PM338. Investigation of the association of rare single nucleotide variants in methyl-CpG-binding domain protein 5 (MBD5) with phenotypes of autism spectrum disorders and schizophrenia.

s | 23 reduction of inflammatory markers. Next PG decreases microglia activation after FCI. Our finding suggests that neuroactive steroids have a relevant role in the prevention of ischemic outcome in immature brain. This study was supported by grants GACR P304/12/G069, P304/14/20613S, P303/12/1464, GAUK project No.165115, TACR-TE01020028 and institutional support RVO: 67985823 and CZ.2.16/3.1.00/22197; NPU I(LO) MSMT-3487/2013 (National Program of Sustainability). PM336 Early Antipsychotic Treatment in Childhood/ Adolescent Period has Long-term Effects on Dopamine Receptors of Adult Rat Brains Michael De Santis 1,2, Xu-Feng Huang 2, Chao Deng 1,2 1 Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, 2522, NSW, Australia 2 School of Medicine, University of Wollongong, Wollongong, 2522, NSW, Australia Abstract Background: Prescription/use of antipsychotic drugs (APDs) in children is increasing rapidly worldwide, despite serious limitations in the safety and efficacy of APD use on the developing brain. Whilst APDs are known to have a high affinity for dopamine (DA) receptors to produce therapeutic effects, DA receptors are also involved in critical neurodevelopmental processes. This study investigated the long-term effects of childhood/adolescent APD use on DA receptors in adult brains. Methods: Male and female rats (n=6/group) were treated with Aripiprazole (1 mg/kg), Olanzapine (1 mg/kg) and Risperidone (0.3 mg/kg), 3 times/day from postnatal day (PD) 22–50. Animals were sacrificed on PD106. Levels of DA D1R and D2R were investigated via quantitative autoradiographic and western blot techniques. Results: In comparison to controls, D1R protein levels were significantly decreased following Risperidone treatment in the nucleus accumbens (NAc) of male rats (p<0.01), and Aripiprazole treatment in the ventral tegmental area of females (p<0.001). Furthermore, D2R levels were increased in the prefrontal cortex of female rats (p<0.05), with a trend to decrease in the Hippocampus of males (p=0.099). Trends to significant increases of D1R and D2R bindings were found in female rats. In comparison to controls, Risperidone increased D1R binding in the Hippocampus (p=0.077), whilst Olanzapine increased D2R binding in the NAc (p=0.054). Conclusions: Long-term changes to D1R and D2R were uncovered following childhood/adolescent APD treatment, indicating the potential long-term effects of APD use on the DA neurotransmitter system during the critical neurodevelopmental window. Furthermore, differing effects of childhood APD treatment on D1R and D2R were found across both genders and APD treatment groups. Further investigations into the neural mechanisms involved for observed differences across drug treatment groups may shed further light on potential chronic effects of APD in the young population. (M. De Santis was supported by an AustralianBackground: Prescription/use of antipsychotic drugs (APDs) in children is increasing rapidly worldwide, despite serious limitations in the safety and efficacy of APD use on the developing brain. Whilst APDs are known to have a high affinity for dopamine (DA) receptors to produce therapeutic effects, DA receptors are also involved in critical neurodevelopmental processes. This study investigated the long-term effects of childhood/adolescent APD use on DA receptors in adult brains. Methods: Male and female rats (n=6/group) were treated with Aripiprazole (1 mg/kg), Olanzapine (1 mg/kg) and Risperidone (0.3 mg/kg), 3 times/day from postnatal day (PD) 22–50. Animals were sacrificed on PD106. Levels of DA D1R and D2R were investigated via quantitative autoradiographic and western blot techniques. Results: In comparison to controls, D1R protein levels were significantly decreased following Risperidone treatment in the nucleus accumbens (NAc) of male rats (p<0.01), and Aripiprazole treatment in the ventral tegmental area of females (p<0.001). Furthermore, D2R levels were increased in the prefrontal cortex of female rats (p<0.05), with a trend to decrease in the Hippocampus of males (p=0.099). Trends to significant increases of D1R and D2R bindings were found in female rats. In comparison to controls, Risperidone increased D1R binding in the Hippocampus (p=0.077), whilst Olanzapine increased D2R binding in the NAc (p=0.054). Conclusions: Long-term changes to D1R and D2R were uncovered following childhood/adolescent APD treatment, indicating the potential long-term effects of APD use on the DA neurotransmitter system during the critical neurodevelopmental window. Furthermore, differing effects of childhood APD treatment on D1R and D2R were found across both genders and APD treatment groups. Further investigations into the neural mechanisms involved for observed differences across drug treatment groups may shed further light on potential chronic effects of APD in the young population. (M. De Santis was supported by an Australian Rotary Health scholarship). PM337 Treatment of catatonia in autism spectrum disorder: 2 case reports and literature review K. Yamamoto 1, D. Sasayama 1, S. Yui 2, T. Hagiwara 1, S. Inuzuka 3, Y. Harada 3,H. Honda 1, S. Washizuka 1 1 Shinshu University Hospital, Matsumoto, Japan 2 Nagano Red Cross Hospital 3 Nagano Prefectural Mental Wellness Center-Komagane Abstract Objectives: Catatonia is a severe complication of autism spectrum disorders characterized by increased slowness, difficulty in initiating actions, and increased passivity. The aim of this study is to describe 2 patients diagnosed with autism spectrum disorder who presented with catatonia and to provide a review of literature. Results: Increasing recognition is being given to catatonic symptoms presenting in children and adolescents with autism spectrum disorder. Recent studies report that high doses of benzodiazepines and the use of electroconvulsive treatment are effective in these conditions. Case reports: Two cases of high functioning girls diagnosed with autism spectrum disorder are presented. The first case was a 15 year-old girl who presented with freezing in peculiar postures with difficulty initiating movement, slow verbal responses, abnormal repetitive movements, and difficulty crossing demarcation lines. Complete remission of catatonic symptoms was achieved by improvement of family functioning and provision of safe and organized environment along with 6 mg per day of lorazepam. The second case was an 11 year-old girl who also presented with difficulty initiating movement and crossing lines. She achieved partial remission by environmental management and use of ethyl loflazepate, a long-acting benzodiazepine. Conclusions: The present case reports showed that psychological stress may be a precipitating factor for exacerbation of catatonia in patients with autism spectrum disorder and that catatonia in patients with autism spectrum disorder is not restricted to those with low intelligence. High dose benzodiazepine such as lorazepam and ethyl loflazepate may be effective and well tolerated in treating catatonic symptoms of autism spectrum disorder.Objectives: Catatonia is a severe complication of autism spectrum disorders characterized by increased slowness, difficulty in initiating actions, and increased passivity. The aim of this study is to describe 2 patients diagnosed with autism spectrum disorder who presented with catatonia and to provide a review of literature. Results: Increasing recognition is being given to catatonic symptoms presenting in children and adolescents with autism spectrum disorder. Recent studies report that high doses of benzodiazepines and the use of electroconvulsive treatment are effective in these conditions. Case reports: Two cases of high functioning girls diagnosed with autism spectrum disorder are presented. The first case was a 15 year-old girl who presented with freezing in peculiar postures with difficulty initiating movement, slow verbal responses, abnormal repetitive movements, and difficulty crossing demarcation lines. Complete remission of catatonic symptoms was achieved by improvement of family functioning and provision of safe and organized environment along with 6 mg per day of lorazepam. The second case was an 11 year-old girl who also presented with difficulty initiating movement and crossing lines. She achieved partial remission by environmental management and use of ethyl loflazepate, a long-acting benzodiazepine. Conclusions: The present case reports showed that psychological stress may be a precipitating factor for exacerbation of catatonia in patients with autism spectrum disorder and that catatonia in patients with autism spectrum disorder is not restricted to those with low intelligence. High dose benzodiazepine such as lorazepam and ethyl loflazepate may be effective and well tolerated in treating catatonic symptoms of autism spectrum disorder. PM338 Investigation of the association of rare single nucleotide variants in methyl-CpG-binding domain protein 5 (MBD5) with phenotypes of autism spectrum disorders and schizophrenia. Kanako Ishizuka, Branko Aleksic, Wang Chenyao, Hiroki Kimura, Itaru Kushima, Takashi Okada, Norio Ozaki, Yota Uno Nagoya University Graduate School of Medicine, Japan Abstract The MBD5 gene has been widely cited as a risk gene for neurodevelopmental features. Both partial and complete deletions of MBD5 involving coding and/or non-translated exons are resulted in autism spectrum disorders (ASD), intellectual disability and epilepsy. A significant excess of a rare single nucleotide variant (SNV) in MBD5 coding exon have been detected in ASD patients. The phenotypes observed in patients having disruption of MBD5 include autistic-like symptoms, developmental delay, behavioral problems, repetitive behaviors and seizures. The aim of the present study was to investigate the association between rare MBD5 variants and neuropsychiatric pathogenesis. A total of 192 ASD (mean age ± SD = 16.3 ± 8.4 years; 77.6% male) and 370 schizophrenia (mean age ± SD, 49.7 ± 14.8 years; 53.0% male) individuals participated. First, we conducted exon-targeted resequencing of MBD5 with next-generation sequencing technology in 562 Japanese patients and detected 12 rare missense variants. We compared phenotypes of patients having these variants with the core characteristicsThe MBD5 gene has been widely cited as a risk gene for neurodevelopmental features. Both partial and complete deletions of MBD5 involving coding and/or non-translated exons are resulted in autism spectrum disorders (ASD), intellectual disability and epilepsy. A significant excess of a rare single nucleotide variant (SNV) in MBD5 coding exon have been detected in ASD patients. The phenotypes observed in patients having disruption of MBD5 include autistic-like symptoms, developmental delay, behavioral problems, repetitive behaviors and seizures. The aim of the present study was to investigate the association between rare MBD5 variants and neuropsychiatric pathogenesis. A total of 192 ASD (mean age ± SD = 16.3 ± 8.4 years; 77.6% male) and 370 schizophrenia (mean age ± SD, 49.7 ± 14.8 years; 53.0% male) individuals participated. First, we conducted exon-targeted resequencing of MBD5 with next-generation sequencing technology in 562 Japanese patients and detected 12 rare missense variants. We compared phenotypes of patients having these variants with the core characteristics 24 | International Journal of Neuropsychopharmacology, 2016 associated with MBD5 SNVs, but no typical characteristics have been observed. Although rare SNVs in MBD5 identified in our study may not have marked impact on the neurodevelopmental features, the exact molecular mechanisms and networks affected by MBD5 variants in SCZ and ASD remain unclear. Useful model systems that can address these questions will be needed to assess the impact of the SNVs discovered here. This study is important to understand the burden of rare SNVs in MBD5. All procedures performed in this study involving human participants were approved by the Ethics Committee of the Nagoya University Graduate School of Medicine and conducted in accordance with the Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from the participants and from the parents of the patients under 20 years old. PM339A The GRIN2B and GRIN2A genes are associated with continuous performance test variables in attentiondeficit/hyperactivity disorder Soo Yeon Kim, Sumin Lee Seoul National University Hospital, Republic of Korea Running head: NMDA receptor genes and CPT in ADHD Abstract Background: Previous genetic studies have reported an association between attention-deficit/hyperactivity disorder (ADHD) and N-methyl-D-aspartate (NMDA) receptor genes. However, the neuropsychological impacts of NMDA genes in ADHD have not been identified. We examined the association between two NMDA receptor subunit-encoding genes (GRIN2A and GRIN2B) and continuous performance test (CPT) variables in ADHD and healthy controls. Methods: A total of 253 ADHD patients and 98 healthy controls aged 6–17 years were recruited, and a Korean version of the CPT was administered to all participants. Each polymorphism was dichotomized into two groups, and the diagnosis, gene, and diagnosis-gene interaction effects on the CPT variables were examined after adjusting for age, sex and IQ. Results: Significant differences were detected between the ADHD and control group with regard to all CPT variables (p values < 0.05). There were significant genotype effects onBackground: Previous genetic studies have reported an association between attention-deficit/hyperactivity disorder (ADHD) and N-methyl-D-aspartate (NMDA) receptor genes. However, the neuropsychological impacts of NMDA genes in ADHD have not been identified. We examined the association between two NMDA receptor subunit-encoding genes (GRIN2A and GRIN2B) and continuous performance test (CPT) variables in ADHD and healthy controls. Methods: A total of 253 ADHD patients and 98 healthy controls aged 6–17 years were recruited, and a Korean version of the CPT was administered to all participants. Each polymorphism was dichotomized into two groups, and the diagnosis, gene, and diagnosis-gene interaction effects on the CPT variables were examined after adjusting for age, sex and IQ. Results: Significant differences were detected between the ADHD and control group with regard to all CPT variables (p values < 0.05). There were significant genotype effects on omission errors (p = 0.039) and response time standard deviations (p = 0.001) by GRIN2B variants and on omission errors (p = 0.00) and response time standard deviations (p=0.049) by GRIN2A variants. The GRIN2B C/C genotype group had committed more omission errors (p = 0.005) and had higher response time standard deviation (p < 0.001) scores than the C/T + T/T group in ADHD, but this association was not found in controls. The C/C genotype showed a longer response time only in the control group (p = 0.002). Omission errors differed according to GRIN2A genotype (with more impairment with the G/G genotype) in ADHD patients (p < 0.001), but not in controls. Conclusion: These results suggest that the genetic variants of the GRIN2B and GRIN2A genes confer an increased susceptibility to attentional impairment in ADHD patients. PM339B Association between violence aggression and corticotropin-releasing hormone receptor 1 gene polymorphism in male adolescents LIU li, YU shunying, SHAO yang, ZHANG ran,XIE bin. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine,Shanghai 200030, China. Tel:021-34289888. Abstract Objective: To study the association between Corticotropinreleasing hormone receptor 1(CRHR1) gene polymorphism with violence aggression in male adolescents. Methods: Two tagSNPs polymorphisms(CRHR1,rs242924, rs17689966) were genotyped by TaqMan SNP genotyping assay for 138 violence young male offenders,98 non-violence young male offenders and 153 normal adult controls. The distribution of allelic and genotypic frequencies in the case and control groups was analyzed. The violence young male offenders are divided into two sub-groups according to whether accompanied with Conduct Disorder symptoms. The two sub-groups are then respectively compared with the normal control group about the distribution of allelic and genotypic frequencies. Results: The frequency of G allele in rs242924 of CRHR1 gene in violence group was higher than that of the normal control group (10.5% vs. 4.9%, P<0.017, OR=2.29, 95%CI=1.13~4.62). There were significant differences in genotype frequency of rs242924 among the three groups (χ2=9.916, P=0.024). Further analysis found that there is significant difference in genotype frequency in violence group compared with normal control group(P=0.032). There were no significant differences between the other groups. After the violence young male offenders divided into two sub-groups, there were no significant differences in allelic and genotypic frequencies among the three groups. Conclusions: The variance of CRHR1 gene polymorphism may play a role in violent aggression in male adolescents, and should be further researched.Objective: To study the association between Corticotropinreleasing hormone receptor 1(CRHR1) gene polymorphism with violence aggression in male adolescents. Methods: Two tagSNPs polymorphisms(CRHR1,rs242924, rs17689966) were genotyped by TaqMan SNP genotyping assay for 138 violence young male offenders,98 non-violence young male offenders and 153 normal adult controls. The distribution of allelic and genotypic frequencies in the case and control groups was analyzed. The violence young male offenders are divided into two sub-groups according to whether accompanied with Conduct Disorder symptoms. The two sub-groups are then respectively compared with the normal control group about the distribution of allelic and genotypic frequencies. Results: The frequency of G allele in rs242924 of CRHR1 gene in violence group was higher than that of the normal control group (10.5% vs. 4.9%, P<0.017, OR=2.29, 95%CI=1.13~4.62). There were significant differences in genotype frequency of rs242924 among the three groups (χ2=9.916, P=0.024). Further analysis found that there is significant difference in genotype frequency in violence group compared with normal control group(P=0.032). There were no significant differences between the other groups. After the violence young male offenders divided into two sub-groups, there were no significant differences in allelic and genotypic frequencies among the three groups. Conclusions: The variance of CRHR1 gene polymorphism may play a role in violent aggression in male adolescents, and should be further researched. PM340 A resting-state functional magnetic resonance imaging investigation of the effectiveness of an anti-bullying intervention for adolescent perpetrators Bung-Nyun Kim1, Johanna Inhyang Kim1, Yun-hyong Kang2, Kuk-ju Kweon3 1Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea. 2 Suicide and School Mental Health Institute, Hallym University, Anyang, Republic of Korea 3Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Abstract Objective: The purpose of this study was to investigate the effectiveness of an anti-bullying intervention targeted towards school bullying perpetrators using assessments of brain activity, cognitive function, and behavior. Method: A total of 25 adolescent bullying perpetrators participated in an anti-bullying program. Prior to and after participation, resting-state functional magnetic resonance imaging (rs-fMRI) scans, the Wisconsin Card Sorting Test (WCST), and the Child Behavior Checklist (CBCL) was completed. Changes in the fractional amplitude of low-frequency fluctuations (fALFF) and scores on the WCST and CBCL were evaluated in the entire group and also separately in 2 groups that were categorized by commission of a single assault or repetitive assaults. The associations between changes in fALFF with the CBCL scores were examined. Results: Following the intervention, all participants exhibited significant decreases in the subscores of the CBCL andObjective: The purpose of this study was to investigate the effectiveness of an anti-bullying intervention targeted towards school bullying perpetrators using assessments of brain activity, cognitive function, and behavior. Method: A total of 25 adolescent bullying perpetrators participated in an anti-bullying program. Prior to and after participation, resting-state functional magnetic resonance imaging (rs-fMRI) scans, the Wisconsin Card Sorting Test (WCST), and the Child Behavior Checklist (CBCL) was completed. Changes in the fractional amplitude of low-frequency fluctuations (fALFF) and scores on the WCST and CBCL were evaluated in the entire group and also separately in 2 groups that were categorized by commission of a single assault or repetitive assaults. The associations between changes in fALFF with the CBCL scores were examined. Results: Following the intervention, all participants exhibited significant decreases in the subscores of the CBCL and