Association Study of Tyrosine Hydroxylase and Tryptophan Hydroxylase with Schizophrenia / 신경정신의학

Neurochemical investigation has played a major role in the search for the cause of schizophrenia. Among many hypotheses, dopamine hypothesis of schizophrenia prevails despite much criticism and qualification. Recently, evidences showing the atypical antipsychotics act via serotonergic mechanism suggest serotonin system as an etiologic factor for schizophrenia. We examined the possibility of the association of enzymes critical for the synthesis of serotonin (tryptophan hydroxylase, TPH) and dopamine (tyrosine hydroxylase, TH) with schizophrenia. The regions of DNA that has been known to be polymorphic were amplified using polymerase chain reaction from the peripheral blood cells of 374 biologically unrelated schizophrenic patients and 393 healthy controls. RFLP (A218C) and VNTR polymorphism (intron 1) were examined for TPH and TH, respectively. The patterns of polymorphisms and the frequencies of each allele were not significantly different between the control and the patient groups, suggesting no possible associations of the genetic polymorphisms of TPH and TH genes and schizophrenia. However, in schizophrenics, the frequency of A type allele was significantly higher in positive group than negative group. Thess findings suggest the association of positive schizophrenia with A type allele of TH gene.

The Effects of Psychotropic Drugs on the beta-Amyloid-Induced Cytotoxicity in PC12 Cells / 신경정신의학

OBJECTIVE: Amyloid beta protein(Abeta) has been regarded to be toxic to neurons in vitro. However, the mechanism of action leading to neuronal death remains unknown. In this study, we report the effects of psychotropic drugs, that are often prescribed for the improvement of psychotic and depressive symptoms in dementia of the Alzheimer's type, on the beta-amyloid-induced cytotoxicity in rat pheochromocytoma(PC12) cells. METHODS: We treated antipsychotics(chlorpromazine, haloperidol, and risperidone) and antidepressants(amitriptyline, fluoxetine, and moclobemide) at 0.1-10 microM concentrations before application of Abeta(10 microM), and compared with control in the absence of psychotropic drugs in cultured PC12 cells. RESULTS: 1) Chlorpromazine, haloperidol and risperidone significantly reduced Abeta-induced cytotoxicity in PC12 cells. 2) Amitriptyline, fluoxetine, and moclobemide significantly reduced Abeta-induced cytotoxicity in PC12 cells. CONCLUSION: Our results suggest that psychotropic drugs in the treatment of dementia of Alzheimer's type may protect the neural cells as well as control neurotransmitter activities.

VNTR Polymorphism of Tyrosine Hydroxylase Gene Intron 1 in Schizophrenics

Until recently, the etiology of schizophrenia was generally attributed to abnormalities in dopaminergic neurotransmission. Specifically, an excess of dopaminergic activity in the mesolimbic system has been postulated to produce the positive symptoms, while decreased dopaminergic activity in the mesocortical system has been suggested to cause negative symptoms. Accordingly, we performed an association study of schizophrenia with TH gene. Three hundred and seventy four biologically unrelated schizophrenic patients meeting DSM-III-R criteria from Kangnam St. Mary's Hospital affiliated with Catholic university of Korea were recruited for our study. The 393 healthy controls were volunteers for DNA library of Kangnam St. Mary's Hospital without personal or family history of psychiatric and neurologic illness. DNA was extracted from peripheral mononuclear cells and polymorphic region was amplified by polymerase chain reaction. TH intron 1 VNTR polymorphism was typed by silver staining. The allele distributions of TH gene were not different between schizophrenics and controls. However, the frequency of allele A was significantly higher in positive group than that of negative group of schizophrenics. These findings suggest that poitive schizophrenia may be associated with allele A of TH gene.

Increased Synthesis of IL1beta in Monocytes by Examination Stress / 신경정신의학

OBJECTIVES: There is now some evidence that, in humans, psychological stress may affect immune and neuroendocrine system. In stress response, cytokines are known to orchestrate the cellular interaction of immune system and act as a major messenger in a communication with CNS. Specifically, IL1beta has been reported to be colsely related with stress induced behavior change, such as depression. Accordingly, we assessed cytokine production by peripheral blood mononuclear cells (PBMC) before and after an academic examination in 45 healthy medical students. Furthermore the possibility that IL1beta TaqI polymorphism may be associated with stress response of IL1beta production was investigated. METHODS: Blood samples were collected on the day of examination and at the second week after examination. For cytokine assay seperated PBMC were incubated for 3 days at 37 degrees C, 5% CO2. DNA was prepared by Ficoll-paque method and polymorphic region was amplified by PCR. After TaqI restriction, products were seperated by 15% polyacrylamide gel electrophoresis. RESULTS: IL1beta production and stress score were significantly higher on the examination day. The change of stress score was significantly correlated with the change of IL1beta production. However, the frequency of allele A2 was too low that the significance of genetic association could not be properly estimated. CONCLUSION: This study reports that psychological stress is accompanied by an increased production of IL1 beta with significant correlation.

Association of Alcohol Dependence with the Dopamine Transporter Gene Polymorphism / 신경정신의학

OBJECTIVES: Alcoholism is known to be a heritable disease. It has been hypothesized that dopamineergic systems play an important heritable role in human behavor related to alcohol dependence, such as alcohol seeking. Therefore, genes involved in this pathway, including dopamine transporter(DAT1) which is responsible for taking released dopamine back up into presynaptic terminals and terminating dopaminergic activity, are potential candidate that may affect susceptibility to alcoholism. Analysis of a 40-base pair(bp)repeat(VNTR)in the 3'untranslated region of the DAT1 gene revealed variable number of the repeat ranging from 3 to 11 copies. Therefore, in the present study, we examined the association between alcoholism and VNTR polymorphism of DAT1. METHODS: Genomic DNA analysis with polymerase chain reaction(PCR)was used to identify the presence of a VNTR polymorphism. It was carried out within a group of 94 alcoholic patients and 113 normal controls. RESULTS: 1)There were no significant differences in allelic or genotype frequencies between the group of alcoholic patients and controls. 2)There were no significant differences in the first drinking age, onset age and latency of alcoholism according to DAT1 genotypes. 3)There was a significant difference in allelic frequencies between alcoholics with family history and those without family history. CONCLUSIONS: These results suggested that VNTR polymorphism of DAT1 is unlikely to be a factor in the genetic etiology of alcoholism, but might be related to familial transmission of alcoholism.

An Association Study of Schizophrenics and Their Clinical Variables with Tryptophan Hydroxylase Gene Polymorphism / 신경정신의학

OBJECTIVES: The genetic polymorphism of tryptophan hydroxylase (TPH) the rate-limiting enzyme in the biosynthesis of serotonin, has been to be related with various psychiatric disorders such as bipolar disorders. However, the role of TPH gene polymorphism in schizophrenia is totally unknown. Author examined the association of the TPH gene polymorphism with the development and the clinical variables of schizophrnia. METHODS: Genomic DNAs from 217 schizophrenic patients and 236 healthy controls were isolated, and TPH gene was amplified using PCR. Amplified TPH DNA was digested with NheI and the polymorphism was examined by electrophoresis on agarose gel. RESULTS: The allele frequencies and the genotypes of TPH gene were not significantly different between the schizophrenics and the control groups. They were also not associated with most of the clinical variables of schizophrenia such as subtypes, suicidal ideation, age at onset, and family histories. Among the clinical variables, only suicidal rate was highly correlated with genotype 218C/C. CONCLUSION: We found possible association of the suicical behavior with 218C/C polymorphism. However, it seems that A218C polymorphism of TPH gene does not associated with the development and other clinical variables of schizophrenia.

An Association Stufy of the 5HT2A/T102C Polymorphism with Schizophrenia and Clinical Subtype / 신경정신의학

OBJECTIVES: Family, twin and adoption studies indicate that genetic factors play a crucial role in the etiology of schizophrenia. However, mode of inheritance of schizophrenia is uncertain, and genes for schizophrenia have not yet been identified despite extensive studies due to the complexity of the genetics of schizophrenia. Currently, 5HT2A receptor gene has attracted considerable interest as a susceptibility gene of schizoph,enia since the 5HT2A receptor has been known as one of the major target sites of atypical neuroleptics. We conducted an association study of T102C polymorphism in the 5HT2a receptor gene in Korean schizophrenic patients using PCR-RFLF method. METHODS: Two hundered and fifty biologically unrelated schizoprenic patients meeting DSM-III-R criteria from Kangnam St. Mary's Hospital affiliated with Catholic University of Korea were recruited for our study. The patient group consisted of 123 male and 127 female subjects, aged 30.1+/-9.3years. The controls were volunteers for DNA library of Kangnam St. Mary's Hospital withoyt family history of psychiatric or neurologic illness. The control group consisted of 124 males and 112 females, aged 23.6+/-3.7year. Amplified genomic DNA was digested by MspI. The significance of genetic association of the polymorphism was estimated by the logisitc regression anlysis and ANOVA using SPSS 7.5. RESULT: The allele frequencies and the genotypic distribution 5HT2a receptor gene were not significantly different between the patient and control group. In addition the allele frequencies and the genotypes of 5HT2a receptor gene were not significantly associated with subtype of schizophrenia. However, negative symptom score according to genotype show significant differenence(F=3.828 df=2 P=0.023). CONCLUSION: It is suggested that even if the development and subtype of schizophrenia may not beassociated with T102C polymorphism of 5HT2A receptor in Korean population, T102C polymorphism may be associated with the severity of negative symptom.

VNTR Polymorphism of the Tyrosine Hydroxylase in Bipolar Patients / 신경정신의학

OBJECTIVES: Tyrosine hydroxylase(TH) is a rate-limiting enzyme in the synthesis of catecholamines, and could be a candidate gene for causing the bipolar disorders. Therefore, we designed this study to investigate the association of the VNTR(variable number of tandem repeats) polymorphic locus in the first intron of the TH gene with bipolar disorders. METHODS: We typed VNTB polymorphic region of the TH gene using PCR in 115 bipolar patients and 85 normal controls. Four types of alleles(A, B, C, D) were typed according to the difference of the repeat(TCAT)6-9 number. The frequencies of allele and genotype were compared between patients and normal controls, and in patients and normal controls allelic frequencies were compared respectively in terms of family history of affective disorders and age of onset. RESULTS: 1) The allelic frequencies were significantly lower in type A, and significantly higher in type D in patient group compared to control group. The genotype frequencies were significantly higher in type BD in patient group than in control group. 2) In comparing the allelic frequencies among patient group with and without family history and control group, there were no significant differences between groups with and without family history, whereas patient group with family history showed lower significance in type A and higher significance in type D compared to control group. 3) In comparing the allelic frequencies among patient groups with early onset and late onset and control group, patient group with early onset showed higher significance in type D than patient group with late onset and showed lower significance in type A and higher significance in type D compared to control group. CONCLUSIONS: The authors conclude that the VNTR polymorphic region of the TH gene might be associated bipolar disorders, and type A and type D alleles might be susceptibility genes of bipolar disorder.

Serum Cholesterol and Violent Behavior in Psychiatric Inpatients / 신경정신의학

OBJECTIVES: An association between serum cholesterol concentration and violent behavior has been suggested, but has not been consistently demonstrated. This study was conducted in oreder to evaluate the relation between serum cholesterol concentration and violent behavior in psychiatric inpatients who had been admitted at Uijongbu St.Mary's Hospital, the Catholic University of Korea from January 1994 to June 1995. METHODS: We divided the 127 subjects into violent(35 subjects) and non-violent group(95 subjects). According to the percentile distribution of serum total cholesterol in healthy Korean adults, the subjects were classified into four subgroups:Group 1,subjects whose cholesterol concentrations were below 26% of percentile distribution, Group 2,from 26% to 50%, group 3, 51% to 75% and group 4, above 75%. In the four cholesterol subgroups, the authors examined the incidence of violent behaviors and suicidal attempts. Within the violent group, total aggression score of four cholesterol subgroups was compared. RESULTS: 1) Among the four cholesterol subgroups, there were no significant differences in the violent behavior. 2) within the violent groups, total violent score of the four cholesterol subgroups showed no significant difference. 3) Among the four cholesterol subgroups, there were no significant differences in suicidal attempt. CONCLUSION: When the serum cholesterol concentrations of psychiatric inpatient applied to the percentile distribution of serum total cholesterol in healthy Korean adult, no association was found between serum cholesterol concentration and violent behavior and suicide attempt.

Characteristics of Violent Behavior in Psychiatric Inpatients / 신경정신의학

To evaluate the characteristics of violent behavior of psychiatric inpatients, the authors reviewed clinical records of psychiatric patients who had admitted at UiJong Bu St. Mary's Hospital from January 1994 to lune 1995. We divided the 287 subjects into violent and nonviolent group according to the presence of violent behaviors in psychiatric ward. We assessed demographic variables, clinical characteristics and violent behaviors using Overt Aggression Scale and compared these variables of violent group with nonviolent group. The results were as follows: 1) The number of violent patients was 72(25.1% of the total). 2) In terms of demographic variables, the differences between two groups in education and occupation were significant(p<.05). 3) In psychiatric diagnoses, violent group were more likely to have mania, schizophrenia and organic rental disorder in sequence but there were no differences between violent and nonviolent group. 4) The history of violent behavior was greater in violent group(p<.001) and the mode of admission was significantly different between two groups(p<.005). 5) In cluster of psychopathology on admission, more frequently found clusters of psychopathology in violent group were agitation-excitement and hostile- suspiciousness and there were significant differences between two groups(p<.001). 6) The length of stay in violent group(59.3 days)was significantly longer than nonviolent group(38.4 days)(p<.001). 7) The types of violent behavior were verbal aggression, physical aggression against objects and physical aggression against other people in frequency sequence. 8) The most frequent type of behavioral clue before violent behavior was hyperactive, loud, verbally abusive, angry, hostile(68.1%). 9) Most of violent behaviors were presented between midday and 6 pm. in resting time. 10) 62.3% of total violent behaviors were occurred within first week following admission. 11) The variables which showed significant effects on total aggression score were religion, educational status, occupation, mode of admission, psychiatric diagnosis, psychopathology on admission and history of violent behavior before admission. In summary, these results showed similar trends compared to previous studies on characteristics of psychiatric inpatients. And we fecund that more important predictors of violent behavior in practice were likely to be history of violent behavior, psychopathology on admission and behavioral cue before violent behavior.

A case of psychotic regression with cerebellar damage by sodium monfluoroacetate poisoning: after 7 years follow up / 신경정신의학

No abstract available.