SS-05-01

A. Hofer. Innsbruck University, Innsbruck, Austria

SS-05-02

Neuroimaging in people vulnerable to psychosis

P. McGuire. Institute of Psychiatry, King', London, United Kingdom

While genetic factors are clearly important in determining the risk of psychosis, many of those at high risk have no family history of psychosis and in these individuals environmental factors appear to be more relevant. Subjects with prodromal symptoms (meeting PACE criteria) were recruited locally and studied using a 1.5T MRI camera. Most came from ethnic minority groups and had no family history of psychosis. MRI, DTI and functional MRI data were acquired from subjects with prodromal symptoms, healthy volunteers and patients with first episode psychosis. Images were processed using non parametric methods. Compared to controls, subjects with prodromal symptoms showed qualitatively similar differences to those seen in patients with first episode psychosis. However the severity of these differences was less marked in the at risk subjects. Changes in the structure and function of the brain are evident in people with prodromal symptoms and these may be particularly related to environmental risk factors for psychosis.

SS-05-03

R. Kalm. University Medical Center, Ga Utrecht, Netherlands

SS-05-04

Brain dopamine dl receptors in monozygotic and dizygotic twin pairs discordant for schizophrenia

J. Hietala. Turku University & Turku PET C, Turku, Finland

Objective: Schizophrenia has a heritability of about 80% but the detailed molecular genetic basis of the disorder has remained elusive. We hypothetized that altered dopamine transmission is related to psychosis susceptibility and started a series of neuroimaging studies on the dopamine system in monozygotic and dizygotic twin pairs discordant for schizophrenia.

Methods: We have previously shown that caudate dopamine D2 receptor upregulation is related to genetic risk for schizophrenia using this twin design. Higher dopamine D2 receptor density in caudate was also associated with poorer performance on cognitive tasks involving cortico-striatal pathways (Hirvonen et al, Arch Gen Psychiatry, in press.We now report DI receptor binding results on the same twin sample.D1 receptor density in the brain was measured with [11C]SCH 23390 and 3D PET.

Results: High D1 receptor density in heteromodal association cortex (angular and supramarginal gyri), superior temporal gyrus and medial prefrontal cortex was associated with increased genetic risk for schizophrenia (unaffected MZ> unaffected DZ>control twins). High D 1 receptor binding was also associated with impaired neurocognitive performance.

Conclusion: Our findings suggest that cortical dopamine dysregulation is associated to psychosis vulnerability. The results provide also theoretical rationales for early pharmacological intervention strategies in high risk prodromal subjects.

SS-05-05

What is genetically mediated in subjects at high genetic risk?

S. Lawrie. Division of Psychiatry University of Edinburgh, Edinburgh, United Kingdom

Objective: We have found several clinical, cognitive and imaging measures which differ between subjects at high genetic risk of schizophrenia and healthy controls, but these presumably reflect both genetic effects and gene-environment interactions.

Methods: We have examined which of these variables are associated with two specific measures of genetic liability to schizophrenia- a quantitative measure developed by Pak Sham and simple categorical measure according to the presence of affected first degree relatives or not.

Results: Statistically significant associations include performance on three cognitive tests (Rivermead story delayed recall, VF animals, Hayling A); the volumes of the pre-frontal lobes and thalamus; and fronto-frontal functional disconnectivity on fMRI across distinct sentence completion, encoding and retrieval cognitive tasks. Notable non-significant associations include psychotic symptoms, the volumes of the medial temporal lobes; obstetric complications, minor physical anomalies and neurological soft signs. None of the apparently genetically mediated measures were however predictive of psychosis within the high risk cohort.

Conclusion: Overall, the results suggest that some abnormalities of brain structure and function in high risk subjects are genetically mediated, but that others may only become apparent around the time of psychosis onset for as yet unclear reasons.