SEROLOGICALLY DOCUMENTED MATERNAL INFLUENZA AND BIPOLAR DISORDER IN ADULT OFFSPRING
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Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1S384 S25
EARLY-LIFE EXPOSURE TO EPSTEIN BARR VIRUS, CHILDHOOD IQ ANDTHE RISK OF PSYCHOTIC EXPERIENCES IN THE ALSPAC BIRTH COHORT
Golam Khandaker1, Jan Stochl1, Stanley Zammit2, Glyn Lewis3,Peter Jones41University of Cambridge; 2University of Cardiff, UK; 3UCL; 4DepartmentPsychiatry, University of Cambridge
Background: Early-life infection is associated with the increased risk ofadult psychotic illness. Cross-sectional studies have reported increasedprevalence of Epstein Barr virus (EBV), a member of the herpes fam-ily in schizophrenia; also, a possible role of herpes virus in cognitivedysfunction in schizophrenia and healthy controls. Using data from thegeneral population-based Avon Longitudinal Study of Parents and Children(ALSPAC) birth cohort, we report a longitudinal study of the associationbetween early-life exposure to EBV, childhood IQ and the risk of psychoticexperiences (PE) in early adolescence.Methods: Serum IgG antibodies to EBV were measured at age 4 years in arepresentative subsample of the cohort (N=530). The assessments for IQ atage 9 years and PE at age 13 years were attended by 392 and 366 of theseindividuals, respectively. Logistic regression calculated odds ratios (OR) forPE in the EBV-exposed compared with the unexposed individuals. Mean IQscores were compared between these exposure groups; mediating effects ofIQ on the EBV-PE association was examined. Potential confounders includedage, gender, ethnicity, social class, household crowding, and depression atthe time of assessment of PE.Results: About 25% of the sample was exposed to EBV at age 4 years. EBVexposure was associated with a ve-fold risk of PE; OR for denite PE5.37 (95% CI 1.71- 16.87), which remained signicant after adjusting forconfounders. EBV-exposed individuals performed worse on all measures ofIQ; mean difference in full-scale IQ between EBV-exposed and unexposedgroups was 4.55 (95% CI 0.88- 8.23); however, this was explained bysocio-demographic differences.Conclusions: Early-life exposure to EBV is associated with the increasedrisk of PE in early adolescence; an association not mediated by IQ. Thus, CNSalterations arising from early-life infections that lead to an increased risk ofpsychotic outcomes may be independent of childhood cognitive decit ascaptured by IQ test. Scientic endeavour to unravel the mechanisms under-lying the link between psychosis and early-life infection should, therefore,consider alternative pathways possibly immune and genetic.
SEROLOGICALLY DOCUMENTED MATERNAL INFLUENZA AND BIPOLARDISORDER IN ADULT OFFSPRING
Alan Brown1,2, Sarah E. Canetta3, Yuanyuan Bao3, Mary Dawn T. Co4,Francis A. Ennis4, John Cruz4, Masanori Terajima4, Ling Shen5,Christoph Kellendonk3, Catherine A. Schaefer51Columbia University Medical Center; 2New York State Psychiatric Institute;3Department of Psychiatry, Columbia University of Physicians and Surgeons,New York State Psychiatric Institute, New York, NY; 4Division of InfectiousDiseases and Immunology, Department of Medicine, University ofMassachusetts Medical School, Worcester, MA; 5Division of Research, KaiserPermanente, Oakland, CA
Background: Elevated maternal antibody to inuenza has been associatedpreviously with schizophrenia. In order to assess the diagnostic specicityof the association, we examined whether serologically documented mater-nal inuenza antibody is related to bipolar disorder (BD) in adult offspringfrom the same birth cohort as in the study of schizophrenia.Methods: Cases with BD were followed up by linkages between the ChildHealth and Development Study and the Kaiser Permanente Medical CarePlan (KPNC) and Alameda County Behavioral Health Care Services databases,as well as by a large survey of the cohort. Potential cases were diagnosedwith the SCID for DSM-IV-TR by consensus of three experienced psychiatricdiagnosticians supplemented by medical records. Maternal archived serumspecimens corresponding to cases with BD (N=85) and control (N=170)offspring matched 1:2 on date of birth, sex, availability of archived mater-nal sera, and KPNC membership/Alameda County residence were assayedfor inuenza antibody by hemagglutination inhibition. Conditional logisticregression analyses were conducted.Results: Serologically documented inuenza at any time during pregnancy
was signicantly increased in cases with BD with psychotic features (38.9%)compared to controls (18.1%) (OR=5.03, 95% CI=1.3818.4, p=0.015). Therewas no relationship between maternal inuenza and all BD cases noramong BD cases without psychotic features.Conclusion: These ndings suggest that second trimester exposure to in-uenza may be a risk factor for BD with psychotic features in offspring,suggesting that this infection may not be specic to schizophrenia amongmajor psychiatric disorders.
FETAL AND CHILDHOOD INFECTIONS AND LATER RISK OF DEVELOPINGPSYCHOSES; IN SEARCH OF POSSIBLE UNDERLYING MECHANISMS BYCOMBINING DIFFERENT RESEARCH DISCIPLINES
sa Blomstrm1, Hkan Karlsson2, Anna Svensson3, Thomas Frisell4,Henrik Dahl3, Cecilia Magnusson3, Renee M. Gardner3, Susanne Wicks3,Christina Dalman31Public Health Sciences, Karolinska Institute; 2Department of Neuroscience,Karolinska Institutet, Stockholm, Sweden; 3Department of Public HealthSciences, Karolinska Institutet, Stockholm, Sweden; 4Department of MedicalEpidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
At present, psychotic disorder is considered a neurodevelopmental disorder.As fetal life is a crucial period of brain development maternal infectionduring pregnancy has been pointed out as a risk factor for psychosis inoffspring. However, brain development proceeds continuously throughoutchildhood. Nevertheless, the effect of infection during these ages is insuf-ciently examined. In this study, all individuals born in Sweden 1973-85,(N=1,172,879) were followed up regarding rst time in-patient care withnon-affective psychosis from 14 years until 2006, (N=4 638), and on so-matic inpatient care with a diagnosis of infection during childhood (013years). Hazard ratios (HR) of non-affective psychosis were calculated withCox regression. Potential confounders included differences in sex, socioeco-nomic status, family history of psychosis and hospital admissions involvingnon-infectious and non-psychiatric care. A small but signicant associationwas observed between hospital admissions with any infection throughoutchildhood (013 years) and a later diagnosis of non-affective psychosis,HR=1.10 (95% CI 1.031.18). This association was driven by bacterial infec-tion, HR=1.23 (95% CI 1.081.40). More specically, bacterial infection andCNS-infection during preadolescence (1013 years) conferred the strongestrisk, HR 1.59 (95% CI 1.222.08), and HR 1.96 (95% CI 1.063.65) respec-tively. Patients with non-affective psychosis had more admissions withinfection during childhood; HR 1.37 (95% CI 1.061.78) for 4 admissions,after adjusting for confounders. Preadolescence appears to be a vulnerableage period to acquire an infection, and bacterial infections the most severein relation to psychosis development. However, the present ndings couldalso indicate an increased susceptibility to hospital admission for infectionsamong children who will later develop psychosis due to social or famil-ial/genetic factors. In fact, adjusting for admission with other diagnosesand parental psychiatric disease had an attenuating effect on the estimates.The underlying mechanisms are unknown but inammatory processes maybe involved. Recently we reported that neonates who will develop non-affective psychosis have lower levels of some acute phase proteins (APPs)as compared to controls indicating decits in the innate immune defense ofthese newborns, which potentially increase either their risk of contractinginfections or the severity of contracted infections. The pathogenesis how-ever remains obscure but can potentially involve direct effect of infectiousagents and/or indirect effects of maternal immune activation (MIA) modu-lating the development during fetal life and childhood, including the innateimmune system. We conducted a case control study including 198 indi-viduals born in Sweden 1975-85, diagnosed with non-affective psychoses,and 524 controls matched on sex, birth day, and birth hospital. Maternalexposure status of Toxoplasma gondii (T. gondii), cytomegalovirus (CMV),and Herpes simplex virus type 1 (HSV-1) and -2 (HSV-2) was known forall participants. Levels of 9 APPs in archived neonatal dried blood samplesfrom these individuals were determined. Controls exposed to T. gondii andCMV had signicantly higher levels of all APPs compared to unexposedcontrols. Among cases however the levels remained low irrespective ofexposure status. Maternal exposure to HSV-1 or -2 did not affect APP levelsin neither group. Thus it seems as specic maternal infections alter thechilds innate immune response and as psychosis patients have decienciesin the response which could render the child vulnerable to later infections.