Evidence that prenatal infection is a risk factor for brain and behaviour changes relevant to schizophrenia and autism

Poster PresentationMaternal infection during pregnancy increases risk of serious psychiatric disorders in the offspring such as schizophrenia and autism, in the offspring. Environmental influences are implicated in the development of ventriculomegaly in schizophrenia, the most consistent brain markers for schizophrenia in man. We hypothesized that maternal infection during pregnancy is an environmental risk factor for ventricular enlargement in offspring. To address this hypothesis we used an mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry (VBM) of in-vivo MRI data mapped cerebrospinal fluid across the whole brain. Manual region-of-interest tracing of lateral ventricles confirmed close overlap in ventriclar volumes extracted by each technique (Dice co-efficient = 0.93). We evaluated the behavioural and pharmacological impact of the prenatal exposure using the prepulse inhibition paradigm and an amphetamine challenge in the same mice. Maternal immune activation, in early but not late gestation, caused significant enlargement of lateral ventricles in adulthood. This early exposure disrupted prepulse inhibition and enhanced amphetamine sensitivity. Immune challenge in late gestation caused significant expansion of 4th ventricle volume and a lesser degree of amphetamine potentiation. Our findings lend direct support to the hypothesis that early prenatal immune activation exerts a more extensive neurodevelopmental impact in terms of schizophrenia-related brain and behavioral abnormalities compared with immunological insults taking place later in gestation. Such effects are potentially modifiable and deserve close attention in the context of the wider schizophrenia-autism spectrum.link_to_OA_fulltextThe 41st Meeting of the European Brain and Behaviour Society (EBBS) and the 23rd Meeting of the Hellenic Society for Neuroscience (HSfN), Rhodes Island, Greece, 13-18 September 2009. In Frontiers in Behavioral Neuroscience, 200