Maternal Exposure to Herpes Simplex Virus and Risk of Psychosis Among Adult Offspring
ABSTRACT Viral exposure during gestation is thought to be a risk factor for schizophrenia. Previous studies have indicated that prenatal exposure to herpes simplex virus type 2 (HSV-2) may be a risk for the subsequent development of schizophrenia in some populations. In this investigation, we tested a large and diverse population to assess the risk of psychoses among offspring of mothers with serological evidence of HSV-2 infection.
We conducted a nested case-control study of 200 adults with psychoses and 554 matched control subjects (matched for city and date of birth, race/ethnicity, gender, and parent history of treatment for mental disorder) from three cohorts of the Collaborative Perinatal Project (Boston, Providence, and Philadelphia). We analyzed stored serum samples that had been obtained from these mothers at the end of pregnancy for antibodies directed at HSV-2, using type-specific solid-phase enzyme immunoassay techniques.
Offspring of mothers with serologic evidence of HSV-2 infection were at significantly increased risk for the development of psychoses (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.3). This risk was particularly elevated among women with high rates of sexual activity during pregnancy (OR = 2.6; 95% CI = 1.4-4.6).
Maternal exposure to herpes simplex virus type 2 is associated with an increased risk for psychoses among adult offspring. These results are consistent with a general model of risk resulting from enhanced maternal immune activation during pregnancy.
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ABSTRACT: Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments. A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent. The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 05/2012; 69(9):757-66. DOI:10.2146/ajhp110271 · 2.21 Impact Factor
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ABSTRACT: Schizophrenia and affective psychoses are debilitating disorders that together affect 2%-3% of the adult population. Approximately 50%-70% of the offspring of parents with schizophrenia manifest a range of observable difficulties including socioemotional, cognitive, neuromotor, speech-language problems, and psychopathology, and roughly 10% will develop psychosis. Despite the voluminous work on premorbid vulnerabilities to psychosis, especially on schizophrenia, the work on premorbid intervention approaches is scarce. While later interventions during the clinical high-risk (CHR) phase of psychosis, characterized primarily by attenuated positive symptoms, are promising, the CHR period is a relatively late phase of developmental derailment. This article reviews and proposes potential targets for psychosocial interventions during the premorbid period, complementing biological interventions described by others in this Special Theme issue. Beginning with pregnancy, parents with psychoses may benefit from enhanced prenatal care, social support, parenting skills, reduction of symptoms, and programs that are family-centered. For children at risk, we propose preemptive early intervention and cognitive remediation. Empirical research is needed to evaluate these interventions for parents and determine whether interventions for parents and children positively influence the developmental course of the offspring. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: email@example.com.Schizophrenia Bulletin 04/2015; DOI:10.1093/schbul/sbv047 · 8.61 Impact Factor
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ABSTRACT: The authors analyzed archival dried blood spots obtained from newborns to assess whether levels of immunoglobulin G (IgG) directed at dietary antigens were associated with a later diagnosis of a nonaffective psychotic disorder. The study population consisted of individuals born in Sweden between 1975 and 1985 with verified register-based diagnoses of nonaffective psychoses made between 1987 and 2003 and comparison subjects matched on sex, date of birth, birth hospital, and municipality. A total of 211 case subjects and 553 comparison subjects consented to participate in the study. Data on factors associated with maternal status, pregnancy, and delivery were extracted from the Swedish Medical Birth Register. Levels of IgG directed at gliadin (a component of gluten) and casein (a milk protein) were analyzed in eluates from dried blood spots by enzyme-linked immunosorbent assay. Odds ratios were calculated for levels of IgG directed at gliadin or casein for nonaffective psychosis. Levels of anti-gliadin IgG (but not anti-casein IgG) above the 90th percentile of levels observed among comparison subjects were associated with nonaffective psychosis (odds ratio=1.7, 95% CI=1.1-2.8). This association was not confounded by differences in maternal age, immigrant status, or mode of delivery. Similarly, gestational age at birth, ponderal index, and birth weight were not related to maternal levels of anti-gliadin IgG. High levels of anti-gliadin IgG in the maternal circulation are associated with an elevated risk for the development of a nonaffective psychosis in offspring. Research is needed to identify the mechanisms underlying this association in order to develop preventive strategies.American Journal of Psychiatry 04/2012; 169(6):625-32. DOI:10.1176/appi.ajp.2012.11081197 · 13.56 Impact Factor