S296 Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384

service structure and delivery. It remains important to evaluate whether

individual policies are applicable within a local context. Limitations of this

study are that the comparison is with a historical cohort and is confined to

in-patient costs. Further research in this area is required with contempora-

neous control groups. More detailed methods to capture community costs

will reveal to what extent the savings in admission costs are balanced by

increased costs of community service provision.

Poster #T19

ANIMAL MODELS OF SCHIZOPHRENIA SYMPTOMS: POLYDIPSIA

FOLLOWING SUBCHRONIC MK-801, POST-WEANING SOCIAL ISOLATION

OR AMPHETAMINE SENSITIZATION IN RATS

Richard J. Beninger1,2, Emily R. Hawken2

1Depts. Psychology and Psychiatry; 2Queen’s University, Kingston, Canada

Background: Polydipsia is observed in up to 20% of chronic psychiatric pa-

tients with a majority of cases (80%) occurring in patients with schizophre-

nia. Animal models of schizophrenia symptoms including subchronic treat-

ment with a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist,

post-weaning social isolation and amphetamine sensitization reproduce a

number of symptoms including working memory impairments, increased

locomotor responses to amphetamine and impaired sensory-motor gating.

We evaluated the hypothesis that these models will reproduce polydipsia.

Methods: Young adult male rats were injected twice daily with the NMDA

receptor antagonist MK-801 (0.5 mg/kg) or its vehicle for 7 days and then

given a 4-day washout period. Post-weaning rats (age 21 days) were housed

alone (socially isolated) or in groups of 4 for 6 weeks. Young adult male rats

were injected with amphetamine (1.5 mg/kg) or its vehicle once daily for 5

days and given a 4-week withdrawal period. All rats were then restricted

to food access for 2 hr per day. Drinking behavior was evaluated in 21 daily

2-hr sessions using the schedule-induced polydipsia (SIP) procedure in an

operant chamber outfitted with a food hopper and a drinking spout; food

pellets (45 mg) were presented according to a fixed time 1-min schedule

during these sessions. The dependent variable was amount drunk.

Results: As reported previously by a number of researchers, animals

exposed to the SIP procedure developed polydipsia over the course of

testing. Similar animals given the food pellets all at once in a bowl at

the beginning of the 2-hr test session did not develop polydipsia. Animals

previously treated subchronically with MK-801, socially isolated during

the post-waning period or previously sensitized to amphetamine devel-

oped polydipsia but drank significantly more than their respective control

groups. These treatments were not associated with a change in amount

drunk in the home cage. Rats tended to spend most time at the drinking

spout immediately following pellet presentations.

Discussion: Results supported previous findings showing that exposing

food-restricted rats to intermittent food presentations at regular intervals

leads to the development of excessive drinking. Providing the same amount

of food all at once has no similar effect. There was remarkable conver-

gence of effects of the three animal models of schizophrenia symptoms

on polydipsia. Subchronic NMDA receptor blockade, post-weaning social

isolation and amphetamine sensitization all led to significantly greater

polydipsia than observed in the respective control groups. The mechanisms

underlying this effect remain to be determined. Some evidence relates

hippocampal dysfunction to polydipsia. Subchronic NMDA receptor an-

tagonist treatment has been shown to affect hippocampal GABA neurons

and post-weaning social isolation alters markers of GABA function in the

hippocampus, providing a possible link. These treatments also lead to

augmented dopaminergic neurotransmission as does amphetamine sensi-

tization, implicating dopamine in the mechanism. It has been suggested

that hyperdopaminergia in schizophrenia may be secondary to changes

in hippocampal GABA function. The present results provide convergent

evidence from three different animal models of schizophrenia symptoms

suggesting that polydipsia may result from the same neuropathologies that

lead to other schizophrenia symptoms. (Funded by a grant from the Ontario

Mental Health Foundation)

Poster #T20

THE ASSOCIATION BETWEEN INFECTIONS AND GENERAL COGNITIVE

ABILITY IN YOUNG MEN – A DANISH NATIONWIDE STUDY

Michael E. Benros1,2, Holger Sørensen3, Philip Nielsen4,

Merete Nordentoft5, Preben Bo Mortensen4, Liselotte Petersen4

1Mental Health Centre Copenhagen, Copenhagen University Hospital; 2Mental

Health Centre of Copenhagen, Copenhagen University Hospital and National

Centre for Register-based Research, Aarhus University; 3Mental Health Centre

of Copenhagen, Copenhagen University Hospital; 4National Centre for

Register-based Research, Aarhus University; 5Mental Health Center

Copenhagen

Background: Infections and inflammation have been shown to increase the

risk of mental disorders with affected cognition. Furthermore, infections

and immune components might also affect the developing brain and influ-

ence the cognitive ability in people without mental disorders. However, no

large-scale study has previously investigated the effect of infections on the

general cognitive ability in the general population.

Methods: Danish nationwide registers were linked to establish a cohort of

all 161,696 male conscripts that were tested for cognitive ability during the

years 2006-2012. Severe infections requiring hospitalization was the expo-

sure and draft board general cognitive ability was the dependent variable,

which was based on logical, verbal, numerical and spatial reasoning at a

mean age of 19.4 years with converted test scores to a mean of 100.00.

Results: A prior infection was associated with significantly lower cognitive

ability by a mean of 1.76 (95%CI: -1.92 to -1.61). The cognitive ability was

affected the most with the temporal proximity of the last infection and with

severity measured by days of admission. The cognitive ability decreased by

the amount of infections exposed to, where the highest mean differences

were found for ≥10 hospital contacts for infections (Mean: -5.54; 95%CI:

-7.11 to -3.98), and for ≥5 different types of infections (Mean: -9.44; 95%CI:

-12.6 to -6.26).

Discussion: Independent of a wide range of possible confounders, signifi-

cant associations between infections and cognitive ability were observed.

Infections or related immune responses might directly affect the cognitive

ability; however, associated heritable and environmental factors might also

account for the decreased cognitive ability.

Poster #T21

MATERNAL SMOKING DURING PREGNANCY AND SYMPTOM SEVERITY

AMONG OFFSPRING DURING THEIR FIRST EPISODE OF PSYCHOSIS

Francesco Bernardini1, Michael T. Compton2

1School of Psychiatry – University of Perugia, Perugia, Italy; 2Lenox Hill

Hospital

Background: Maternal smoking during pregnancy is associated with a

number of negative effects for the fetus and later the child, including

adverse neurodevelopmental and behavioral outcomes. Prenatal exposure

to tobacco smoke has been reported to be associated with an increased

incidence of attention-deficit/hyperactivity disorder, conduct disorder, and

reduced cognitive ability. In animal studies, long-term prenatal nicotine

exposure alters the development of a wide spectrum of neuronal systems,

all of which potentially could induce vulnerability to schizophrenia. Epi-

demiological and clinical studies indicate that prenatal tobacco exposure is

associated with various psychiatric symptoms, including psychotic symp-

toms, as well as the development of psychiatric disorders. Fetal exposure

to maternal smoking during pregnancy might also impact illness manifes-

tation among individuals with schizophrenia. Recent findings suggest that

prenatal exposure to tobacco smoke increases risk for later schizophre-

nia and is associated with the development of more prominent negative

symptoms.

Methods: We examined associations between maternal smoking during

pregnancy, using retrospective data provided by mothers, and symptom

severity of first-episode psychosis patients, rated by trained research staff

using the Positive and Negative Syndrome Scale (PANSS). Among 93 first-

episode patients, 19 (20.4%) had been exposed to prenatal tobacco smoke

according to mothers’ reports. The average number of cigarettes smoked

per month during pregnancy was 113.7 (equating to 5.7 packs per month,

or 1.3 packs per week).