PM497. Epigenetic status of LINE-1 promoters in neurons and non-neurons

s | 81 University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110–799, Republic of Korea c Institute of Human Behavioral Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110–799, Republic of Korea d Department of Psychiatry, Maeumsarang Hospital, Wanju, Jeollabuk-do, Republic of Korea *Corresponding author: Ung Gu Kang, M.D., Ph. D. Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110–744, Republic of Korea. Tel: 82-2-2072-2296; Fax: 82-2-744-7241; E-mail: [email protected] Abstract Traditionally, delusions have been considered to be the products of misinterpretation and irrationality. However, some theorists have argued that delusions are normal or rational cognitive responses to abnormal experiences. That is, when a recently experienced peculiar event is more plausibly explained by an extraordinary hypothesis, confidence in the veracity of this extraordinary explanation is reinforced. As the number of such experiences, driven by the primary disease process in the perceptual domain, increases, this confidence builds and solidifies, forming a delusion. We tried to understand the formation of delusions using a computer simulation based on Bayesian inference. We found that (1) Even if a delusional explanation is only marginally more plausible than a non-delusional one, the repetition of the same experience results in a firm belief in the delusion. (2) The same process explains the systematization of delusions. (3) If the perceived plausibility of the explanation is not consistent but varies over time, the development of a delusion is delayed. Additionally, this model may explain why delusions are not corrected by persuasion or rational explanation and why the antipsychotics have limited anti-delusional effect. This Bayesian inference perspective can be a mathematical model of delusions and also considered a way to understand delusions in terms of rational human heuristics. However, such experiences of “rationality” can lead to irrational conclusions, depending on the characteristics of the subject.Traditionally, delusions have been considered to be the products of misinterpretation and irrationality. However, some theorists have argued that delusions are normal or rational cognitive responses to abnormal experiences. That is, when a recently experienced peculiar event is more plausibly explained by an extraordinary hypothesis, confidence in the veracity of this extraordinary explanation is reinforced. As the number of such experiences, driven by the primary disease process in the perceptual domain, increases, this confidence builds and solidifies, forming a delusion. We tried to understand the formation of delusions using a computer simulation based on Bayesian inference. We found that (1) Even if a delusional explanation is only marginally more plausible than a non-delusional one, the repetition of the same experience results in a firm belief in the delusion. (2) The same process explains the systematization of delusions. (3) If the perceived plausibility of the explanation is not consistent but varies over time, the development of a delusion is delayed. Additionally, this model may explain why delusions are not corrected by persuasion or rational explanation and why the antipsychotics have limited anti-delusional effect. This Bayesian inference perspective can be a mathematical model of delusions and also considered a way to understand delusions in terms of rational human heuristics. However, such experiences of “rationality” can lead to irrational conclusions, depending on the characteristics of the subject. PM497 Epigenetic status of LINE-1 promoters in neurons and non-neurons Risa Watanabe1, Miki Bundo2, Eri Hashimoto3, Takao Ishii3, Kazuya Iwamoto2, Kiyoto Kasai2, Tadafumi Kato4, Yui Murata2, Masaki Nishioka2, Yutaka Sawai2, Siro Simizu1, Junko Ueda4, Wataru Ukai3 1Keio University, Japan, 2The University of Tokyo, Japan, 3Sapporo Medical University, Japan, 4RIKEN BSI, Japan Abstract Human retrotransposon LINE-1 (L1) plays important roles in transcriptional regulation and genome stability. We previously discovered an increase of L1 copy number in the brain tissues of patients with schizophrenia (Bundo et al., Neuron, 2014). To understand the L1 activities in human brains, we investigated distribution of 5-methyl cytosine (5mC) and 5-hydroxymethyl cytosine (5hmC) in the L1 promoter regions of human neurons and non-neurons. We separated prefrontal cortex cells into neuronal and non-neuronal nuclei by NeuN-based nuclei sorting, and performed comprehensive analysis on mC and hmC. We found that full length L1 promoters in neuronal nuclei manifest characteristic mC and hmC pattern in accordance with L1 evolution. Younger L1 subfamilies had less mCs and more possibilities of containing hmCs in their promoters. This pattern was unique to L1 promoters of neuronal nuclei, and independent of the genomic context of L1 insertion. On the other hand, such pattern was not observed in non-neurons or non-full length L1s. Our findings suggest that L1 has distinctive roles in transcriptional regulation in neurons.Human retrotransposon LINE-1 (L1) plays important roles in transcriptional regulation and genome stability. We previously discovered an increase of L1 copy number in the brain tissues of patients with schizophrenia (Bundo et al., Neuron, 2014). To understand the L1 activities in human brains, we investigated distribution of 5-methyl cytosine (5mC) and 5-hydroxymethyl cytosine (5hmC) in the L1 promoter regions of human neurons and non-neurons. We separated prefrontal cortex cells into neuronal and non-neuronal nuclei by NeuN-based nuclei sorting, and performed comprehensive analysis on mC and hmC. We found that full length L1 promoters in neuronal nuclei manifest characteristic mC and hmC pattern in accordance with L1 evolution. Younger L1 subfamilies had less mCs and more possibilities of containing hmCs in their promoters. This pattern was unique to L1 promoters of neuronal nuclei, and independent of the genomic context of L1 insertion. On the other hand, such pattern was not observed in non-neurons or non-full length L1s. Our findings suggest that L1 has distinctive roles in transcriptional regulation in neurons. PM498 Investigation of feelings toward taking blonanserin and risperidone in schizophrenia patients: part 2 Yoshihisa Shoji, Hiroko Yanagimoto, Masayuki Inoue, Youhei Ishii, Yusuke Kato, Kiichiro Morita, Naohisa Uchimura, Yuji Yamashita Cognitive and Molecular Research Institute of Brain Diseases, Kurume