Pilot study indicates that a gluten-free diet lowers oxidative stress for gluten-sensitive persons with schizophrenia.

One-third of people with schizophrenia have elevated levels of anti-gliadin antibodies (AGA IgG). A 5-week randomized double-blind pilot study was performed in 2014-2017 in an inpatient setting to test the effect of a gluten-free diet (GFD) on participants with schizophrenia or schizoaffective disorder who also had elevated AGA IgG (≥ 20 U) but were negative for celiac disease. This earlier pilot study reported that the GFD-group showed improved gastrointestinal and psychiatric symptoms, and also improvements in TNF-α and the inflammatory cytokine IL-23. Here, we performed measurements of these banked plasma samples to detect levels of oxidative stress (OxSt) using a recently developed iridium (Ir)-reducing capacity assay. Triplicate measurements of these samples showed an Intraclass Correlation Coefficient of 0.84 which indicates good reproducibility. Further, a comparison of the OxSt measurements at the baseline and 5-week end-point for this small sample size shows that the GFD-group (N = 7) had lowered OxSt levels compared to the gluten-containing diet group (GCD; N = 9; p = 0.05). Finally, we showed that improvements in OxSt over these 5 weeks were correlated to improvements in gastrointestinal (r = +0.64, p = 0.0073) and psychiatric (r = +0.52, p = 0.039) symptoms. Also, we showed a possible association between the decrease in OxSt and the lowered levels of IL-23 (r = +0.44, p = 0.087), although without statistical significance. Thus, the Ir-reducing capacity assay provides a simple, objective measure of OxSt with the results providing further evidence that inflammation, redox dysregulation and OxSt may mediate interactions between the gut and brain.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

Association of Psychotic Experiences and Incident Depression in a Longitudinal Population-Based Community Survey.

Objective: The present study aims to determine if psychotic experiences in a general population sample are a risk factor for depressive disorders at a 15-year follow-up visit. Method: A longitudinal population cohort of adults over age 18 from East Baltimore were followed from 1981 to 1996 with 1409 participants included in analyses. Delusions and hallucinations and depressive disorders were assessed using DSM-III criteria. Odds ratios were obtained using logistic regression with psychotic experiences modeled both dichotomously and as count variables as predictors of major and minor depressive disorders at wave three. Age, race, and sex were included as covariates in the model. Results: Both delusions and hallucinations were associated with an increased odds of incident depressive disorders. Delusions, but not hallucinations, were associated with increased odds of major depressive disorder (adjusted odds ratio, 3.04 [95% CI = 1.29-7.13]) and both delusions and hallucinations were associated with increased odds of minor depressive disorder (adjusted odds ratios, 4.6 [95% CI = 2.11-10.04] and 3.93 [95% CI = 2.11-7.32]). There was a dose-response relationship in number of psychotic experiences reported and odds of depressive disorders. Conclusions: Lifetime psychotic experiences, particularly delusions, in the absence of mental disorders, are associated with later depressive disorders. Results persist in a dose-response manner. Future research should determine whether transitory versus persistent psychotic experiences have a differential effect on later depression.

Immunologic profiling in schizophrenia and rheumatoid arthritis.

The negative relationship between schizophrenia (SCZ) and rheumatoid arthritis (RA) has been observed for 85 years, but the mechanisms driving this association are unknown. This study analyzed differences in profiles of cytokines (IL-1ß, IL-Ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IFNγ, TNFα), selected genes (HLA-DRB1, IL1RN, HP2), and antibodies related to gluten sensitivity (AGA-IgG, AGA-IgA), celiac disease (tTG), and systemic autoimmunity (ANA, anti-CCP, RF) in 40 subjects with SCZ, 40 with RA, and 40 healthy controls (HC). HLA-DRB1*04:01 alleles were enriched in persons with SCZ and RA compared with HC, and the HP2/HP2 genotype was 2-fold more prevalent in AGA/tTG-positive versus negative SCZ patients. Patients with SCZ demonstrated 52.5% positivity for any of the antibodies tested, compared to 90% of RA patients and 30% of HC. Cluster analysis of the cytokines revealed three clusters: one associated with SCZ marked by high levels of IL-1Ra, one associated with HC, and one associated with both SCZ and RA marked by elevated levels of IFNγ, TNFα, and IL-6. These analyses suggest that stratification of SCZ patients by cytokine profile may identify unique SCZ subgroups and enable the use of currently available cytokine-targeted treatment strategies.

The Relationship Between Latinxs' Acculturative Experiences and Mental and Behavioral Disorder in the National Latino and Asian American Study.

Mental and behavioral disorders are among the leading contributors to disability among US-residing Latinxs. When treated as a homogeneous group, important disparities in the prevalence of such disorders among Latinx subgroups (e.g., by ethnic heritage) are obscured. However, Latinxs may also be characterized by their acculturative experiences while living in the USA, such as discrimination, neighborhood context and family conflict. Latent Profile Analysis with distal outcomes was used to estimate differences in psychiatric disorder prevalence across acculturative subgroups. Data from 2,541 Latinx participants (age 18 +) in the National Latino and Asian American Study (NLAAS) were used to estimate differences in the proportion of three categories of DSM-IV disorder: depressive, anxiety and substance use by four latent subgroups of Latinxs based on their acculturative experiences. Latinxs reporting more positive acculturative experiences had the lowest prevalence of all three disorders (14.8%, 13.6% and 7.1%, respectively). Those whose lives were characterized by high levels of family conflict and discrimination combined with low levels of social cohesion and neighborhood safety had the highest disorder prevalence (34.0%, 26.6% and 22.5%; all p < 0.01 compared to positive experiences subgroup). Latinxs with moderate levels of discrimination and conflict, along with those with high conflict and cohesion, were better off as compared to those with high negative experiences and low cohesion. These latent subgroups of Latinxs according to their acculturative experiences hold important implications for identifying high-risk groups for developing a psychiatric disorder. Findings also point to the protective role of family and neighborhood cohesion when facing high levels of adversity, which may inform prevention and intervention efforts.

The association between traumatic life events and insomnia symptoms among men and women: Results from the Baltimore Epidemiologic Catchment Area follow-up study.

STUDY OBJECTIVES: Trauma exposure likely contributes to poor sleep, but relatively few studies have empirically tested this, instead focusing on posttraumatic stress disorder. Moreover, little is known about sex differences in sleep after trauma. The current study used a cross-sectional and retrospective design to test hypotheses that trauma exposure would be associated with subsequent insomnia symptoms, particularly among women, even after accounting for important covariates. METHOD: Data from Wave 3 (1993-1996) of the Baltimore Epidemiologic Catchment Area Study (N = 1920) were used to examine associations between remote (prior to past year) and recent (past year) trauma and current sleep disturbance (insomnia, hypersomnia symptoms) in the total sample (Mage= 55, 63.2% women, 57.7% white), and separately in men and women. Sensitivity analyses were conducted among individuals with no pretrauma sleep disturbance to examine incident sleep disturbance. RESULTS: Among all participants, both remote (odds ratio [OR] = 1.95, 95% confidence interval [CI] [1.34, 2.85]) and recent (OR = 1.94, 95% CI [1.31, 2.87]) trauma exposure were associated with increased odds of insomnia (OR = 2.41, 95% CI [1.54, 3.76]) but not hypersomnia. Associations between trauma and insomnia were particularly strong among women, but null among men. The relationship between trauma exposure and insomnia symptoms persisted among individuals with no pretrauma history of insomnia. CONCLUSION: Results suggest women may be vulnerable to insomnia symptoms as sequelae of trauma. Future research should examine prospective associations between trauma and sleep in larger samples and how assessment and treatment of insomnia among women trauma survivors reduces the public health impact of trauma and poor sleep.

The relationship between social and environmental factors and symptom severity in the seriously mentally ill population.

BACKGROUND: The goal of this article is to investigate the relationship of psychiatric symptom severity with internalised stigma, neighbourhood environment, and social support among individuals with serious mental illness. METHOD: Using a longitudinal study design we examined the relationship between psychiatric symptom severity with internalised stigma, neighbourhood environment, and social support among 271 adults with serious mental illness recruited from new admissions to two urban mental health clinics. RESULTS: After controlling for demographics increased stigma levels predicted greater symptom severity, as measured by the Positive and Negative Syndrome Scale (PANSS) Positive, Negative, and General Psychopathology scales over a 4-year period (p < .05). In adjusted models, individuals who reported living in more disadvantaged neighbourhoods also reported higher PANSS Negative and General scores over time (p < .05). Social support from friends and relatives was not significantly related to PANSS Positive, Negative, or General Psychopathology scores among individuals with serious mental illness. CONCLUSIONS: Individuals with serious mental illness who experience internalised stigma and neighbourhood disadvantage experience greater symptom severity over time. Targeting stigma and housing during treatment could potentially impact symptom severity in this population.

Symptom Severity and Care Delay among Patients with Serious Mental Illness.

PURPOSE: This study investigated associations between psychiatric symptom severity and delay in seeking general medical services among individuals with serious mental illness. METHODS: The association of psychiatric symptom severity, measured by the Positive and Negative Syndrome Scale (PANSS), and general medical care delay was examined among 271 patients at two urban, outpatient psychiatric clinics. RESULTS: Higher scores for PANSS paranoid/belligerence were associated with delays in accessing general medical care (adjusted odds ratio [AOR]=1.46, 95% confidence interval [CI]=1.04-2.01, p=.025). Higher scores on the depression symptom cluster were also associated with care delay (AOR=1.43, 95% CI=1.06-1.93, p=.018). Other symptom types showed no associations with care delay. CONCLUSION: Severity of specific psychiatric symptoms was associated with delays in seeking general medical care among people with serious mental illness. Increased focus on psychiatric symptom management may reduce medical care delay, thereby reducing the elevated morbidity and mortality among this population.

Depression in a youth population-based sample from Brazil: Prevalence and symptom structure.

BACKGROUND: We aimed to examine the occurrence of major depressive disorder (MDD) in a population-based youth sample, assessing both categorical and dimensional presentations of the disorder and its clinical and sociodemographic correlates. METHODS: We analyzed cross-sectional data from the latest assessment of the 1993 Pelotas Birth Cohort (n = 3,780), a population-based study from Brazil that followed individuals up to age 22 years. We estimated point-prevalence for categorical diagnosis of MDD and comorbid diagnoses using DSM criteria in a structured interview by trained psychologists. Dimensional symptomatology was assessed with the Brazilian Portuguese version of the Center for Epidemiological Studies-Depression Scale-Revised (CES-D-R). RESULTS: Point-prevalence of a current unipolar major depressive episode was 2.85% (95%CI 2.37-3.43%). The CES-D-R showed a mean of 9.20 (SD=9.72), with an area under the curve of 0.93 (95%CI 0.91 to 0.95) for the categorical diagnosis of MDD using a cutoff point of 16. Sad mood and somatic symptoms were the most frequent, and also had lower levels of latent values required for endorsement. Sad mood and anhedonia items were the most central items in the network structure. CONCLUSIONS: In a population-based sample of youths from a middle-income country, MDD prevalence estimates and comorbidity profile were consistent with previous global literature. A focus on symptoms might advance our understanding about MDD among youths by disentangling the heterogeneity of the disorder.

Factor structure and invariance analysis of the center for epidemiologic studies depression scale - revised (CESD-R) in a Brazilian population / Estrutura Fatorial e Análise de Invariância da Center for Epidemiologic Studies Depression Scale - Revised (CESD-R) em uma População Brasileira

Abstract Introduction: The Center for Epidemiologic Studies Depression Scale - Revised (CESD-R) was developed to provide an efficient screening scale for depression syndrome, mimicking the original CESD, one of the most widely used screening tools to measure depressive symptoms globally. This investigation examined the factor structure of the CESD-R with a non-clinical Brazilian population. Method: We performed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of two adult samples, and also conducted invariance analysis by sex and place of residence of the participants. The full sample consisted of 1,427 adults, divided into two groups. The first sample (n = 400) was used for the EFA and the second sample (n = 1027) for the CFA. Results: The EFA indicated an internal structure composed of a single factor, which explained 53.2% of the variance. The CFA attested to the unidimensionality of the measure. Fit indices and reliability indicators showed values higher than expected, without modifications in the initial structure. The model was invariant in relation to the variables investigated at four different levels (configural, metric, scalar, and strict). Conclusions: Our findings support the utility of the CESD-R and suggest its validity for application to the Brazilian population in general.

Resumo Introdução: A Center for Epidemiologic Studies Depression Scale - Revised (CESD-R) foi elaborada para fornecer um eficiente diagnóstico de sintomas de depressão, seguindo a proposta original da CESD, que é uma das escalas para rastreamento da depressão mais utilizadas mundialmente. Esta pesquisa avaliou a estrutura fatorial da CESD-R em uma população não-clínica no Brasil. Método: Realizaram-se análises fatoriais exploratória (AFE) e confirmatória (AFC) com duas amostras compostas por adultos. Também foi verificada a invariância do modelo por sexo e local de residência do participante. A amostra total foi composta por 1427 adultos, tendo sido dividida em duas subamostras. A primeira subamostra (n = 400) foi utilizada para a AFE e a segunda (n = 1027) para a AFC. Resultados: A AFE indicou uma estrutura interna composta por um único fator, que explicou 53.2% de variância. A AFC atestou unidimensionalidade da medida. Os índices de ajuste e indicadores de confiabilidade apresentaram valores acima do esperado, sem modificações na estrutura inicial. O modelo foi invariante em relação às variáveis investigadas em quatro diferentes níveis (configural, métrico, escalar e estrito). Conclusões: Os presentes achados suportam a utilidade da CESD-R e sugerem sua validade para aplicação na população brasileira.

Symptom severity and medication-assisted treatment for individuals with serious mental illness and a history of heroin use.

The study examined associations between medication assisted treatment (MAT) and psychiatric symptom severity, measured by Positive and Negative Symptom Scale (PANSS), among individuals with serious mental illness and a history of heroin use. Of 271 participants, 32% (n=87) reported a history of heroin use and, of those, 14.9% (n=13) reported MAT. Higher scores in PANSS Total, Negative, and Disordered subscales were associated with lower odds, while being on an antipsychotic with higher odds, of receiving MAT. This supports the greater need for clinician attention to different symptom clusters and targeted multidimensional interventions as a way to increase MAT participation.

From population to neuron: exploring common mediators for metabolic problems and mental illnesses.

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.

The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study.

BACKGROUND: The human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. METHODS: 628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. RESULTS: The SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a "protective" association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers CONCLUSIONS: The findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.

Refining acculturation measures for health research: Latina/o heterogeneity in the National Latino and Asian American Study.

OBJECTIVES: This study factor analyzes six scales relating to acculturation and related experiences among a nationally representative sample of United States-residing Latina/os (n = 2,541) from the National Latino and Asian American Study (NLAAS), using measurement invariance (MI) testing to explore differences in latent constructs by Latina/o subgroup. METHODS: Factor Analysis (FA) within an Exploratory Structural Equation Modeling framework was used to analyze the factor structure of six scales measuring acculturation and related experiences (i.e., acculturation [language use and preference], enculturation [ethnic identity], discrimination, neighborhood context, and family environment). We tested for MI by two important Latina/o subgroups: ethnic heritage and generational status. RESULTS: The underlying latent factors resulting from FA strongly aligned with the NLAAS subscales. No scale achieved full MI, yet the degree to which MI held varied greatly by scale and by subgroup. CONCLUSIONS: Findings show that Latina/os are heterogeneous, but that this often depends on the construct and subgrouping of interest. Future research should use these scales in a latent framework, accounting for the lack of MI, to ensure that the underlying acculturative constructs of interest are validly measured when investigating their association with mental health outcomes in this population.

Clinical outcomes from the texting for relapse prevention (T4RP) in schizophrenia and schizoaffective disorder study.

This 6 month randomized control trial investigated whether a novel text-messaging program impacted targeted clinical outcomes in patients with schizophrenia and schizoaffective disorder (SAD). Forty patients were enrolled and completed baseline, 3-month and 6-month assessments. The intervention group received daily symptom check-in text messages, plus, a medication reminder or, inspirational quote text. The control group had treatment as usual. At 6 months the Positive and Negative Syndrome Scale mean positive score was significantly lower and injectable medication compliance was significantly higher in the intervention group. Recovery scores were significantly higher at 3 months. Results suggest that this program may benefit individuals with schizophrenia/SAD who use text messaging. Further investigation in a larger sample appears warranted.

A Diagnostic-Oriented Screening Scale for Anxiety Disorders: The Center for Epidemiologic Studies Anxiety Scale (CESA).

OBJECTIVES: This paper introduces a new diagnostically oriented screening scale for anxiety disorders, the Center for Epidemiologic Studies Anxiety scale (CESA), designed in parallel to the revised Center for Epidemiologic Studies Depression scale (CESD-R). In this study, the CESA was used as a diagnostic screening tool for detecting the presence of anxiety disorder symptomatology ascertained by a clinical psychiatric evaluation based on the DSM-5 criteria. The CESA is designed to provide an overall evaluation of anxiety as well as to screen for four important anxiety disorders (agoraphobia, social phobia, blood-illness phobia, and panic disorder). METHODS: The test sample was composed of 80 adults seeking treatment for mental problems in a general psychiatric clinic. We assessed the receiver operating characteristic (ROC) curve of the CESA in comparison to the psychiatric interview. RESULTS: The main findings suggest that the CESA is useful for screening for anxiety in general (alpha coefficient of 0.83), as well as for the four common anxiety disorders. The criterion validation confirmed a high level of compatibility between the CESA and the psychiatric evaluation. CONCLUSION: This is the initial report regarding the CESA and future research will focus on specific aspects of criterion validity for each disorder.

Financial hardship among individuals with serious mental illness.

This study explored financial hardship, defined as difficulty in obtaining food, shelter, or medicine in the past 12 months and its personal and clinical correlates in individuals with serious mental illness (SMI) in a sample of 271 adults with SMI newly admitted to two inner city community mental health centers. The study found that 59 percent (n = 161) reported experiencing financial hardship in the past 12 months. Patients with financial hardship were more likely to be female, to experience self-stigma, to experience medical care delays, and to use emergency services. Patients who experienced financial hardship typically had more severe psychiatric symptoms, including depressive symptoms, emotional lability, and interpersonal problems. Financial hardship persisted in nearly half of those with hardship interviewed a year later. The findings highlight the role of multiple social and economic challenges that the SMI patients face in recovery from serious mental illness and the importance of awareness of such challenges by providers treating this population. Though mental health treatment may help alleviate the psychiatric symptoms it alone is not sufficient in addressing persistent hardship. These findings highlight the need for multidisciplinary interventions in order to better serve this vulnerable population.