The association between toxoplasma and the psychosis continuum in a general population setting

Toxoplasma gondii infection is associated with increased risk for psychosis. However, the possible association between T. gondii and psychotic-like symptoms in the general adult population is unknown. We investigated whether T. gondii is associated with psychotic-like symptoms and psychosis diagnoses using data from Health 2000, a large cross-sectional health survey of the Finnish general population aged 30 and above. Seropositivity to toxoplasma was defined as a cutoff of 50 IU/ml of IgG antibodies. Lifetime psychotic-like symptoms were identified with section G of the Composite International Diagnostic Interview, Munich version (M-CIDI). Symptoms were considered clinically relevant if they caused distress or help-seeking or there were at least three of them. Lifetime psychotic disorders were screened from the sample and were diagnosed with DSM-IV using SCID-I interview and information from medical records. All data were available for 5906 participants. We adjusted for variables related to T. gondii seropositivity (age, gender, education, region of residence, cat ownership, and C-reactive protein measuring inflammation) in regression models. We found that T. gondii seropositivity was significantly associated with clinically relevant psychotic-like symptoms (OR 1.77, p = 0.001) and with the number of psychotic-like symptoms (IRR = 1.55, p = 0.001). The association between toxoplasma and diagnosed psychotic disorders did not reach statistical significance (OR 1.45 for schizophrenia). In a large sample representing the whole Finnish adult population, we found that serological evidence of toxoplasma infection predicted psychotic-like symptoms, independent of demographic factors and levels of C-reactive protein. Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms. (c) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning and risk of dementia in the general population : 11-year follow-up study

Background: Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline, in adults. Method: The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. Results: In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. Conclusions: The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. (C) 2018 Published by Elsevier Inc.Peer reviewe

Exposure to common infections and risk of suicide and self-harm : a longitudinal general population study

Common infectious agents, such as Toxoplasma gondii (T. gondii) and several human herpes viruses, have been linked to increased risk of self-harm. The aim of this study was to investigate the associations between self-harm and seropositivity to T. gondii, Epstein-Barr virus (EBV), Herpes Simplex virus Type 1 (HSV-1), and Cytomegalovirus (CMV). IgM and IgG antibodies to these infections were measured in the Health 2000 project nationally representative of the whole Finnish adult population, and 6250 participants, age 30 and over, were followed for 15 years via registers. In addition, lifetime suicidal ideation and suicide attempts based on medical records and interview were assessed within a subsample of 694 participants screened to a substudy for possible psychotic symptoms or as controls. Among the 6250 participants, 14 individuals died of suicide and an additional 4 individuals had a diagnosis of intentional self-harm during follow-up. Serological evidence of lifetime or acute infections was not found to be associated with these suicidal outcomes. However, in the subsample, those seropositive for CMV had fewer suicide attempts compared to those seronegative, adjusting for gender, age, educational level, childhood family size, regional residence, CRP, and screen status (OR for multiple attempts = 0.40, 95% confidence interval 0.20-0.83, p = 0.014). To conclude, common infections were not associated with risk of death by suicide or with self-harm diagnoses at a 15-year follow-up in the general population sample. Our finding of an increased number of suicide attempts among persons seronegative for CMV calls for further research.Peer reviewe

Studying the virome in psychiatric disease

An overlooked aspect of current microbiome studies is the role of viruses in human health. Compared to bacterial studies, laboratory and analytical methods to study the entirety of viral communities in clinical samples are rudimentary and need further refinement. In order to address this need, we developed Virobiome-Seq, a sequence capture method and an accompanying bioinformatics analysis pipeline, that identifies viral reads in human samples. Virobiome-Seq is able to enrich for and detect multiple types of viruses in human samples, including novel subtypes that diverge at the sequence level. In addition, Virobiome-Seq is able to detect RNA transcripts from DNA viruses and may provide a sensitive method for detecting viral activity in vivo. Since Virobiome-Seq also yields the viral sequence, it makes it possible to investigate associations between viral genotype and psychiatric illness. In this proof of concept study, we detected HIV1, Torque Teno, Pegi, Herpes and Papilloma virus sequences in Peripheral Blood Mononuclear Cells, plasma and stool samples collected from individuals with psychiatric disorders. We also detected the presence of numerous novel circular RNA viruses but were unable to determine whether these viruses originate from the sample or represent contaminants. Despite this challenge, we demonstrate that our knowledge of viral diversity is incomplete and opportunities for novel virus discovery exist. Virobiome-Seq will enable a more sophisticated analysis of the virome and has the potential of uncovering complex interactions between viral activity and psychiatric disease. (c) 2021 Elsevier B.V. All rights reserved.Peer reviewe

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

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

Bringing an Effective Behavioral Weight Loss Intervention for People With Serious Mental Illness to Scale

People with serious mental illnesses (SMIs) die 10–20 years earlier than the general population, mainly due to cardiovascular disease. Obesity is a key driver of cardiovascular risk in this group. Because behavioral weight loss interventions tailored to the needs of people with SMI have been shown to lead to clinically significant weight loss, achieving widespread implementation of these interventions is a public health priority. In this Perspective, we consider strategies for scaling the ACHIEVE behavioral weight loss intervention for people with SMI, shown to be effective in a randomized clinical trial (RCT), to mental health programs in the U.S. and internationally. Given the barriers to high-fidelity implementation of the complex, multi-component ACHIEVE intervention in often under-resourced mental health programs, we posit that substantial additional work is needed to realize the full public health potential of this intervention for people with SMI. We discuss considerations for successful “scale-up,” or efforts to expand ACHIEVE to similar settings and populations as those included in the RCT, and “scale-out,” or efforts to expand the intervention to different mental health program settings/sub-populations with SMI. For both, we focus on considerations related (1) intervention adaptation and (2) implementation strategy development, highlighting four key domains of implementation strategies that we believe need to be developed and tested: staff capacity building, leadership engagement, organizational change, and policy strategies. We conclude with discussion of the types of future research needed to support ACHIEVE scale-up/out, including hybrid trial designs testing the effectiveness of intervention adaptations and/or implementations strategies

Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009

Background: This study examined the use of low doses of antipsychotic medications (300mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates. Methods: Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. Results: The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics. Conclusion: Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophreni

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

Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology