Andrew N. Berrett

Association between latent toxoplasmosis and cognition in adults: a cross-sectional study

Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.

Infectious disease burden and cognitive function in young to middle-aged adults

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults.

Folate and Inflammatory Markers Moderate the Association Between Helicobacter pylori Exposure and Cognitive Function in US Adults

Helicobacter pylori (H. pylori) infection is associated with cognitive deficits in humans, an association potentially mediated or moderated by folate concentration or inflammation.

No association between current depression and latent toxoplasmosis in adults

Changes in behaviour and cognition have been associated with latent infection from the apicomplexan protozoan Toxoplasma gondii (Nicolle et Manceaux, 1908) in both animal and human studies. Further, neuropsychiatric disorders such as schizophrenia have also been associated with latent toxoplasmosis. Previously, we found no association between T. gondii immunoglobulin G antibody (IgG) seropositivity and depression in human adults between the ages of 20 and 39 years (n = 1 846) in a sample representative of the United States collected by the Centers for Disease Control as part of a National Health and Nutrition Examination Survey (NHANES) from three datasets collected between 1999-2004. In the present study, we used NHANES data collected between 2009 and 2012 that included subjects aged 20 to 80 years (n = 5 487) and used the Patient Health Questionnaire 9 (PHQ-9) to assess depression with the overall aim of testing the stability of the results of the prior study. In the current study, the seroprevalence of T. gondii was 13%. The percentage of subjects reporting clinical levels of depression assessed with the PHQ-9 was 8%. As before, we found no association between T. gondii IgG seroprevalence and depression (OR = 1.01, 95% CI = 0.81-1.25; p = 0.944) while controlling for sex, educational attainment, race-ethnicity, age, poverty-to-income ratio and cigarette smoking. We also found no positive associations between anti-T. gondii antibody titre and depression (OR = 1.00, 95% CI = 0.96-1.06; p = 0.868). Moreover, we found no association between T. gondii seroprevalence or antibody titre and suicidal ideation (seroprevalence: OR = 1.22, 95% CI = .85-1.75; p = 0.277, titre: OR = 1.05, 95% CI = 0.98-1.14; p = 0.177). Defining depression to also include subjects currently taking antidepressant medication even with non-elevated questionnaires did not find evidence of a positive association between latent toxoplasmosis and depression. In the present study, neither T. gondii seroprevalence nor anti-T. gondii antibody titre was positively associated with depression or suicidal ideation among subjects aged 20 to 80 years.

Toxoplasma Gondii Moderates the Association between Multiple Folate-Cycle Factors and Cognitive Function in U.S. Adults

Toxoplasma gondii (T. gondii) is a microscopic, apicomplexan parasite that can infect muscle or neural tissue, including the brain, in humans. While T. gondii infection has been associated with changes in mood, behavior, and cognition, the mechanism remains unclear. Recent evidence suggests that T. gondii may harvest folate from host neural cells. Reduced folate availability is associated with an increased risk of neurodevelopmental disorders, neurodegenerative diseases, and cognitive decline. We hypothesized that impairment in cognitive functioning in subjects seropositive for T. gondii might be associated with a reduction of folate availability in neural cells. We analyzed data from the third National Health and Nutrition Examination Survey to determine the associations between T. gondii infection, multiple folate-cycle factors, and three tests of cognitive functioning in U.S. adults aged 20 to 59 years. In these analyses, T. gondii moderated the associations of folate, vitamin B-12, and homocysteine with performance on the Serial Digit Learning task, a measure of learning and memory, as well as the association of folate with reaction time. The results of this study suggest that T. gondii might affect brain levels of folate and/or vitamin B-12 enough to affect cognitive functioning.

Toxocara Seroprevalence and Associated Risk Factors in the United States

Caused by the parasitic nematodes Toxocara canis and cati, toxocariasis in humans can result in covert toxocariasis, ocular toxocariasis, visceral larval migrans, and neurotoxocariasis. A common infection, toxocariasis exposure varies widely within and between countries, with a previous estimate of Toxocara seroprevalence using data from 1988 to 1994 in the United States of approximately 13%. Age, poverty, sex, educational attainment, ethnicity, and region have been associated with Toxocara seroprevalence. In this study, we sought to determine the seroprevalence of and factors associated with Toxocara seropositivity in the United States using data from the National Health and Nutrition Examination Survey from 2011 to 2014 to provide a more recent estimate of Toxocara seroprevalence in the United States. We found an overall Toxocara seroprevalence of 5.1%. Increasing age, male sex, low educational attainment, low income, and immigration status each was associated with Toxocara seropositivity. Mexican Americans had reduced odds of exposure. These findings show that exposure to Toxocara continues in the United States and that several demographic factors influence the risk of exposure.

Association between virus exposure and depression in US adults

Mood disorders are common mental illnesses. Among the factors associated with major depression are exposures to infectious diseases including hepatitis C, influenza, varicella-zoster, and herpes viruses. In this study, we sought to evaluate further associations between viral exposure and depression. From the US Center for Disease Controls National Health and Nutrition Examination Survey, we obtained data about depression status, antidepressant use, exposure to hepatitis A, hepatitis B, herpes simplex virus type 1, herpes simplex virus type 2, human immunodeficiency virus, and cytomegalovirus, and sociodemographic variables and evaluated associations between depression and viral exposure in adjusted multivariable models. Herpes simplex virus type 2 was associated with an increased risk of depression, whereas hepatitis A, hepatitis B, and herpes simplex virus type 1 were not. Higher cytomegalovirus antibody levels were associated with depression in subjects seropositive for cytomegalovirus. In conclusion, exposure to herpes simplex virus type 2 and possibly cytomegalovirus are associated with depression in an adult US sample.

Helicobacter pylori moderates the association between 5-MTHF concentration and cognitive function in older adults

Objective To explore potential interactions between folate-cycle factors and Helicobacter pylori seropositivity in the prediction of cognitive function. Methods We used data obtained from the 1999–2000 continuous National Health and Nutrition Examination Survey produced by the United States’ Centers for Disease Control and Prevention. Using Ordinary Least Squares regression, we tested for associations between multiple folate-cycle factors, Helicobacter pylori seropositivity, and cognitive function assessed by the digit symbol coding subtest of the Wechsler Adult Intelligence Scale-III. We then tested for interactions between each of the folate-cycle factors and Helicobacter pylori in the prediction of cognitive function. Results Although Helicobacter pylori seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not associated with performance on the digit symbol coding task, Helicobacter pylori seropositivity interacted with 5-methyltetrahydrofolate concentration to predict performance on the digit symbol coding task. The Helicobacter pylori seropositive group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate concentration decreased. Conclusion The interaction between Helicobacter pylori seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might impair aspects of cognitive function.

Toxoplasma gondii seropositivity and substance use in US adults

The intracellular parasite Toxoplasma gondii (Nicolle et Manceaux, 1908) infects humans resulting in acute toxoplasmosis, an infection that in immunocompetent people is typically mild but results in persistent latent toxoplasmosis. In that T. gondii appears to affect dopamine synthesis and because addicting drugs affect midbrain dopamine transmission, latent toxoplasmosis could influence substance use. Using both the third and continuous National Health and Nutrition Examination Surveys from the US Centers for Disease Control and Prevention, we used logistic regression to test for associations between T. gondii seropositivity and subject self-report of having ever used tobacco, alcohol, marijuana, cocaine, heroin, or methamphetamine. In the third NHANES dataset, which included data for tobacco, alcohol, marijuana and cocaine, T. gondii seropositivity was associated with a reduced likelihood of self-reported marijuana (OR = 0.71 [95% CI: 0.58; 0.87]; p = 0.001) and cocaine use (OR = 0.72 [95% CI: 0.56; 0.91]; p = 0.006). In the continuous National Health and Nutrition Examination Surveys dataset, which included data for all six substances, T. gondii seropositivity was associated with a reduced likelihood of self-reported tobacco (OR = 0.87 [95% CI: 0.76; 1.00]; p = 0.044), marijuana (OR = 0.60 [95% CI: 0.50; 0.72]; p < 0.001), heroin (OR = 0.60 [95% CI: 0.42; 0.85]; p = 0.005) and methamphetamine use (OR = 0.54 [95% CI: 0.38; 0.77]; p = 0.001). We observed interactions between sex and T. gondii seropositivity in the prediction of self-reported use of tobacco and alcohol. Further, T. gondii seropositivity appeared to remove the protective effect of education and economic status against self-reported cigarette smoking. These findings suggest that T. gondii seropositivity may be inversely associated with some but not all types of substance use in US adults.

Association between infection burden and adult height

HighlightsAn infection‐burden index predicted adult height in the United States.Sex and ethnic background moderated the association between height and infection.Toxocara, cytomegalovirus, and hepatitis A each individually predicted height. ABSTRACT Although highly heritable, adult height is also associated with numerous environmental factors, including exposure to infection. Particularly in developing regions of the world, infection burden appears to slow growth during childhood. Using a large database representative of the US population, we examined associations between adult height and leg length and an infection‐burden index based on past exposure to Toxocara species, Toxoplasmosis gondii, cytomegalovirus, hepatitis A, hepatitis B, hepatitis C, herpes simplex virus 1, and herpes simplex virus 2. In models controlled for age, sex, educational attainment, socioeconomic status, and race‐ethnicity, we found that the infection‐burden index predicted height (&bgr; = −0.10 [95% CI: −0.15, −0.05], p .001<0.001) but not leg length (&bgr; = −0.04 [95% CI: −0.12, 0.04], p = 0.357). Both sex and race‐ethnicity moderated this association. In addition, exposures to Toxocara species, cytomegalovirus, and hepatitis A were each individually associated with reduced height and reduced leg length. While associations between growth and infection have been found principally in children in developing regions of the world, our findings suggest that the effects of infection on height may persist into adulthood even in developed nations.