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Association of neurotrophin-3 gene variant with severe forms of schizophrenia
174
P Poster Presentations
by Mitsuda (1942, 1954) on the basis of his clinico-genetic studies. We conducted an association study between atypical psychosis and dopamine D2 receptor gene (DRD2) using TaqI A RFLP and DRD2 Ser31 lICys31 I polymorphism. The subjects were 21 patients of atypical psychosis and 58 controls. The diagnoses of atypical psychosis were assigned according to the diagnostic criteria (TOYODA, 1988) on the basis of MITSUDA's concept, without knowing the results of DNA typing. There were no association between these DRD2 polymorphisms and atypical psychosis. These results would indicate that dopamine D2 receptor gene does not directly relate to developing atypical psychosis.
I P-15-19[
Anticipation andTriplet Repeats in Schizophrenia
A. Imamura I, Y. Okzaki I, M. Hayashida I, T. Tsujita 2, N. Niikawa 2, Y. Nakane I, S. Matsumoto 3. I Dept. of Neuropsychiatry; 2 Dept. of
Human Generics. Nagasaki University School of Medicine; 3 Michinoo Hospital, Nagasaki, Japan Anticipation is a genetic phenomenon which refers to the decrease in age at onset and the increase in disease severity in succeeding generation. Recently the expansion of triplet repeats has been shown to be correlated with anticipation in 'triplet repeats diseases', which include spinocerebellar ataxia type I. To test the hypothesis of anticipation in schizophrenia, we compared ages of onset between two generations in 22 parent-offspring pairs with DSM-III-R schizophrenia. The parentoffspring pairs included a proband which was admitted to the Nagasaki University Hospital or Michinoo Hospital between 1986-1994. We observed statistically significant decreases in age of onset in the offspring generation (Wilcoxon t =2.5, df = 21, P < 0.0001; one tailed). Although ascertainment bias could not be thoroughly ruled out in this sample, these findings suggested that the expansion of unstable DNA sequences, such as that of triplet repeats, was a possible mode of transmission in some of the patients with schizophrenia. We have compared CAG repeats lengths in 'SCAI' (the gene causing spinocerebellar ataxia type I) on chromosome 6p, between parent and offspring in 5 pairs, because recent studies have suggested a connection between DNA markers on 6p and schizophrenia. However, for a precise statement of the connection between CAG repeats lengths in 'SCAI' and schizophrenia, we have to apply this examination to more parent-offspring pairs with schizophrenia. Furthermore, another triplet repeats length in another candidate gene will be tested.
IP-15-20 I Association of Neurotrophin-3 GeneVariant with Severe Forms of Schizophrenia
S. Nanko, M. Hattori. Department of Psychiatry, Teikyo Univ. Sch. of
Med., Japan Schizophrenia is a common disease with a life time prevalence of approximately one percent. Although there is compelling evidence of an important genetic contribution to schizophrenia, the etiology remains uncertain. The recent possible neurodevelopmental etiology of schizophrenia makes neurotrophin-3 (NT-3) gene an interesting candidate locus for molecular study of schizophrenia. We searched DNA variants through the coding region and the AP-l binding site of the NT-3 gene, and found three variants. One is a missense mutation, Gly(-63)->Glu(-63) (GQG->GAG) and the others are silent mutations (a transition (A->G) at the third nucleotide of Pro( -55) and a silent change (C to T transition) at nucleotide 652). None of them have associated with schizophrenia as a whole. However, a significant difference was found in the distribution of the variant, Gly( -63)-> Glu(-63) between 61 patients and 10I controls (P = 0.004, X2 = 8.290, df = 1), when the patients were restricted to severe cases (with early-onset less than 25 years old and with duration of illness more than 10 years) based on the neurodevelopmental perspective. Individuals with homozygous or heterozygous for the allele Glu(-63) had a 2.595-fold increased risk of severe forms of schizophrenia. Although the sample size was small, these results may indicate the involvement of the variant (-63) in the pathogenesis of severe forms of this disease.
I P-15-21 I Chronic Fluvoxamine Treatment Reduces Platelet MAO Activity in Medicated Chronic Schizophrenics Henry Silver I, Natan Odnopozov 2, Nabil Jahjahl', Igor Barash
I.
Flugelman (Mazra), PsychiatricHospital, Doar Na Ashrat, Israel; 2 Rivka ZeifJHospital, Zefat, Israel I
The effect of add-on fluvoxamine on platelet MAO activity was studies in 9 chronic schizophrenic patients on steady antipsychotic treatment. Methods: Blood platelet MAO activity was assayed using radioactive technique described by Quintana (1988) with modification according to Bermeyer (1989) using 3H serotonin as substrate. The day to day CV% for mean levels of MAO activity 0.15, 1.3,3.8 mcMlh x 109 platelets was 16.0, 17.5 and 12.5, respectively. Intraseries CV% for mean levels of MAO activity of 0.15, 1.3,3.8 mcMlh x 109 platelets was 9.7,11.2 and 10.5, respectively. For quality control batching samples were pooled before analysis. results: Platelet MAO activity decreased significantly after 5 weeks of treatment and remained depressed.
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Conclusion: Since fluvoxamine does not inhibit MAO activity in vitro, the findings, which are preliminary, raise the possibility that chronic SSRI treatment may modify MAO production.
I P-15-22I Monoamine Metabolism in Acute Methamphetamine Psychosis-Comparison with Schizophrenia I, M. Fukuda 2, N. Horita 3, H. Fujimori I, H. Kazamatsuri Tokyo Metropolitan MatsuzawaHospital, Tokyo, 2 Departmentof Neuropsychiatry, Faculty of Medicine, University of Tokyo, 3 Tokyo Metropolitan Mental Health Center, Tokyo, Japan
Y. Igarashi
I.
I
The purpose of present study is to examine monoamine metabolism in acute methamphetamine psychosis (MAP) in comparison with acute schizophrenia. Subjects were 14 MAP psychotics and 26 schizophrenics. Concentrations of plasma homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenyl glycol (pMHPG) were measured on admission. I) Plasma HVA levels were significantly higher in four MAP psychotics who exacerbated after MAP use (MU; 20.00 ± 8.89 ng/ml) than in ten MAP psychotics who exacerbated without MAP use (Flashbackers FB; 8.81 ± 3.16), six schizophrenics who showed prominent anxiety and affectlabile symptoms (AF; 10.35 ± 3.23), and 20 schizophrenics without such symptoms (NAF; 11.43 ± 5.09). 2) Plasma MHPG levels were significantly elevated in AF (11.50 ± 2.95) than in NAF (6.09 ± 2.26), MU (7.00 ± 3.91) and FB (5.70 ± 1.92). 3) The ratio of pMHPG to pHVA, which could be assumed to reflect relative noradrenergic to dopaminergic activity in the central nervous system, was significantly different in the four subgroups as follows; AF (1.14 ± 0.17)>> FB (0.68 ± 0.18), NAF (0.56 ± 0.18) > MU (0.34 ± 0.07). These results suggested that FB may have monoamine metabolism similar to that in NAF.
P Poster Presentations
by Mitsuda (1942, 1954) on the basis of his clinico-genetic studies. We conducted an association study between atypical psychosis and dopamine D2 receptor gene (DRD2) using TaqI A RFLP and DRD2 Ser31 lICys31 I polymorphism. The subjects were 21 patients of atypical psychosis and 58 controls. The diagnoses of atypical psychosis were assigned according to the diagnostic criteria (TOYODA, 1988) on the basis of MITSUDA's concept, without knowing the results of DNA typing. There were no association between these DRD2 polymorphisms and atypical psychosis. These results would indicate that dopamine D2 receptor gene does not directly relate to developing atypical psychosis.
I P-15-19[
Anticipation andTriplet Repeats in Schizophrenia
A. Imamura I, Y. Okzaki I, M. Hayashida I, T. Tsujita 2, N. Niikawa 2, Y. Nakane I, S. Matsumoto 3. I Dept. of Neuropsychiatry; 2 Dept. of
Human Generics. Nagasaki University School of Medicine; 3 Michinoo Hospital, Nagasaki, Japan Anticipation is a genetic phenomenon which refers to the decrease in age at onset and the increase in disease severity in succeeding generation. Recently the expansion of triplet repeats has been shown to be correlated with anticipation in 'triplet repeats diseases', which include spinocerebellar ataxia type I. To test the hypothesis of anticipation in schizophrenia, we compared ages of onset between two generations in 22 parent-offspring pairs with DSM-III-R schizophrenia. The parentoffspring pairs included a proband which was admitted to the Nagasaki University Hospital or Michinoo Hospital between 1986-1994. We observed statistically significant decreases in age of onset in the offspring generation (Wilcoxon t =2.5, df = 21, P < 0.0001; one tailed). Although ascertainment bias could not be thoroughly ruled out in this sample, these findings suggested that the expansion of unstable DNA sequences, such as that of triplet repeats, was a possible mode of transmission in some of the patients with schizophrenia. We have compared CAG repeats lengths in 'SCAI' (the gene causing spinocerebellar ataxia type I) on chromosome 6p, between parent and offspring in 5 pairs, because recent studies have suggested a connection between DNA markers on 6p and schizophrenia. However, for a precise statement of the connection between CAG repeats lengths in 'SCAI' and schizophrenia, we have to apply this examination to more parent-offspring pairs with schizophrenia. Furthermore, another triplet repeats length in another candidate gene will be tested.
IP-15-20 I Association of Neurotrophin-3 GeneVariant with Severe Forms of Schizophrenia
S. Nanko, M. Hattori. Department of Psychiatry, Teikyo Univ. Sch. of
Med., Japan Schizophrenia is a common disease with a life time prevalence of approximately one percent. Although there is compelling evidence of an important genetic contribution to schizophrenia, the etiology remains uncertain. The recent possible neurodevelopmental etiology of schizophrenia makes neurotrophin-3 (NT-3) gene an interesting candidate locus for molecular study of schizophrenia. We searched DNA variants through the coding region and the AP-l binding site of the NT-3 gene, and found three variants. One is a missense mutation, Gly(-63)->Glu(-63) (GQG->GAG) and the others are silent mutations (a transition (A->G) at the third nucleotide of Pro( -55) and a silent change (C to T transition) at nucleotide 652). None of them have associated with schizophrenia as a whole. However, a significant difference was found in the distribution of the variant, Gly( -63)-> Glu(-63) between 61 patients and 10I controls (P = 0.004, X2 = 8.290, df = 1), when the patients were restricted to severe cases (with early-onset less than 25 years old and with duration of illness more than 10 years) based on the neurodevelopmental perspective. Individuals with homozygous or heterozygous for the allele Glu(-63) had a 2.595-fold increased risk of severe forms of schizophrenia. Although the sample size was small, these results may indicate the involvement of the variant (-63) in the pathogenesis of severe forms of this disease.
I P-15-21 I Chronic Fluvoxamine Treatment Reduces Platelet MAO Activity in Medicated Chronic Schizophrenics Henry Silver I, Natan Odnopozov 2, Nabil Jahjahl', Igor Barash
I.
Flugelman (Mazra), PsychiatricHospital, Doar Na Ashrat, Israel; 2 Rivka ZeifJHospital, Zefat, Israel I
The effect of add-on fluvoxamine on platelet MAO activity was studies in 9 chronic schizophrenic patients on steady antipsychotic treatment. Methods: Blood platelet MAO activity was assayed using radioactive technique described by Quintana (1988) with modification according to Bermeyer (1989) using 3H serotonin as substrate. The day to day CV% for mean levels of MAO activity 0.15, 1.3,3.8 mcMlh x 109 platelets was 16.0, 17.5 and 12.5, respectively. Intraseries CV% for mean levels of MAO activity of 0.15, 1.3,3.8 mcMlh x 109 platelets was 9.7,11.2 and 10.5, respectively. For quality control batching samples were pooled before analysis. results: Platelet MAO activity decreased significantly after 5 weeks of treatment and remained depressed.
-0.4.- .....
-n
__
.
Conclusion: Since fluvoxamine does not inhibit MAO activity in vitro, the findings, which are preliminary, raise the possibility that chronic SSRI treatment may modify MAO production.
I P-15-22I Monoamine Metabolism in Acute Methamphetamine Psychosis-Comparison with Schizophrenia I, M. Fukuda 2, N. Horita 3, H. Fujimori I, H. Kazamatsuri Tokyo Metropolitan MatsuzawaHospital, Tokyo, 2 Departmentof Neuropsychiatry, Faculty of Medicine, University of Tokyo, 3 Tokyo Metropolitan Mental Health Center, Tokyo, Japan
Y. Igarashi
I.
I
The purpose of present study is to examine monoamine metabolism in acute methamphetamine psychosis (MAP) in comparison with acute schizophrenia. Subjects were 14 MAP psychotics and 26 schizophrenics. Concentrations of plasma homovanillic acid (pHVA) and 3-methoxy-4hydroxyphenyl glycol (pMHPG) were measured on admission. I) Plasma HVA levels were significantly higher in four MAP psychotics who exacerbated after MAP use (MU; 20.00 ± 8.89 ng/ml) than in ten MAP psychotics who exacerbated without MAP use (Flashbackers FB; 8.81 ± 3.16), six schizophrenics who showed prominent anxiety and affectlabile symptoms (AF; 10.35 ± 3.23), and 20 schizophrenics without such symptoms (NAF; 11.43 ± 5.09). 2) Plasma MHPG levels were significantly elevated in AF (11.50 ± 2.95) than in NAF (6.09 ± 2.26), MU (7.00 ± 3.91) and FB (5.70 ± 1.92). 3) The ratio of pMHPG to pHVA, which could be assumed to reflect relative noradrenergic to dopaminergic activity in the central nervous system, was significantly different in the four subgroups as follows; AF (1.14 ± 0.17)>> FB (0.68 ± 0.18), NAF (0.56 ± 0.18) > MU (0.34 ± 0.07). These results suggested that FB may have monoamine metabolism similar to that in NAF.