William W. Eaton’s research while affiliated with Johns Hopkins University and other places

Purpose This study estimated risk of incident mental disorders in adulthood associated with both transient and persistent adolescent psychotic experiences (PEs). Methods A nested case-control design was used within the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort study which recruited expectant mothers from 1991–1992. Participants consisted of 8822 offspring of ALSPAC mothers who completed the Psychosis-like Symptoms Interview Questionnaire (PLIKSi-Q). PEs were assessed using the PLIKSi-Q. Depressive disorders were assessed using the Short Mood and Feelings Questionnaire (SMFQ), anxiety disorders using the General Anxiety Disorder Assessment and the Clinical Interview Schedule-Revised, and psychotic disorder using the PLIKSi. Risk of incident depressive disorder, GAD, psychotic disorder, and past-year suicide attempts were compared amongst participants who had ever versus never reported a PE and those who reported persistent versus transient PEs. Results Adolescent PEs were associated with increased risk for incident depressive disorder (adjusted hazard ratio (aHR) = 1.62, 95% CI = 1.42, 1.84), GAD (aHR 1.23, 95% CI = 1.03, 1.47), psychotic disorder (adjusted odds ratio (aOR) = 5.08, 95% CI = 2.02, 12.79), and past-year suicide attempts (aHR = 2.56, 95% CI = 1.97, 3.25). Persistent PEs were associated with increased risk for depressive disorder (aHR = 1.81, 95% CI = 1.55, 2.12), generalized anxiety disorder (aHR = 1.34, 95% CI = 1.07, 1.68), and psychotic disorder (aOR = 7.39, 95% CI = 2.43, 22.19) but not past-year suicide attempts. Conclusion Adolescent PEs are a risk factor for multiple mental disorders and suicide attempts, with persistent PEs conferring greater risk. Identifying interventions for adolescents who report PEs, particularly persistent PEs, could lessen the burden of multiple mental health disorders and suicide attempts.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Common infections (e.g., human herpesviruses and Toxoplasma gondii (TOX)), are associated with poor health outcomes, but less is known about associations between these infections and sleep. Due to, for instance, structural racism leading to policies and practices resulting in relative economic disadvantage and subsequently poorer living condition, sleep disturbances and common infections are more prevalent in minoritized populations. We investigated the cross-sectional associations of common infections (i.e., herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), and TOX with sleep disturbances, and determined whether these associations differed by race in 602 adults enrolled in the Baltimore Epidemiologic Catchment Area Study (mean age=59.0±12.8 years, 36.9% male, 35.6% minoritized). Participants donated a blood sample and were asked whether they had the insomnia symptoms “trouble falling asleep, staying asleep, or waking up too early” and reported on their habitual sleep duration. We measured immunoglobin G (IgG) antibodies to HSV-1, CMV, EBV, VZV, and TOX. After adjusting for sociodemographics, body mass index, comorbidities, household income, and household size, there were no associations between common infections and any sleep outcomes ; however, we observed interactions with race. Among White participants only, CMV seropositivity was associated with a lower odds of insomnia symptoms (OR = 0.26, 95% CI 0.10, 0.69) and TOX seropositivity was associated with shorter sleep duration (OR = 0.65, 95% CI 0.09, 1.21). Further research is needed to investigate mechanisms that may account for associations of CMV and TOX with sleep among White but not minoritized participants.

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.

This chapter reviews the basic principles of epidemiology and the most important results of epidemiologic research in the field of psychiatry over the past century. Critical concepts of measurement include the definition of prevalence and incidence, as assessed through systems of health surveillance, as well as population-based surveys. Essential concepts for organizing the results of psychiatric epidemiology include the burden of disorders, the life course framework, the study of risk factors, and the study of psychiatric and physical comorbidity. The chapter includes references to a wide range of psychiatric disorders, but the concepts of epidemiology are best represented by research on schizophrenia and depressive disorder, in part because these are the two most important disorders, and in part, because the literature is richest on these disorders.

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.

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-1β, 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.