Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S25

EARLY-LIFE EXPOSURE TO EPSTEIN BARR VIRUS, CHILDHOOD IQ AND

THE RISK OF PSYCHOTIC EXPERIENCES IN THE ALSPAC BIRTH COHORT

Golam Khandaker1, Jan Stochl1, Stanley Zammit2, Glyn Lewis3,

Peter Jones4

1University of Cambridge; 2University of Cardiff, UK; 3UCL; 4Department

Psychiatry, University of Cambridge

Background: Early-life infection is associated with the increased risk of

adult psychotic illness. Cross-sectional studies have reported increased

prevalence of Epstein Barr virus (EBV), a member of the herpes fam-

ily in schizophrenia; also, a possible role of herpes virus in cognitive

dysfunction in schizophrenia and healthy controls. Using data from the

general population-based Avon Longitudinal Study of Parents and Children

(ALSPAC) birth cohort, we report a longitudinal study of the association

between early-life exposure to EBV, childhood IQ and the risk of psychotic

experiences (PE) in early adolescence.

Methods: Serum IgG antibodies to EBV were measured at age 4 years in a

representative subsample of the cohort (N=530). The assessments for IQ at

age 9 years and PE at age 13 years were attended by 392 and 366 of these

individuals, respectively. Logistic regression calculated odds ratios (OR) for

PE in the EBV-exposed compared with the unexposed individuals. Mean IQ

scores were compared between these exposure groups; mediating effects of

IQ on the EBV-PE association was examined. Potential confounders included

age, gender, ethnicity, social class, household crowding, and depression at

the time of assessment of PE.

Results: About 25% of the sample was exposed to EBV at age 4 years. EBV

exposure was associated with a five-fold risk of PE; OR for definite PE

5.37 (95% CI 1.71- 16.87), which remained significant after adjusting for

confounders. EBV-exposed individuals performed worse on all measures of

IQ; mean difference in full-scale IQ between EBV-exposed and unexposed

groups was 4.55 (95% CI 0.88- 8.23); however, this was explained by

socio-demographic differences.

Conclusions: Early-life exposure to EBV is associated with the increased

risk of PE in early adolescence; an association not mediated by IQ. Thus, CNS

alterations arising from early-life infections that lead to an increased risk of

psychotic outcomes may be independent of childhood cognitive deficit as

captured by IQ test. Scientific 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 BIPOLAR

DISORDER 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. Schaefer5

1Columbia 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 Infectious

Diseases and Immunology, Department of Medicine, University of

Massachusetts Medical School, Worcester, MA; 5Division of Research, Kaiser

Permanente, Oakland, CA

Background: Elevated maternal antibody to influenza has been associated

previously with schizophrenia. In order to assess the diagnostic specificity

of the association, we examined whether serologically documented mater-

nal influenza antibody is related to bipolar disorder (BD) in adult offspring

from the same birth cohort as in the study of schizophrenia.

Methods: Cases with BD were followed up by linkages between the Child

Health and Development Study and the Kaiser Permanente Medical Care

Plan (KPNC) and Alameda County Behavioral Health Care Services databases,

as well as by a large survey of the cohort. Potential cases were diagnosed

with the SCID for DSM-IV-TR by consensus of three experienced psychiatric

diagnosticians supplemented by medical records. Maternal archived serum

specimens 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 assayed

for influenza antibody by hemagglutination inhibition. Conditional logistic

regression analyses were conducted.

Results: Serologically documented influenza at any time during pregnancy

was significantly increased in cases with BD with psychotic features (38.9%)

compared to controls (18.1%) (OR=5.03, 95% CI=1.38–18.4, p=0.015). There

was no relationship between maternal influenza and all BD cases nor

among BD cases without psychotic features.

Conclusion: These findings suggest that second trimester exposure to in-

fluenza may be a risk factor for BD with psychotic features in offspring,

suggesting that this infection may not be specific to schizophrenia among

major psychiatric disorders.

FETAL AND CHILDHOOD INFECTIONS AND LATER RISK OF DEVELOPING

PSYCHOSES; IN SEARCH OF POSSIBLE UNDERLYING MECHANISMS BY

COMBINING DIFFERENT RESEARCH DISCIPLINES

Åsa Blomström1, Håkan Karlsson2, Anna Svensson3, Thomas Frisell4,

Henrik Dahl3, Cecilia Magnusson3, Renee M. Gardner3, Susanne Wicks3,

Christina Dalman3

1Public Health Sciences, Karolinska Institute; 2Department of Neuroscience,

Karolinska Institutet, Stockholm, Sweden; 3Department of Public Health

Sciences, Karolinska Institutet, Stockholm, Sweden; 4Department of Medical

Epidemiology 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 infection

during pregnancy has been pointed out as a risk factor for psychosis in

offspring. However, brain development proceeds continuously throughout

childhood. Nevertheless, the effect of infection during these ages is insuf-

ficiently examined. In this study, all individuals born in Sweden 1973-85,

(N=1,172,879) were followed up regarding first time in-patient care with

non-affective psychosis from 14 years until 2006, (N=4 638), and on so-

matic inpatient care with a diagnosis of infection during childhood (0–13

years). Hazard ratios (HR) of non-affective psychosis were calculated with

Cox regression. Potential confounders included differences in sex, socioeco-

nomic status, family history of psychosis and hospital admissions involving

non-infectious and non-psychiatric care. A small but significant association

was observed between hospital admissions with any infection throughout

childhood (0–13 years) and a later diagnosis of non-affective psychosis,

HR=1.10 (95% CI 1.03–1.18). This association was driven by bacterial infec-

tion, HR=1.23 (95% CI 1.08–1.40). More specifically, bacterial infection and

CNS-infection during preadolescence (10–13 years) conferred the strongest

risk, HR 1.59 (95% CI 1.22–2.08), and HR 1.96 (95% CI 1.06–3.65) respec-

tively. Patients with non-affective psychosis had more admissions with

infection during childhood; HR 1.37 (95% CI 1.06–1.78) for ≥4 admissions,

after adjusting for confounders. Preadolescence appears to be a vulnerable

age period to acquire an infection, and bacterial infections the most severe

in relation to psychosis development. However, the present findings could

also indicate an increased susceptibility to hospital admission for infections

among children who will later develop psychosis due to social or famil-

ial/genetic factors. In fact, adjusting for admission with other diagnoses

and parental psychiatric disease had an attenuating effect on the estimates.

The underlying mechanisms are unknown but inflammatory processes may

be 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 deficits in the innate immune defense of

these newborns, which potentially increase either their risk of contracting

infections or the severity of contracted infections. The pathogenesis how-

ever remains obscure but can potentially involve direct effect of infectious

agents and/or indirect effects of maternal immune activation (MIA) modu-

lating the development during fetal life and childhood, including the innate

immune 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. Maternal

exposure status of Toxoplasma gondii (T. gondii), cytomegalovirus (CMV),

and Herpes simplex virus type 1 (HSV-1) and -2 (HSV-2) was known for

all participants. Levels of 9 APPs in archived neonatal dried blood samples

from these individuals were determined. Controls exposed to T. gondii and

CMV had significantly higher levels of all APPs compared to unexposed

controls. Among cases however the levels remained low irrespective of

exposure status. Maternal exposure to HSV-1 or -2 did not affect APP levels

in neither group. Thus it seems as specific maternal infections alter the

child’s innate immune response and as psychosis patients have deficiencies

in the response which could render the child vulnerable to later infections.