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P.7.b.002 Association of DAO and DAOA genes with autism spectrum disorders in Korean boys
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P.7.c Child and adolescent disorders and treatment – Treatment (clinical)
Acknowledgments: This study was supported in part by grants: PI02/1248 (Spanish Department of Health: Healthcare Research Fund) and G03/032 (Spanish Department of Health: Healthcare Research Fund).
P.7.c Treatment (clinical) P.7.c.001 Akathisia as frequent side effect of anaesthesia with neuroleptics in patients with attention deficit/hyperactivity disorder
References [1] Bertolino A, Callicott JH, Mattay VS, et al., 2001, The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia, Biol Psychiatry, 49, 39−46. [2] Steen RG, Hamer RM, Lieberman JA, 2005, Measurement of brain metabolites by 1 H magnetic resonance spectroscopy in patients with schizophrenia: A systematic review and meta-analysis, Neuropsychopharmacology, 30, 1949−62.
P.7.b.002 Association of DAO and DAOA genes with autism spectrum disorders in Korean boys J.W.J. Jeon ° , S.H.C. Chung, J.P.H. Hong, H.I.Y. Yoo. Asan Medical Center, Psychiatric Department, Seoul, Republic of Korea Introduction: Autism spectrum disorders (ADS) are childhoodonset neurodevelopmental disorders characterized by impairments in social interaction, communication, and stereotypic behaviors. Recent evidences have suggested that glutamate neurotransmission may contribute to development of ASD. The aim of this study is to examine the association between ASD and NMDA glutamate receptor-related genes such as the D-amino acid oxidase (DAO) and the D-amino acid oxidase activator (DAOA) genes. Methods: Fifty seven Korean subjects with ASD (47 boys, 5.5±4.1 years old) were enrolled in this study. Unrelated 47 Korean family trios consisting of affected offspring with ASD, biological fathers, and mothers were also recruited. Eighty two healthy adults (69 males, 33.4±0.3 years old) were recruited for healthy comparison group. Four SNPs of the DAO gene and 2 SNPs of the DAOA gene were analyzed. Results: There were no significant transmission disequilibrium test (TDT) results in 47 complete trios, and neither in 41 male proband trios. In population-based association analyses, there were no significant differences between genotype distributions and allele frequencies in total patients, but significant differences were observed in rs3918346 (p = 0.04) and rs3825251 (p = 0.04) of the DAO gene in comparisons of boys with ASD. Conclusions: SNPs of the DAO gene were associated with ASD in Korean boys. This finding supports the possibility of functional roles for genetic variants of glutamate-related gene in the development of ASD. References [1] Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M, 1995, Autism as a strongly genetic disorder: Evidence from a British twin study, Psychol Med, 25, 1, 63−77. [2] Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, et al., 2002, Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia, Proc Natl Acad Sci USA, 99, 21, 13675−80. [3] Collier DA, Li T, 2003, The genetics of schizophrenia: Glutamate not dopamine? Eur J Pharmacol, 480, 1−3, 177−84.
J. Krause1 ° , K.H. Krause2 . 1 Outpatient Clinic, Department of Psychiatry and Psychotherapy, Ottobrunn, Germany; 2 University of Munich, Friedrich-Baur-Institute, Munich, Germany Purpose of the study: In a 13 year old boy and a 41 year old female, both suffering from attention deficit/hyperactivity disorder (ADHD), we saw extreme akathisia after general anaesthesia with premedication of neuroleptics. In the woman the symptoms worsened, when triflupromazine was given in the postoperative state. Furthermore extreme restlessness has been reported anecdotically in some children with ADHD. In former times, some anaesthesiologists used methylphenidate parenterally, when patients exhibited restlessness in the postoperative state. Meanwhile, methylphenidate is no more available as solution for parenteral application. Outgoing from these observations, in this study we looked for complications of anaesthesias in children with ADHD. Method: In a German ADHD support group for parents of children with ADHD parents were asked for their experiences with anaesthesia in their children undergoing at least one general anaesthesia, using a questionnaire. Result: 46 parents responded; from 46 children (40 boys, 6 girls, age ranging from 1 to 17 years, mean ±SD 7.41±4.00) undergoing general anaesthesia 33 were reported to have had marked restlessness, hyperactivity and aggressive behaviour after anaesthesia, in some cases worsening after additional medication with neuroleptics. Some children initially needed much more of anaesthetic agents than expected. In two children, who were known to have had received neuroleptics in a second anaesthesia carried out later, no such substances were used, and at this time anaesthesia was tolerated without any problem. Some of the patients with ADHD reported very good tolerability of ketamine and propofol, substances with a different mechanism of action compared to neuroleptics. Conclusion: Akathisia seems to be a frequent side effect of anaesthesia with neuroleptics in patients with ADHD. Meanwhile neurobiological facts are known, which may explain this pronounced reaction of patients with ADHD on anaesthesia with neuroleptic drugs: SPECT studies revealed a marked elevation of striatal dopamine transporters in most untreated patients with ADHD [1,2]. High dopamine transporter availability causes lowering of dopamine in the synaptic cleft; this can be corrected by stimulants like methylphenidate, which are specific dopamine reuptake inhibitors [3]. On the other side, down regulation of increased dopamine by blocking of dopamine receptors is thought to be the essential effect of neuroleptic drugs in patients with psychosis. As a consequence stimulants and neuroleptics seem to have antagonistic influences on dopamine. Therefore, it would be not surprising, that in patients with ADHD the symptoms are worsened, when the basically lowered dopamine will be decreased additionally by medication with neuroleptic drugs. To our knowledge, no studies exist about this aspect, which has some practical consequences for planning anaesthesia in patients with ADHD. Controlled studies concerning the effect of neuroleptics and other anaesthetic agents in patients with ADHD seem to be of interest. If our experiences will be confirmed in greater collectives, neuroleptic agents should be avoided in anaesthesia of patients with ADHD.
P.7.c Child and adolescent disorders and treatment – Treatment (clinical)
Acknowledgments: This study was supported in part by grants: PI02/1248 (Spanish Department of Health: Healthcare Research Fund) and G03/032 (Spanish Department of Health: Healthcare Research Fund).
P.7.c Treatment (clinical) P.7.c.001 Akathisia as frequent side effect of anaesthesia with neuroleptics in patients with attention deficit/hyperactivity disorder
References [1] Bertolino A, Callicott JH, Mattay VS, et al., 2001, The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia, Biol Psychiatry, 49, 39−46. [2] Steen RG, Hamer RM, Lieberman JA, 2005, Measurement of brain metabolites by 1 H magnetic resonance spectroscopy in patients with schizophrenia: A systematic review and meta-analysis, Neuropsychopharmacology, 30, 1949−62.
P.7.b.002 Association of DAO and DAOA genes with autism spectrum disorders in Korean boys J.W.J. Jeon ° , S.H.C. Chung, J.P.H. Hong, H.I.Y. Yoo. Asan Medical Center, Psychiatric Department, Seoul, Republic of Korea Introduction: Autism spectrum disorders (ADS) are childhoodonset neurodevelopmental disorders characterized by impairments in social interaction, communication, and stereotypic behaviors. Recent evidences have suggested that glutamate neurotransmission may contribute to development of ASD. The aim of this study is to examine the association between ASD and NMDA glutamate receptor-related genes such as the D-amino acid oxidase (DAO) and the D-amino acid oxidase activator (DAOA) genes. Methods: Fifty seven Korean subjects with ASD (47 boys, 5.5±4.1 years old) were enrolled in this study. Unrelated 47 Korean family trios consisting of affected offspring with ASD, biological fathers, and mothers were also recruited. Eighty two healthy adults (69 males, 33.4±0.3 years old) were recruited for healthy comparison group. Four SNPs of the DAO gene and 2 SNPs of the DAOA gene were analyzed. Results: There were no significant transmission disequilibrium test (TDT) results in 47 complete trios, and neither in 41 male proband trios. In population-based association analyses, there were no significant differences between genotype distributions and allele frequencies in total patients, but significant differences were observed in rs3918346 (p = 0.04) and rs3825251 (p = 0.04) of the DAO gene in comparisons of boys with ASD. Conclusions: SNPs of the DAO gene were associated with ASD in Korean boys. This finding supports the possibility of functional roles for genetic variants of glutamate-related gene in the development of ASD. References [1] Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M, 1995, Autism as a strongly genetic disorder: Evidence from a British twin study, Psychol Med, 25, 1, 63−77. [2] Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, et al., 2002, Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia, Proc Natl Acad Sci USA, 99, 21, 13675−80. [3] Collier DA, Li T, 2003, The genetics of schizophrenia: Glutamate not dopamine? Eur J Pharmacol, 480, 1−3, 177−84.
J. Krause1 ° , K.H. Krause2 . 1 Outpatient Clinic, Department of Psychiatry and Psychotherapy, Ottobrunn, Germany; 2 University of Munich, Friedrich-Baur-Institute, Munich, Germany Purpose of the study: In a 13 year old boy and a 41 year old female, both suffering from attention deficit/hyperactivity disorder (ADHD), we saw extreme akathisia after general anaesthesia with premedication of neuroleptics. In the woman the symptoms worsened, when triflupromazine was given in the postoperative state. Furthermore extreme restlessness has been reported anecdotically in some children with ADHD. In former times, some anaesthesiologists used methylphenidate parenterally, when patients exhibited restlessness in the postoperative state. Meanwhile, methylphenidate is no more available as solution for parenteral application. Outgoing from these observations, in this study we looked for complications of anaesthesias in children with ADHD. Method: In a German ADHD support group for parents of children with ADHD parents were asked for their experiences with anaesthesia in their children undergoing at least one general anaesthesia, using a questionnaire. Result: 46 parents responded; from 46 children (40 boys, 6 girls, age ranging from 1 to 17 years, mean ±SD 7.41±4.00) undergoing general anaesthesia 33 were reported to have had marked restlessness, hyperactivity and aggressive behaviour after anaesthesia, in some cases worsening after additional medication with neuroleptics. Some children initially needed much more of anaesthetic agents than expected. In two children, who were known to have had received neuroleptics in a second anaesthesia carried out later, no such substances were used, and at this time anaesthesia was tolerated without any problem. Some of the patients with ADHD reported very good tolerability of ketamine and propofol, substances with a different mechanism of action compared to neuroleptics. Conclusion: Akathisia seems to be a frequent side effect of anaesthesia with neuroleptics in patients with ADHD. Meanwhile neurobiological facts are known, which may explain this pronounced reaction of patients with ADHD on anaesthesia with neuroleptic drugs: SPECT studies revealed a marked elevation of striatal dopamine transporters in most untreated patients with ADHD [1,2]. High dopamine transporter availability causes lowering of dopamine in the synaptic cleft; this can be corrected by stimulants like methylphenidate, which are specific dopamine reuptake inhibitors [3]. On the other side, down regulation of increased dopamine by blocking of dopamine receptors is thought to be the essential effect of neuroleptic drugs in patients with psychosis. As a consequence stimulants and neuroleptics seem to have antagonistic influences on dopamine. Therefore, it would be not surprising, that in patients with ADHD the symptoms are worsened, when the basically lowered dopamine will be decreased additionally by medication with neuroleptic drugs. To our knowledge, no studies exist about this aspect, which has some practical consequences for planning anaesthesia in patients with ADHD. Controlled studies concerning the effect of neuroleptics and other anaesthetic agents in patients with ADHD seem to be of interest. If our experiences will be confirmed in greater collectives, neuroleptic agents should be avoided in anaesthesia of patients with ADHD.