A longitudinal study of the association between persistent pathogens and incident depression among older U.S. Latinos

Depression is estimated to affect more than 6.5 million Americans 65 years of age and older and compared with non-Latino whites older U.S. Latinos have a greater incidence and severity of depression, warranting further investigation of novel risk factors for depression onset among this population. We used data on 771/1,789 individuals ≥60 years of age from the Sacramento Area Latino Study on Aging (1998-2008) who were tested for cytomegalovirus (CMV), herpes simplex virus, varicella zoster, Helicobacter pylori, Toxoplasma gondii, and C-reactive protein (CRP) and interleukin-6 (IL-6) level. Among those without elevated depressive symptoms at baseline, we examined the association between each pathogen, inflammatory markers and incident depression over up to nearly 10 years of follow-up using discrete-time logistic regression. We found that only CMV seropositivity was statistically significantly associated with increased odds of incident depression (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.00-1.90) in the total sample as well as among women only (OR: 1.70, 95% CI: 1.01-2.86). These associations were not mediated by CRP or IL-6 levels. Our findings suggest that CMV seropositivity may serve as an important risk factor for the onset of depression among older U.S. Latinos, but act outside of inflammatory pathways

Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD

Potential Biomarkers Selection for Bipolar Disorder Identification

A biomarker is a measurable indicator of the severity or presence of some disease. A biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. The space Decomposition-Gradient-Regression (DGR) method has been developed (Li et al., 2012; Li et al., 2015) to select biomarkers for schizophrenia. This study performs the DGR approach on data for bipolar disorder patients, which contains 56 biomarkers and 8 infectious agent’s antibodies. Serum specimens were collected from 132 United States military service members (118 males and 14 females) with a diagnosis of bipolar disorder from 1992 to 2005 and their matched healthy controls.. Trefoil Factor3 (TFF3), Gliadin, prolactin (PRL), Apolipoprotein A-II (Apo A-II) and Immunoglobulin A (IGA) were found to be significant predictors of Bipolar Disorder (BD) in males. Macrophage-Derived Chemokine (MDC), Alpha-1-Antitrypsin (AAT), Gliadin, Beta-2-Microglobulin (B2M) and Monocyte Chemotactic Protein 2 (MCP-2) might be used to identify bipolar disorder in females. A predictive biomarker panel for BD offers the potential to aid in the diagnosis, initiate treatment earlier and ideally alter the course of disease with reduced morbidity and functional impairment

Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment.

Complex interactions between the immune system and the brain might have important aetiological and therapeutic implications for neuropsychiatric brain disorders. A possible association between schizophrenia and the immune system was postulated over a century ago, and is supported by epidemiological and genetic studies pointing to links with infection and inflammation. Contrary to the traditional view that the brain is an immunologically privileged site shielded behind the blood-brain barrier, studies in the past 20 years have noted complex interactions between the immune system, systemic inflammation, and the brain, which can lead to changes in mood, cognition, and behaviour. In this Review, we describe some of the important areas of research regarding innate and adaptive immune response in schizophrenia and related psychotic disorders that, we think, will be of interest to psychiatric clinicians and researchers. We discuss potential mechanisms and therapeutic implications of these findings, including studies of anti-inflammatory drugs in schizophrenia, describe areas for development, and offer testable hypotheses for future investigations.The work was supported by a doctoral clinical research training fellowship grant from the Wellcome Trust to Golam Khandaker (094790/Z/10/Z; 2010-‘13), grants from the Stanley Medical Research Institute and the National Institutes of Mental Health (grant# MH-94268) to Robert Yolken, and grants from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z), and the NIHR (RP-PG-0606-1335) to Peter Jones.This is the accepted manuscript. The final version is available from Elsevier at http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366%2814%2900122-9/abstrac

Characteristics of events in which police responded to overdoses: an examination of incident reports in Rhode Island

Background: Narrow or non-existent Good Samaritan Law protections and harsh drug selling statutes in the USA have been shown to deter bystanders from seeking medical assistance for overdoses. Additionally, little is known about the actions that police take when responding to overdose events. The objectives of this study were to assess the prevalence and correlates of naloxone administration by police, as well as to examine overdose events where arrests were made and those in which the person who overdosed was described as combative. Methods: We analyzed incident reports of police responding to an overdose between September 1, 2019, and August 31, 2020 (i.e., 6 months prior to and during the COVID-19 pandemic), from a city in Rhode Island. We examined characteristics of incidents, as well as individual characteristics of the person who overdosed. Correlates of police naloxone administration were assessed using Wilcoxon rank sum tests and Fisher’s exact tests, and we examined incidents where arrests occurred and incidents in which the person who overdosed was described as combative descriptively. Results: Among the 211 incidents in which police responded to an overdose during the study period, we found that police administered naloxone in approximately 10% of incidents. In most incidents, police were the last group of first responders to arrive on scene (59%), and most often, naloxone was administered by others (65%). Police were significantly more likely to administer naloxone when they were the first professionals to arrive, when naloxone had not been administered by others, and when the overdose occurred in public or in a vehicle. Arrests at overdose events were rarely reported (1%), and people who overdosed were rarely (1%) documented in incident reports as being ‘combative.’ Conclusions: Considering these findings, ideally, all jurisdictions should have sufficient first responder staffing and resources to ensure a rapid response to overdose events, with police rarely or never dispatched to respond to overdoses. However, until this ideal can be achieved, any available responders should be dispatched concurrently, with police instructed to resume patrol once other professional responders arrive on scene; additionally, warrant searches of persons on scene should be prohibited

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

Persistent Herpesvirus Infections and Telomere Attrition Over 3 Years in the Whitehall II Cohort

The determinants of telomere attrition, a potential marker of cellular aging, are not well understood. Persistent herpesvirus infections including cytomegalovirus (CMV) infection may be particularly important for telomere dynamics via mechanisms such as inflammation, oxidative stress, and their impact on peripheral blood lymphocyte composition. This study examined the association of 4 human herpesviruses (CMV, herpes simplex virus type 1, human herpesvirus type 6, and Epstein-Barr virus) with change in leukocyte telomere length (LTL) over 3 years in 400 healthy individuals (aged 53–76 years) from the Whitehall II cohort. CMV, herpes simplex virus type 1, and human herpesvirus 6 infection were independently associated with greater 3-year LTL attrition, with no association found for Epstein-Barr virus. The magnitudes of these associations were large, for example, the equivalent of almost 12 years of chronological age for those CMV seropositive. Seropositivity to more herpesviruses was additively associated with greater LTL attrition (3 herpesviruses vs none, β = −0.07 and P = .02; 4 infections vs none, β = −0.14 and P < .001). Higher immunoglobulin G antibody levels among those seropositive to CMV were also associated with shorter LTL at follow-up. These associations were robust to adjustment for age, sex, employment grade, body mass index, and smoking status. These results suggest that exposure to infectious agents should be an important consideration in future studies of telomere dynamics

Immune Dysregulation and Self-Reactivity in Schizophrenia: Do Some Cases of Schizophrenia Have an Autoimmune Basis?

Schizophrenia affects 1% of the world's population, but its cause remains obscure. Numerous theories have been proposed regarding the cause of schizophrenia, ranging from developmental or neurodegenerative processes or neurotransmitter abnormalities to infectious or autoimmune processes. In this review, findings suggestive of immune dysregulation and reactivity to self in patients with schizophrenia are examined with reference to criteria for defining whether or not a human disease is autoimmune in origin. Associations with other autoimmune diseases and particular MHC haplotypes, increased serum levels of autoantibodies, and in vivo and in vitro replication of some of the functional and ultrastructural abnormalities of schizophrenia by transfer of autoantibodies from the sera of patients with schizophrenia suggest that, in some patients at least, autoimmune mechanisms could play a role in the development of disease. Recent findings regarding specific autoimmune responses directed against neurotransmitter receptors in the brain in patients with schizophrenia will also be reviewed