subjects matched for sex, age, and education level. Subjects readtwo word utterances: literal expressions, conventional and novelmetaphors, and unrelated word pairs. Subjects were asked to decidewhich kind of semantic relation exists between the two words(literal, metaphoric, or unrelated).Results: A direct comparison of the novel metaphors vs. theconventional metaphors revealed significantly stronger activity inthe right inferior frontal gyrus (IFG) in the controls group. Contrary tothe controls, the patients with schizophrenia activated IFG bilaterally,in addition to extended activation in the bilateral prefrontal cortex. Adirect comparison of the novel metaphors vs. the unrelated two-wordexpressions, both are unfamiliar expressions but only the novelmetaphors are meaningful, activated the left posterior superiortemporal sulcus to the same extent by both groups.Discussion: We conclude that schizophrenia patients appear todemonstrate loss of normal functional brain asymmetry, asreflected in diminished lateralization of language-related activationduring novel metaphoric processing in frontal region and overrecruitment of bilateral prefrontal regions. Furthermore, our resultssupport impairment in inhibition is a semantically irrelevantinformation in patients with schizophrenia.

doi:10.1016/j.schres.2010.02.620

Poster 126DIFFERENTIAL EPISTATIC EFFECTS BETWEEN DAAO AND G72 INHEALTHY CONTROLS AND PATIENTS WITH SCHIZOPHRENIA ANDBIPOLAR DISORDER

A. Mechelli, S.A. Papagni, D.P. Prata, J. Kambeitz, C.H. Fu, M.Picchioni, T. Toulopoulou, E. Bramon, M. Walshe, R.M. Murray, D.A.Collier, P. McGuirePsychosis Clinical Academic Group, Institute of Psychiatry King'sCollege London, London, United Kingdom

Background: Recent studies have identified DAAO and G72 asprobable susceptibility genes for schizophrenia and bipolardisorder. Both genes modulate glutamate neurotransmission,which is thought to be altered in schizophrenia and bipolardisorder. In addition, the two genes have been shown to interactwith each other at molecular level using in vitro transcription. Atpresent, however, little is known about how these genes may affectbrain function to increase vulnerability to these disorders. Thepresent investigation examined the impact of DAAO and G72genotypes on brain function in patients with schizophrenia,patients with bipolar I disorder and healthy volunteers. We testedthe hypothesis that the two genes would show an epistatic effecton brain function. In addition, based of recent studies showingevidence of a diagnosis-specific pattern of gene action, wehypothesised that epistatic effects between DAAO and G72 woulddiffer between controls and patients.Methods: We used functional magnetic resonance imaging tomeasure brain responses during a verbal fluency task in a totalof 120 subjects comprising 40 patients with schizophrenia,32 patients with bipolar disorder and 48 clinically healthy volun-teers. After pre-processing the data, we used statistical para-metric mapping (SPM) to estimate, for each diagnostic category,the effects of DAAO rs2111902 and G72 rs746187 genotypeand their interaction on brain function. Statistical inferenceswere made at p<0.05 after family-wise error (FWE) correctionfor multiple comparisons.Results: The SPM analysis revealed a diagnosis x DAAO x G72interaction in the right middle temporal gyrus (x=60 y=-12z=-12; z-score: 5.32; p<0.001 after FWE correction). In this

region, the A allele for G72 was associated with greater activationthan the G allele for G72 in individuals who were A homozygotefor DAAO but not in those who carried one or two copies of theC allele for DAAO; this epistatic effect was evident in patientswith bipolar disorder and schizophrenia, but was almost absentin healthy controls. There were no epistatic effects expressedconsistently across all three diagnostic groups.Discussion: These data demonstrate, for the first time, thatthe DAAO and G72 genes interact non-additively to modulatecortical function during executive processing in a middletemporal region which has been implicated in psychosis inprevious studies. In addition, the nature of this interactionappears to be different in patients relative to healthy controls,with significantly stronger epistatic effects in the former thanthe latter. Diagnosis-specific epistatic effects may reflect thealteration in glutamate function associated with the disordersand suggest that future genetic studies would benefit from as-sessing the DAAO and G72 genotypes together rather than eitherin isolation.

doi:10.1016/j.schres.2010.02.621

Poster 127EXPLORING THE NEURAL BASIS OF GAZE PERCEPTION ERRORS INSCHIZOPHRENIA

Mahesh Menon1,2, Sofia Raitsin2, Ariel Graff1,2, Christine Hooker3,Shitij Kapur1,41Centre for Addiction & Mental Health, Toronto, ON, Canada;2University of Toronto, Toronto, ON, Canada; 3Harvard University,Cambridge, MA, USA; 4Institute of Psychiatry, London, United Kingdom

Background: Previous research has suggested that patients withschizophrenia might show a self-referential bias in judging thedirection of eye gaze and are more likely than controls tomisinterpret averted gaze as directed at them, despite being asaccurate at controls at correctly identifying direct gaze.Methods: In the current study we wished to explore whether thisbias was associated with activations in different brain regions inthe controls and patients. Schizophrenia patients with prominentreferential delusions and healthy controls with no history ofmental illness were shown faces while in the MRI scanner andasked to judge whether the person in the picture was lookingdirectly at them or looking away. The faces all had neutralexpressions and the only changes were in the gaze direction. Eachface was shown for 500 ms and then masked.Results: Both groups showed similar levels of accuracy in judgingdirect and averted gaze. Our contrast of interest was thedifference between false positive errors (when the averted gazewas incorrectly judged as being direct gaze) vs the true negatives(when the averted gaze was corrected judged as averted). Therewere a number of differences in brain activity in these contrastbetween the two groups. Patients showed greater activity thancontrols in the left ACC, right angular gyrus, right middletemporal gyrus, and parts of the right medial frontal lobe.Controls showed greater activity in the right temporal pole, rightmedial temporal lobe, left hippocampus, and bilateral orbito-frontal- cortex.Discussion: Differences in brain activity associated with these falsepositive errors might be related the associated self-referential biasseen in patients.

doi:10.1016/j.schres.2010.02.622

Abstracts354