S15. HERITABILITY AND CORRELATION TO SCHIZOPHRENIA SPECTRUM DISORDERS OF CEREBRAL BLOOD FLOW MEASURED BY PSEUDO-CONTINUOUS ARTERIAL SPIN LABELING IN DANISH TWINS

Regional cerebral blood flow (rCBF) has been found altered in the thalamus, frontal regions and the putamen of patients with schizophrenia. It is not known if these changes in rCBF are due to genetic influences, but findings of altered rCBF in first degree relatives of patients with schizophrenia (1) indicate a familial and possibly genetic influence. A study design including discordant monozygotic (MZ) and dizygotic (DZ) twins provides the possibility to estimate heritability and correlation to disease, and to infer if a correlation is influenced by genetic or environmental factors. Our hypothesis was that rCBF in the thalamus, the frontal lobes and the putamen would be heritable and altered in schizophrenia spectrum disorder (F2x.x), and that this correlation would be influenced by genetic factors. Additional similar analyses were performed limiting the sample to include only proband pairs with narrow schizophrenia (F20.x) and healthy controls. We included 22 complete MZ and 20 complete DZ twin pairs concordant or discordant for schizophrenia spectrum disorder (ICD 10 F2x.x) and 27 complete MZ and 18 complete DZ healthy control pairs by linking The Danish Twin Register and The Danish Psychiatric Central Research Register. Twenty-five additional twins were analyzed without their siblings. rCBF was measured in the thalamus, the frontal lobes and the putamen with pseudo-continuous arterial spin-labeling on a 3 tesla magnetic resonance scanner, and structural equation modelling was used for twin statistics. We found rCBF in the frontal lobes to be heritable (h2=0.44, [0.22 – 0.60]), but there was no significant correlation to disease. In the left thalamus rCBF correlated to schizophrenia spectrum disorders (r=0.17, 95% CI [0.03 - 0.31]; p = 0.02), the same correlation was found in both the left (r=0.19, [0.05–0.32]; p=0.007) and the right putamen (r=0.18, [0.03–0.32]; p=0.02). When the sample was limited to schizophrenia (F20.x) patients only, we found significant shared genetic influences between rCBF in the left putamen and liability for schizophrenia (phenotypic correlation=0.44 [0.28–0.58], p<0.001). In this the only study of its kind we find CBF in the frontal lobes to be heritable, and CBF in the thalamus and the putamen to be altered in schizophrenia spectrum disorders. Moreover, increased putaminal perfusion in patients with schizophrenia was influenced by genetic factors. This suggests that higher CBF in the left putamen could possibly serve as a marker of genetic vulnerability for schizophrenia. Reference: 1. Blackwood DH, Glabus MF, Dunan J, O’Carroll RE, Muir WJ EK. Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia. Correlations with memory and P300. Br J psychiatry. 1999;175:357–366.