OC43, using a multiplex electrochemiluminescence assay. Linear regression models were employed to compare the levels of antibodies between each psychiatric group and the comparison group adjusting for demographic variables. Logistic regression models were employed to calculate the odds ratios associated with increased levels of antibodies to each seasonal Coronavirus based on the 50th percentile level of the comparison group. RESULTS: The schizophrenia group had significantly increased levels of antibodies to the seasonal Coronaviruses OC43 and NL63. This group also had increased odds of having elevated antibody levels to OC43. The major depression group showed a significantly lower level of antibodies to Coronavirus 229E. There were no significant differences between any of the psychiatric groups and the comparison group in the levels of antibodies to seasonal Coronaviruses 229E or HKU1. CONCLUSIONS: The elevated level of antibodies to OC43 and NL63 in the schizophrenia group indicates increased exposure to these agents and raises the possibility that Coronaviruses may contribute to the etiopathology of this disorder. The cause-and-effect relationship between seasonal Coronaviruses and psychiatric disorders should be the subject of additional investigations focusing on longitudinal cohort studies.

Physical Activity Levels and Screen Time among Youth with Overweight/Obesity Using Mental Health Services.

Youth with mental illness have higher levels of obesity than children in the general population. Both regular physical activity and limited screen time have been recommended to reduce and prevent childhood obesity. This study examines accelerometer-based moderate-vigorous physical activity (MVPA) and screen time among youth with overweight/obesity issues who are receiving mental health care. This study looked at a 12-month weight management randomized clinical trial for overweight/obese youth aged 8-18 years who are receiving mental health services. At baseline, MVPA was assessed using accelerometers, and screen time was self-reported. Among 100 youth, 43% were female, 44% were Black, and 48% were <13 years old. In an adjusted general linear model, higher levels of MVPA were associated with the younger age group (p = 0.012), male participants (p = 0.013), and lower BMI z-scores (p = 0.014). In a separate model, higher screen time was associated with participants who were Black (p = 0.007). Achieving optimal cardiovascular health at the population level requires an understanding of the groups that are most in need of additional assistance. These data reinforce that targeted lifestyle approaches to promote increased physical activity and decreased screen time among overweight/obese youth using mental health services may need additional tailoring for sex, age, and race subgroups.

Agent-Based Modeling for Implementation Research: An Application to Tobacco Smoking Cessation for Persons with Serious Mental Illness.

BACKGROUND: Implementation researchers have sought ways to use simulations to support the core components of implementation, which typically include assessing the need for change, designing implementation strategies, executing the strategies, and evaluating outcomes. The goal of this paper is to explain how agent-based modeling could fulfill this role. METHODS: We describe agent-based modeling with respect to other simulation methods that have been used in implementation science, using non-technical language that is broadly accessible. We then provide a stepwise procedure for developing agent-based models of implementation processes. We use, as a case study to illustrate the procedure, the implementation of evidence-based smoking cessation practices for persons with serious mental illness (SMI) in community mental health clinics. RESULTS: For our case study, we present descriptions of the motivating research questions, specific models used to answer these questions, and a summary of the insights that can be obtained from the models. In the first example, we use a simple form of agent-based modeling to simulate the observed smoking behaviors of persons with SMI in a recently completed trial (IDEAL, Comprehensive Cardiovascular Risk Reduction Trial in Persons with SMI). In the second example, we illustrate how a more complex agent-based approach that includes interactions between patients, providers and site administrators can be used to provide guidance for an implementation intervention that includes training and organizational strategies. This example is based in part on an ongoing project focused on scaling up evidence-based tobacco smoking cessation practices in community mental health clinics in Maryland. CONCLUSION: In this paper we explain how agent-based models can be used to address implementation science research questions and provide a procedure for setting up simulation models. Through our examples, we show how what-if scenarios can be examined in the implementation process, which are particularly useful in implementation frameworks with adaptive components.

Effect of a Comprehensive Cardiovascular Risk Reduction Intervention in Persons With Serious Mental Illness: A Randomized Clinical Trial.

Importance: Persons with serious mental illness have a cardiovascular disease mortality rate more than twice that of the overall population. Meaningful cardiovascular risk reduction requires targeted efforts in this population, who often have psychiatric symptoms and cognitive impairment. Objective: To determine the effectiveness of an 18-month multifaceted intervention incorporating behavioral counseling, care coordination, and care management for overall cardiovascular risk reduction in adults with serious mental illness. Design, Setting, and Participants: This randomized clinical trial was conducted from December 2013 to November 2018 at 4 community mental health outpatient programs in Maryland. The study recruited adults with at least 1 cardiovascular disease risk factor (hypertension, diabetes, dyslipidemia, current tobacco smoking, and/or overweight or obesity) attending the mental health programs. Of 398 participants screened, 269 were randomized to intervention (132 participants) or control (137 participants). Data collection staff were blinded to group assignment. Data were analyzed on the principle of intention to treat, and data analysis was performed from November 2018 to March 2019. Interventions: A health coach and nurse provided individually tailored cardiovascular disease risk reduction behavioral counseling, collaborated with physicians to implement appropriate risk factor management, and coordinated with mental health staff to encourage attainment of health goals. Programs offered physical activity classes and received consultation on serving healthier meals; intervention and control participants were exposed to these environmental changes. Main Outcomes and Measures: The primary outcome was the change in the risk of cardiovascular disease from the global Framingham Risk Score (FRS), which estimates the 10-year probability of a cardiovascular disease event, from baseline to 18 months, expressed as percentage change for intervention compared with control. Results: Of 269 participants randomized (mean [SD] age, 48.8 [11.9] years; 128 men [47.6%]), 159 (59.1%) had a diagnosis of schizophrenia or schizoaffective disorder, 67 (24.9%) had bipolar disorder, and 38 (14.1%) had major depressive disorder. At 18 months, the primary outcome, FRS, was obtained for 256 participants (95.2%). The mean (SD) baseline FRS was 11.5% (11.5%) (median, 8.6%; interquartile range, 3.9%-16.0%) in the intervention group and 12.7% (12.7%) (median, 9.1%; interquartile range, 4.0%-16.7%) in the control group. At 18 months, the mean (SD) FRS was 9.9% (10.2%) (median, 7.7%; interquartile range, 3.1%-12.0%) in the intervention group and 12.3% (12.0%) (median, 9.7%; interquartile range, 4.0%-15.9%) in the control group. Compared with the control group, the intervention group experienced a 12.7% (95% CI, 2.5%-22.9%; P = .02) relative reduction in FRS at 18 months. Conclusions and Relevance: An 18-month behavioral counseling, care coordination, and care management intervention statistically significantly reduced overall cardiovascular disease risk in adults with serious mental illness. This intervention provides the means to substantially reduce health disparities in this high-risk population. Trial Registration: ClinicalTrials.gov Identifier: NCT02127671.

Reduced immunity to measles in adults with major depressive disorder.

BACKGROUND: Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. METHODS: IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. RESULTS: Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. CONCLUSIONS: Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

Herpes simplex virus 1 infection and valacyclovir treatment in schizophrenia: Results from the VISTA study.

BACKGROUND: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population. METHODS: 170 subjects with schizophrenia (HSV-1 positive N = 70; HSV-1 negative N = 96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory. RESULTS: The HSV-1 positive group, as compared to the HSV-1 negative group, were older (p < 0.001) with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034) and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 0.045). Valacyclovir failed to significantly improve any of the cognitive indices, symptom or functioning measures. CONCLUSIONS: HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Autoimmune phenotypes in schizophrenia reveal novel treatment targets.

Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.

Need for Cardiovascular Risk Reduction in Persons With Serious Mental Illness: Design of a Comprehensive Intervention.

Persons with serious mental illness (SMI) comprise a high-risk group for cardiovascular disease (CVD)-related mortality with rates at least twice those of the overall US. Potentially modifiable CVD risk behaviors (tobacco smoking, obesity, physical inactivity, unhealthy diet) and risk factors (hypertension, diabetes, dyslipidemia) are all markedly elevated in persons with SMI. Evaluations of programs implementing integrated medical care into specialty mental health settings have not shown meaningful effects on CVD risk factor reduction. Rigorously tested, innovative interventions are needed to address the large burden of CVD risk in populations with SMI. In this article, we describe the design of a comprehensive 18-month intervention to decrease CVD risk that we are studying in a randomized clinical trial in a community mental health organization with psychiatric rehabilitation programs. The individual-level intervention incorporated health behavior coaching and care coordination/care management to address all seven CVD risk behaviors and risk factors, and is delivered by a health coach and nurse. If successful, the intervention could be adopted within current integrated care models and significantly improve the physical health of persons with SMI.

Effects of Cumulative Herpesviridae and Toxoplasma gondii Infections on Cognitive Function in Healthy, Bipolar, and Schizophrenia Subjects.

OBJECTIVE: Schizophrenia and bipolar disorder are associated with cognitive impairment leading to social disruption. While previous studies have focused on the effect of individual infectious exposure, namely, Herpesviridae viruses or Toxoplasma gondii (T gondii), on cognitive functioning, the objective of the present study was to examine the effect of multiple infections on cognitive functioning in patients with schizophrenia and bipolar disorder and in healthy controls. METHODS: Seropositivity to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV), and T gondii was related to cognitive status among 423 participants (recruited between 2008 and 2014; 138 patients with bipolar disorder, 105 patients with schizophrenia [DSM-IV criteria], and 180 healthy controls) for episodic verbal memory (California Verbal Learning Test), working memory (Wechsler Adult Intelligence Scale, third edition), and premorbid intelligence quotient (National Adult Reading Test). RESULTS: Seropositivity to and antibody levels of HSV-1 were significantly associated with working memory, which persisted after correction (backward digit span: ß = -0.10 [0.05], χ² = 33.89, P = .0001) in the overall sample. This association was particularly strong in the control group (ß = -0.18 [0.08], P = .04, Z = -3.55, P = .0008; corrected P = .012). Further, cumulative exposure to HSV-1, HSV-2, and CMV viruses and T gondii parasite was also associated with lower scores on working memory as measured by backward digit span in the overall sample (Z = 2.86, P = .004; Z = 2.47, P = .01; and Z = 3.35, P = .01, respectively). CONCLUSIONS: Exposures to Herpesviridae and T gondii parasite seem to impact cognitive functioning. Because infections caused by Herpesviridae and/or T gondii parasite are quite common in the (general) population, assessing and confirming the cognitive impairment among those who have cumulative exposures is useful and of interest.

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.

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. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut-brain mechanisms.

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.

Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls.

The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls were richer in species but less even in their distributions, i.e., dominated by fewer species, as opposed to schizophrenia patients. Lactic acid bacteria were relatively more abundant in schizophrenia, including species of Lactobacilli and Bifidobacterium, which have been shown to modulate chronic inflammation. We also found Eubacterium halii, a lactate-utilizing species. Functionally, the microbiome of schizophrenia patients was characterized by an increased number of metabolic pathways related to metabolite transport systems including siderophores, glutamate, and vitamin B12. In contrast, carbohydrate and lipid pathways and energy metabolism were abundant in controls. These findings suggest that the oropharyngeal microbiome in individuals with schizophrenia is significantly different compared to controls, and that particular microbial species and metabolic pathways differentiate both groups. Confirmation of these findings in larger and more diverse samples, e.g., gut microbiome, will contribute to elucidating potential links between schizophrenia and the human microbiota.

Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial.

Although peripheral immune system abnormalities have been linked to schizophrenia pathophysiology, standard antipsychotic drugs show limited immunological effects. Thus, more effective treatment approaches are required. Probiotics are microorganisms that modulate the immune response of the host and, therefore, may be beneficial to schizophrenia patients. The aim of this study was to examine the possible immunomodulatory effects of probiotic supplementation in chronic schizophrenia patients. The concentrations of 47 immune-related serum proteins were measured using multiplexed immunoassays in samples collected from patients before and after 14 weeks of adjuvant treatment with probiotics (Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12; n = 31) or placebo (n = 27). Probiotic add-on treatment significantly reduced levels of von Willebrand factor (vWF) and increased levels of monocyte chemotactic protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), RANTES, and macrophage inflammatory protein-1 beta (MIP-1) beta with borderline significance (P ≤ 0.08). In silico pathway analysis revealed that probiotic-induced alterations are related to regulation of immune and intestinal epithelial cells through the IL-17 family of cytokines. We hypothesize that supplementation of probiotics to schizophrenia patients may improve control of gastrointestinal leakage.

Factors influencing implementation of smoking cessation treatment within community mental health centers.

OBJECTIVE: Consumers with serious mental illness smoke more and are at higher risk for smoking-related illness. We examined provider and consumer factors influencing the implementation of the evidence-based "5 A's" (ask, advise, assess, assist, arrange) in six community mental health centers in greater Baltimore. METHODS: Data collected as part of a larger study examining the effectiveness of delivery of the 5 A's at patient visits. First, we examined responses to a survey administered to 49 clinicians on barriers and attitudes toward delivering the 5 A's. Second, we used multilevel models to examine variance between patients (n = 228), patient factors, and variance between their psychiatrists (n = 28) in the delivery of the 5 A's (and first 3 A's). RESULTS: The most strongly endorsed barrier was perceived lack of patient interest in smoking cessation. Psychiatrists and patients both accounted for significant variance in the delivery of the 5 A's and 3 A's. Patient "readiness to change" predicted delivery of the full 5 A's, while smoking severity predicted delivery of the first 3 A's. CONCLUSIONS: There is a critical need for creative and collaborative solutions, policies, and clinician training to address actual and perceived obstacles to the delivery of evidence-based smoking cessation treatment in the mental health care setting.

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.

Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia.

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. As a group, while people with schizophrenia have moderate cognitive impairment, it is the best predictor of long-term outcome. Unfortunately, there are no approved medications for cognitive impairment in this population. Hence, the development of new pharmacological approaches is critical for reducing illness-related disability. The combination of an acetylcholinesterase inhibitor (AChEI) and memantine is more effective than either medication alone to improve cognition in Alzheimer's dementia. Galantamine is not only an AChEI, but also a positive allosteric modulator of the α4ß2 and α7 nicotinic receptors. Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been implicated in the pathophysiology of cognitive symptoms in schizophrenia and hence memantine may positively impact cognition. Memantine decreases the tonic NMDA current and galantamine enhances the action potential mediated by a postsynaptic NMDA current. This results in an increased signal transmission; therefore, a greater signal-to-noise ratio occurs with the combination than memantine alone. Galantamine improves the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)-mediated signaling which could be neuroprotective and may improve memory coding. The combination of galantamine and memantine may be particularly effective in schizophrenia in order to increase the selective cognition enhancement produced by either medication alone. In the future, multitarget-directed ligands may play a role in the treatment of complex diseases like schizophrenia.