Youth Psychotic Experiences: Diagnostic Associations and Evaluation of the CAPE-16.

Background: Adolescent self-reported psychotic experiences are associated with mental illness and could help guide prevention strategies. The Community Assessment of Psychic Experiences (CAPE) was developed over 20 years ago. In a rapidly changing society, where new generations of adolescents are growing up in an increasingly digital world, it is crucial to ensure high reliability and validity of the questionnaire. Methods: In this observational validation study, we used unique transgenerational questionnaire and health registry data from the Norwegian Mother, Father, and Child Cohort, a population-based pregnancy cohort. Adolescents, aged ~14 years, responded to the CAPE-16 (n = 18,835) and fathers to the CAPE-9 questionnaire (n = 28,793). We investigated the psychometric properties of CAPE-16 through factor analyses, measurement invariance testing across biological sex, response before/ during the COVID-19 pandemic, and generations (comparison with fathers), and examined associations with later psychiatric diagnoses. Outcomes: One third (33·4%) of adolescents reported lifetime psychotic experiences. We confirmed a three-factor structure (paranoia, bizarre thoughts, and hallucinations) of CAPE-16, and observed good scale reliability of the distress and frequency subscales (ω = ·86 and ·90). CAPE-16 measured psychotic experiences were invariant to biological sex and pandemic status. CAPE-9 was non-invariant across generations, with items related to understanding of the digital world (electrical influences) prone to bias. CAPE-16 sum scores were associated with a subsequent psychiatric diagnosis, particularly psychotic disorders (frequency: OR = 2·06; 97·5% CI = 1·70-2·46; distress: OR = 1·93; 97·5% CI = 1·63-2·26). Interpretation: CAPE-16 showed robust psychometric properties across sex and pandemic status, and sum scores were associated with subsequent psychiatric diagnoses, particularly psychotic disorders. These findings suggest that with certain adjustments, CAPE-16 could have value as a screening tool for adolescents in the modern, digital world. Funding: European Union's Horizon 2020 Programme, Research Council of Norway, South-Eastern Norway Regional Health Authority, NIMH, and the KG Jebsen Stiftelsen.

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.

Acceptability of Texting 4 Relapse Prevention, Text Messaging-Based Relapse Prevention Program for People With Schizophrenia and Schizoaffective Disorder.

ABSTRACT: We report process outcomes of the pilot randomized controlled trial of Texting 4 Relapse Prevention (T4RP), a text messaging-based relapse prevention program for people with schizophrenia or schizoaffective disorder (SAD). Forty people were randomized to either the intervention or treatment as usual control group at a 2:1 ratio. Process indicators were collected at 6 months post enrollment.Over 90% of patients agreed or strongly agreed that the text messages were easy to understand, easy to answer, positive, and helped them feel supported. Patient acceptability was positively associated with recovery (ß = 0.29, p = <0.001) and patient-provider communication scores (ß = 1.04, p < 0.001), and negatively associated with symptoms of the disorder (ß = -0.27, p = 0.07). Acceptability was similar by diagnosis (ß, SAD diagnosis = 0.40, p = 0.90) and age (ß = 0.05, p = 0.67). Findings suggest that a text messaging intervention aimed at preventing relapse is feasible and perceived as beneficial in individuals with schizophrenia and SAD. Future research might include a targeted study of T4RP within the context of hospital discharge when people with schizophrenia/SAD are at highest risk of relapse.

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.

Assessing Self-reported Recovery in a Community Psychiatry Setting.

OBJECTIVE: This study examined demographic and diagnostic characteristics associated with self-reported recovery in patients with serious mental illness. METHODS: Patient demographics and diagnoses were obtained from a retrospective review of charts from 981 patients attending a community psychiatry outpatient program between January 2015 and December 2016. All patients completed the Recovery Assessment Scale-Revised (RAS-R), a self-report recovery questionnaire consisting of 5 subscales, approximately every 6 months. Generalized estimating equation models were used to assess change in RAS-R scores over time and to test for associations with demographic characteristics, clinical diagnoses, and appointment adherence. RESULTS: RAS-R scores increased among all demographic and diagnostic groups during the study period. A primary diagnosis of a psychotic disorder (including schizophrenia) was associated with higher 2-year average RAS-R total scores and scores on the Personal Confidence and Hope, Goal and Success Orientation, and Not Dominated by Symptoms subscales. African American race was associated with higher 2-year average scores on the Personal Confidence and Hope subscale. Increasing age was associated with higher total RAS-R scores and multiple subscale scores. No significant associations were found between sex or appointment adherence and RAS-R total scores or any of the subscale scores. CONCLUSIONS: While certain demographic and diagnostic groups were associated with higher RAS-R scores, study results suggest that time in treatment is itself associated with higher self-reported recovery among all demographic groups. Age, race, and diagnosis were all associated with higher scores on the Personal Confidence and Hope subscale, highlighting the need for individualized treatment that takes multiple patient characteristics into account.

Endothelial Stromal PD-L1 (Programmed Death Ligand 1) Modulates CD8+ T-Cell Infiltration After Heart Transplantation.

BACKGROUND: The role of checkpoint axes in transplantation has been partially addressed in animal models but not in humans. Occurrence of fulminant myocarditis with allorejection-like immunologic features in patients under anti-PD1 (programmed death cell protein 1) treatment suggests a key role of the PD1/PD-L1 (programmed death ligand 1) axis in cardiac immune homeostasis. METHODS: We cross-sectionally studied 23 heart transplant patients undergoing surveillance endomyocardial biopsy. Endomyocardial tissue and peripheral blood mononuclear cells were analyzed by flow cytometry. Multivariate logistic regression analyses including demographic, clinical, and hemodynamic parameters were performed. Murine models were used to evaluate the impact of PD-L1 endothelial graft expression in allorejection. RESULTS: We found that myeloid cells dominate the composition of the graft leukocyte compartment in most patients, with variable T-cell frequencies. The CD (cluster of differentiation) 4:CD8 T-cell ratios were between 0 and 1.5. The proportion of PD-L1 expressing cells in graft endothelial cells, fibroblasts, and myeloid leukocytes ranged from negligible up to 60%. We found a significant inverse logarithmic correlation between the proportion of PD-L1+HLA (human leukocyte antigen)-DR+ endothelial cells and CD8+ T cells (slope, -18.3 [95% CI, -35.3 to -1.3]; P=0.030). PD-L1 expression and leukocyte patterns were independent of demographic, clinical, and hemodynamic parameters. We confirmed the importance of endothelial PD-L1 expression in a murine allogeneic heart transplantation model, in which Tie2Crepdl1fl/fl grafts lacking PD-L1 in endothelial cells were rejected significantly faster than controls. CONCLUSIONS: Loss of graft endothelial PD-L1 expression may play a role in regulating CD8+ T-cell infiltration in human heart transplantation. Murine model results suggest that loss of graft endothelial PD-L1 may facilitate alloresponses and rejection.

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.

Sex Differences in the Gut-Brain Axis: Implications for Mental Health.

PURPOSE OF REVIEW: The purpose of this article is to highlight how sex differences in the gut-brain axis may contribute to the discrepancies in incidence of neurodevelopmental, psychiatric, and neurodegenerative disorders between females and males. We focus on autism spectrum disorder, psychotic disorders, stress and anxiety disorders, depression, Alzheimer's disease, and Parkinson's disease and additionally discuss the comorbidity between inflammatory bowel disorder and mental health disorders. RECENT FINDINGS: Human and animal studies show that sex may modify the relationship between the gut or immune system and brain and behavior. Sex also appears to modify the effect of microbial treatments such as probiotics and antibiotics on brain and behavior. There is emerging evidence that assessing the role of sex in the gut-brain axis may help elucidate the etiology of and identify effective treatments for neurodevelopmental, psychiatric, and neurodegenerative disorders.

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.

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.

Developing Texting for Relapse Prevention: A Scalable mHealth Program for People With Schizophrenia and Schizoaffective Disorder.

Symptom relapse in people with schizophrenia and schizoaffective disorder is common and has a negative impact on the course of illness. Here, we describe the development of Texting for Relapse Prevention, a scalable, cost-effective text messaging relapse prevention program that queries patients' "early warning signs" daily. Results of development focus groups and content advisory teams with 25 patients and 19 providers suggest that patients were enthusiastic about the program and thought that receiving daily messages about their symptoms would help them feel supported. Providers also were positive about the idea but worried that the program might interfere with patient-provider communication if patients thought that the messages were coming from providers. Patients found the content positive and actionable. The program was improved to address this feedback. This iterative development process that included multiple stakeholders ensured that the program is feasible and acceptable to both patients and providers.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) ­ a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = ­0.75) and in negative symptoms (Cohen d = ­0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG).

About one third of people with schizophrenia have elevated IgG antibodies to gliadin (AGA IgG) and increased inflammation. Understanding the mechanism by which this immune response occurs is critical to the development of personalized treatments. We examined gut permeability and mimicry to the glutamate receptor as possible mechanisms related to high gliadin antibodies (AGA IgG) seen in some people with schizophrenia. The Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) has a similar protein structure to gliadin representing a potential target for cross reactivity or mimicry. In a population of schizophrenia subjects (N = 160) and healthy controls (N = 80) we analyzed serum samples for both GRINA and Anti-Saccharomyces Cerevisiae antibodies (ASCA), related to gut permeability. Schizophrenia patients compared to controls had a higher prevalence of positivity to ASCA IgA (p = 0.004) and IgG (p < 0.001). Multinomial logistic regression showed an association between AGA IgG and ASCA IgG in schizophrenia (p = 0.05 for the estimated regression coefficient) but not in healthy controls (p = 0.13). GRINA IgG was higher in schizophrenia patients than in healthy controls (0.43 ±â€¯0.30 vs. 0.22 ±â€¯0.24, p < 0.001). Logistic regressions showed an association between AGA IgG and GRINA IgG in schizophrenia (p = 0.016 for the estimated regression coefficient) but not for the controls (p = 0.471). Thus, we propose that mimicry through the presence of cross-reactivity between gliadin and GRINA might disrupt the functions of the glutamate system and relate to illness pathophysiology in those with schizophrenia and elevated AGA IgG.

Prescription opioid use among individuals with serious mental illness.

Prevalence and correlates of prescription opioid use were explored in individuals with serious mental illness (SMI) by examining a sample of adults from two inner city community psychiatry clinics. Of 271 participants, 12.9% (n = 35) were on a prescribed opioid. Being on an opioid was significantly associated with history of heroin use and active prescription sedative-hypnotic use, including benzodiazepine use. Concurrent use of opioids with sedative-hypnotics was significantly associated with suicidal ideation. The results highlight risks of prescription opioid use in those with SMI, particularly in combination with prescription sedative-hypnotics.

Delays in Seeking General Medical Services and Measurable Abnormalities Among Individuals With Serious Mental Illness.

OBJECTIVE: The study explored the association of delays in seeking general medical care with elevated blood pressure and metabolic abnormalities among individuals with serious mental illness. METHODS: Association of delays in medical care with blood pressure, serum hemoglobin A1c (HbA1C), and lipids was assessed among patients at two inner-city community mental health centers. RESULTS: Of 271 participants, 62% reported delays in seeking general medical care due to attitudinal and financial barriers. Care delay was associated with abnormalities in measured blood pressure (adjusted odds ratio [AOR]=2.14, p=.029) and HbA1c (AOR=3.18, p=.026). Care delay was not associated with abnormalities in lipid profiles. CONCLUSIONS: This study found that delays in seeking general medical care are common and are associated with clinical markers linked with common medical conditions. The results may help to explain the elevated morbidity and mortality associated with serious mental illness.

Antigliadin Antibodies (AGA IgG) Are Related to Neurochemistry in Schizophrenia.

Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood-brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows the quantification of certain neurochemicals in vivo that may proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine). The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine; GPC + PC) in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30%) had positive AGA IgG (≥20 U) similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007) and GPC + PC (r = 0.36, p = 0.045) with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain inflammation as measured by MRS in schizophrenia.