Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts

OBJECTIVE: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. METHODS: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. RESULTS: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p < 0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). CONCLUSION: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

Psycho-oncological intervention in haematopoietic progenitor cell transplant (HPT): effects of emotional impact / Intervención psicooncológica en trasplante de progenitores hematopoyéticos (TPH): efectos en el impacto emocional

The aim of this work has been to determine the repercussions a psycho-oncological program has on patients who need to undergo a haematopoietic stem cell transplantation (HPT). We have studied two groups, an intervention group (n=21), formed with patients that have gone through the program of psycho-oncologic preparation previous to the transplant, and a control group (n=15), without psychological intervention. The program consists of four sessions: analysis and handling of the information, coping skills, management of stress, and preparation for the isolation. The results show that patients who receive the psychological intervention. appear to obtain minor levels in anxiety and depression and has a more adaptive perception of the passage of time and a more positive mood with more activity than the control group. However, such differences are not significant in the perception of the physical symptomatology as the amount of time in isolation increases.

El objetivo de este trabajo ha sido determinar las repercusión un programa de intervención psicooncológica sobre los pacientes candidatos a un Trasplante de Progenitores Hematopoyéticos (TPH). Participan dos grupos de pacientes, el grupo intervención (n=21), formado por los pacientes que han realizado el programa de intervención previo al trasplante, y un grupo de control (n=15), que no recibe la intervención pre-TPH. El programa consta de cuatro módulos: análisis y manejo de la información, habilidades de afrontamiento, control del estrés, y preparación familiar al aislamiento. Los resultados muestran que los pacientes que reciben la intervención psicológica obtienen niveles menores en ansiedad y depresión y tiene una percepción más adaptativa del paso del tiempo y un estado de ánimo más positivo, con más actividad que el grupo de control. Sin embargo, tales diferencias no son significativas en la percepción de la sintomatología física que aumenta con el paso del tiempo en aislamiento.

Effect of TPh on cell HepG-2 cell cycle, apoptosis and related gene expression of hepatocellular carcinoma / 中国生化药物杂志

Objective To investigate the effect of different concentrations of TPh on hepatoma cells , cell viability and and its possible mechanisms of anti-tumor.Methods The inhibitory rate of hepatoma cells and cell viability on different concentrations of TPh and time were measured by MTT assay;The morphological changes of apoptosis were observed by Hoechst 33258 straining; Cell cycle distribution was evaluated by flow cytometry (FCM).The protein expression of Bcl-2 and Bax were detected by Western blot analysis.Results MTT assay showed that TPh inhibited the proliferation of HepG-2 cells in a dose-dependent manner, and the inhibitory rate increased with the increase of concentration.The inhibitory rate was 50.9% (P<0.01).The results of Hoechst 33258 staining showed that the fluorescence intensity of hepatocellular carcinoma cells was light blue in fluorescence microscopy and bright blue fluorescence in apoptotic hepatocarcinoma cells, and the apoptosis of hepatocarcinoma cells increased with the increase of drug concentration.The percentage of cells in G0/G1 phase increased with the increase of cell cycle, and the ratio of cells in S phase was decreased in G2/M phase compared with blank control group (P<0.05);Western blot results showed that compared with the blank control group, TPh inhibited the proliferation of Bcl-2 cells in a concentration-dependent manner ( P <0.05 ) , and the number of apoptotic cells increased with the increase of drug concentration (P<0.05), and the ratio of Bcl-2/Bax in the TPh group decreased significantly (P<0.05), and the expression of Bax gene increased. Conclusion TPh inhibits cell proliferation, promotes apoptosis and induces HepG-2 to block G0/G1 phase.Its mechanism may increase the expression of Bax and decrease Bcl-2 protein expression.

Effects of baldrinal of Valeriana jatamansi on expression of CRF, TPH1 mRNA and 5-HT in rats with irritable bowel syndrome / 中国中药杂志

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P<0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P<0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.

Experimental study on abnormal expression of TPH2,DDC and MAO-A involved in depression-like behaviors of rats induced by CUS / 中国药理学通报

Aim To investigate the role of tryptophan hydroxylase-2 (TPH2),dopa-decarboxylase (DDC)and monoamine oxidase-A(MAO-A)in depression-like be-haviors induced by chronic unpredictable stress (CUS).Methods 30 male SD rats were randomly di-vided into model group(MG)and control group(CG). Rat depression model was developed by CUS for 28 consecutive days in a solitary condition.The depres-sion-like behaviors of rats were evaluated by open-field test(OFT)and forced-swimming test(FST).The real time PCR and Western blot test were used to determine the mRNA and protein expression of TPH2,DDC and MAO-A in rat telencephalon and hippocampus.Re-sults The movement scores of rats were obviously de-creased in OFT(P<0.01 ).The immobility time was obviously increased in FST (P <0.01 ).The mRNA and protein expressions of TPH2 and DDC were de-creased significantly (P <0.01,P <0.05 )and the MAO-A mRNA and protein expressions were increased significantly(P <0.01,P <0.05 )in telencephalon and hippocampus of MG rats, when compared with those in CG rats.Conclusion The TPH2,DDC and MAO-A in rat telencephalon and hippocampus were closely related with the depression-like behaviors of rats induced by CUS.

The effects of offspring's behavior and SERT and TPH during the lactation exposure to fluoxetine / 中国神经精神疾病杂志

Objective To explore the influence of the lactation exposure to fluoxetine on offspring's behavior and serotonin transporter (SERT) and tryptophan hydroxylase (TPH). Methods Six SD pregnant rats were randomly divided into 2 groups (n=3 each group). Experimental maternal rats were intraperitoneally injected with fluoxetine at a dose of 12 mg/kg from postnatal day 5 to 21. The control group were injected with the same amount of normal saline. In infancy, the offspring's weight, hair length, eye opening and auditory development were measured. The free suspension test and bur?ied food pellets test were applied to evaluate the offspring's behaviors. After postnatal day 21, all the offspring were wean. At early childhood (P35d) and adulthood (P75d), 6 offspring rats from each group were executed to examine SERT and TPH in the prefrontal cortex by immunohistochemistry. Results The offspring's weight of experimental group was significantly lower than control group (P<0.05). The sensitivity of auditory in experimental group was significantly higher than control group (P<0.01). The time of free suspension in experimental group significantly was decreased comparing to control group (P<0.01). The SERT and TPH in prefrontal cortex was significantly lower in experimental group than those in control group either at childhood (P35d) or at adulthood (P75d) (P<0.05). Conclusion Lactation exposure to fluoxetine re?sults in offspring's abnormal development and behaviors through down-regulation of SERT and TPH in the prefrontal cor?tex.

Down-regulation of monoamine neurotransmitter synthetase expression involved in CUS-induced depression of rats / 中国药理学通报

Aim To investigate whether chronically un-predictable stress (CUS)-induced depression-like be-haviors of rats is associated with the variant expression of tryptophan hydroxylase (TPH)and tyrosine hydrox-ylase (TH).Methods 30 male SD rats were ran-domly divided into depression model group(MG)and control group (CG),the former was established using CUS plus solitary condition for 28 d,whereas the latter was fed normally as five rats per cage without CUS. The open field test(OFT)and the sucrose preference test were used to evaluate depressive behaviors.Both mRNA and protein expressions of TPH and TH in hip-pocampus and forebrain cortex were determined by re-al-time fluorescent quantitative PCR and western blot (WB),respectively.Results MG rats showed obvi-ous depressive behaviors with much lower locomotive activity and sucrose preference than CG.Meanwhile, the mRNA and protein expressions of TPH and TH also significantly decreased in MG rats,compared with CG rats.Conclusion The depression behaviors of rats in-duced by CUS may be associated with down-regulation of TPH and TH expression.

Infección por Mycobacterium tuberculosis en una niña sometida a trasplante de progenitores hematopoyéticos / Mycobacterium tuberculosis infection in a pediatric patient who underwent a hematopoietic stem cell transplant

We report the case of a 10 year old girl with a relapsed acute lymphoblastic leukemia, who underwent a haploidentical hematopoietic stem cell transplant (HSCT), with grade II skin and digestive graft versus host disease, treated with corticosteroids and cyclosporine. On day + 54, she presented fever, with no other remarkable clinical findings. Imaging study showed the presence of lung and liver nodules, liver biopsy was performed. The study included histology, staining and culture for bacteria and fungi, and the preservation of a piece of tissue at -20°C for future prospective studies. Ziehl Nielsen stain was positive, and study for Mycobacterium infection was performed. Microbiological smears of tracheal and gastric aspirate, and bronchial fluid obtained by bronchoalveolar lavage (BAL) were positive. The final report confirmed Mycobacterium tuberculosis in gastric content, sputum, BAL and liver tissue, susceptible to rifampin, isoniazid, streptomycin and ethambutol, with determination of mutations for genes rpoβ and kat G (-). Tuberculosis (TB) diagnosis was confirmed. The girl received daily therapy for two months and then she continued on three times per week therapy for 9 months. Controlled by the transplant, infectious diseases and respiratory teams, the patient remained in good general condition, with radiologic resolution of pulmonary and liver involvement and negative smears. We conclude that Mycobacterium tuberculosis infection should be part of differential diagnosis of febrile illness in patients undergoing HSCT, and biopsy should be a standard practice of early diagnosis in these patients.

Se presenta el caso clínico de una niña de 10 años, con una leucemia linfoblástica aguda en recaída, sometida a un trasplante de progenitores hematopoyéticos (TPH) haploidéntico, con enfermedad injerto contra hospedero cutánea y digestiva grado II, en tratamiento con corti-costeroides y ciclosporina, que presentó el día +54 posttrasplante fiebre y compromiso de estado general. Dentro del estudio de su cuadro febril se practicaron imágenes que mostraron presencia de nódulos pulmonares y hepáticos. Se realizó una biopsia hepática cuyo estudio incluyó histología, tinciones y cultivo para bacterias y hongos. La tinción de Ziehl Nielsen de tejido hepático, así como las baciloscopias de contenido gástrico, aspirado traqueal y de fluido bronquial obtenido por lavado broncoalveolar (LBA) fueron positivas. El informe definitivo de cultivo confirmó Mycobacterium tuberculosis en contenido gástrico, esputo, LBA y tejido hepático, sensible a rifampicina, isoniazida, estreptomicina y etambutol, con determinación de mutaciones de genes rpoβ y kat G (-). Se confirmó el diagnóstico de tuberculosis, por lo que recibió tratamiento diario con cuatro fármacos por dos meses y luego terapia trisemanal con rifampicina, isoniazida y etambutol por nueve meses. Controlada por los equipos de trasplante, infectología y broncopulmonar, la paciente se mantiene actualmente en buenas condiciones generales, con imágenes con resolución del compromiso hepático y pulmonar y baciloscopias negativas. La infección por M. tuberculosis debe formar parte del diagnóstico diferencial de los cuadros febriles en los pacientes sometidos a TPH, y la toma de biopsia debe ser una práctica habitual y precoz en el enfrentamiento diagnóstico de estos pacientes.

The association between single nucleotide polymorphism analysis of tryptophan hydroxylase isoform gene rs11178997 and depression and suicidal behavior / 中华行为医学与脑科学杂志

ObjectiveTo explore the relationship between single nucleotide polymorphism analysis of a novel tryptophanhydroxylase isoform(TPH2)gene rs11178997and depression,and suicidal behavior.MethodsThe specimens of peripheral blood were collected from Chinese Northern 300 depression and 300 controis.The amplification of TPH2 gene rs11178997 was executed by realtime-polymerase chain reaction (realtime-PCR),and analyzed by directed sequencing.And the association between the polymorphisms of TPH2 gene and depression and suicidal behavior was analyzed with SPSS 17.0.ResultsThe genotypic frequencies of the SNPs did not deviate from Hardy-Weinberg equilibrium both in patient and control groups (P ＞ 0.05 ).Compared with control group,significant difference of genotypes and alleles of TPH2 gene rs1 1178997 single nucleotide polymorphism had been found in patient group (75.7％ vs 39.7％,6.0％ vs 1.3％,18.3％ vs 1.3％ ; P＜ 0.05 for all),and the AA genotype frequency of rsl 1178997 was significantly higher in patients.Meanwhile there were not significant differences between genotypes of TPH2 gene rs11178997 and suicide behavior in patient group.Suicidal behavior of depression patients in allele genotypes was higher than nonsuicide behavior of depression patients (P ＞0.05).ConclusionTPH2 gene rs4570625 single nucleotide polymorphisms have association with the susceptibility of depression.

Laterodorsal Tegmentum and Pedunculopontine Tegmental Nucleus Circuits Regulate Renal Functions: Neuroanatomical Evidence in Mice Models / 华中科技大学学报（医学）（英德文版）

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney.In this study,we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse.PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg,and themiddle and caudal parts of PPTg after tracer injection in the kidney.PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg,whereas PRV-614/TH neurons were scattered within the three parts of LDTg.PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg).These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.

Comparison of biostimulation and bioaugmentation techniques for the remediation of used motor oil contaminated soil

This study was carried out on the bioremediation of used motor oil contaminated soil artificially contaminated to a pollutant level of 40,000ppm using biostimulation and bioaugmentation remediation techniques for 42 days. Four treatment options were investigated in wooden microcosms: Control (T1), water amended (T2), biostimulation (T3) and hybrid of biostimulation and bioaugmentation (T4). The effectiveness of bioremediation processes were monitored using the total petroleum hydrocarbon removal (TPH) and total bacterial count (TBC). T3 had the highest TPH removal rate (69.2±0.05 percent), followed by T4 (65.2±0.25 percent) and T2 (58.4±0.5 percent); the control (T1) had the lowest TPH removal rate (43.2±1.5 percent). TBC revealed that bioremediation actually took place; T4 had the highest maximum bacterial growth of 9.6E+07CFU/g, followed by T3 (7.2E+07CFU/g), T2 (1.7E+05CFU/g) and T1 (1.65E+05CFU/g). In addition, T3 had the highest metal removal rate (2.172 percent) and T4 had the lowest metal removal rate (0.203 percent).

O presente estudo trata da biorremediação usandose solo contaminado artificialmente com óleo de motor a um nível de poluente de 40.000 ppm usando técnicas de remediação por bioestimulação e por bioagumentação durante 42 dias. Quatro opções de tratamento foram investigadas no microcosmo de madeira: Controle (T1), água alterada (T2), bioestimulação (T3) e híbrido de bioestimulação e bioaugmentação (T4). A eficácia dos processos de biorremediação foram monitoradas usando a remoção de hidrocarbonetos totais petróleo (TPH) e contagem bacteriana total (TBC). T3 teve a maior taxa de remoção de TPH (69,2 ±; 0,05 por cento), seguido por T4 (65,2 ±; 0,25 por cento) e T2 (58,4 ±; 0,5 por cento); o controle (T1) apresentou a menor taxa de remoção de TPH (43,2 ±; 1,5 por cento). TBC revelou que a biorremediação efectivamente ocorreu; T4 teve o maior crescimento de bactérias 9,6E+07CFU/g, seguido pelo T3 (7.2E+07CFU/g), T2 (1.7E+05CFU/g) e T1 (1.65E+05CFU/g). Além disso, T3 apresentou a maior taxa de remoção metal (2,172 por cento) e T4 teve a mais baixa taxa de remoção metal (0,203 por cento).

Association Between Suicide Attempts in Patients With Depressive Disorder and Tryptophan Hydroxylase A218C Polymorphism / 신경정신의학

OBJECTIVES: Several lines of evidence suggest the serotonergic dysfunction involved in the biological susceptibility of suicide. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin, plays a vital role in serotonin metabolism. In a case-control study, we investigated whether the TPH gene was a susceptible factor for suicidal behavior in depressive patients. METHODS: The subjects were 218 depressed patients who attempted suicide and visited emergency rooms in multi-medical centers. One hundred thirty hospitalized non-suicidal depressed patients and the 161 normal controls were matched with the suicidal group. Individuals in all 3 groups were evaluated independently by a Structured Clinical Interview for the purpose of establishing a DSM-IV criteria diagnosis (SCID). The severity of depressive symptoms was evaluated using Hamilton depression rating scale (HDRS). RESULTS: There was no significant difference in genotype distributions and allele frequencies of TPH intron 7 A218C polymorphisms among 3 groups. Furthermore, no significant difference in genotype counts and allele frequencies of the polymorphisms was found among lethal suicidal depressed patients, non-suicidal depressed patients and the normal controls. CONCLUSION: This study suggests that the A218C polymorphism of the TPH gene is unlikely to have a major effect on the susceptibility of suicidal behaviors in depressive patients.

The Genetic and Psychosocial Factors Affecting the Change of Drinking Behavior of Male College Students / 신경정신의학

OBJECTIVES: This study aimed to determine the general predictive factors of change in drinking behavior and to provide materials for preventing drinking problems during early adulthood through examining genetic and psychosocial factors affecting the change of drinking behavior in college students. METHODS: The subjects were 101 male college students, a part of 534 students who had completed the previous study in 2000. In the present study as a 6-years follow up, we reassessed the drinking pattern and psychosocial variables and compared the results with previous data of the same subjects. To identify factors affecting the current drinking pattern, we used stepwise multiple regression and logistic regression analysis. RESULTS: D allele (ALDH2) was found to reduce the degree of drinking and suppress problematic drinking, and C allele (TPH) had a suppression effect on problematic drinking. Drinking motive had a direct effect on the degree of drinking and problematic drinking. Negative cognitive expectancy had a direct effect on problematic drinking. CONCLUSION: Authors found some factors affecting the change of alcohol drinking behavior in college students and confirmed that there were hierarchies of significance among these factors. These may be applicable as variables for predicting drinking behavior in early adulthood.

The Tryptophan Hydroxylase A218C Polymorphism in Patients with Bipolar Disorder / 대한정신약물학회지

OBJECTIVE: This study has been carried out to explore the genetic causes of bipolar disorder by comparing the frequency of Tryptophan Hydroxylase (TPH) A218C polymorphism between bipolar disorder patients and normal controls, and to explore the relation between clinical characteristics of bipolar disorder patients and TPH polymorphism. METHODS: The genotype and allele frequencies of TPH in the genome of 113 hospitalized patients with bipolar disorder was compared with those of 124 normal control subjects using polymerase chain reaction and restriction fragment length polymorphism. The association between TPH A218C polymorphism and clinical characteristics in bipolar disorder patients were explored. RESULTS: The distributions of TPH A218C polymorphism between the patients with bipolar disorder and normal control subjects show no difference statistically. There was a significant difference in the distribution of TPH genotype by clinical characteristics. The frequency of C allele is significantly higher in patients with a history of suicidal attempts. The frequency of A allele is significantly higher in patients with family history of bipolar disorder. CONCLUSION: This study suggests that suicidal attempts and family history in the patients with bipolar disorder are clearly associated with TPH A218C polymorphism and may explain, in part, the biological basis for these typologies.

Effects of Chronic Alcohol Exposure on Dopaminergic and Serotonergic Neurotransmission System in Rat / 대한정신약물학회지

OBJECTIVE: This study investigates the effects of chronic alcohol exposure on rat brain THmRNA expression, TH (tyrosine hydroxylase) acitivity, and TPH (tryptophan hydroxylase) activity which are important in synthesis of dopamine and serotonin and other components of both the dopaminergic and serotonergic systems of the rat brain. METHODS: Rats were fed a liquid diet containing alcohol for 4 weeks. We investigated effects of chronic alcohol exposure on dopaminergic systems as follows. We evaluated expression of THmRNA in LC, VTA and substantia nigra by using in-situ hybridization and measured activity of TH by using immunoassay. We used HPLC for simultaneous measurement of dopamine, DOPAC and HVA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. Also we investigated serotonergic systems as follows. We evaluated expression of TH mRNA in the dorsal raphe nucleus by using radioprobe and measured the activity of TPH by using enzyme immunoassay. We used HPLC for simultaneous measurement of 5-HT and 5-HIAA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. RESULTS: Alcohol exposure for 4 weeks increased the expression of TH mRNA in the ventral tegmental area and the locus ceruleus but not in the substantia nigra. The 4 weeks of alcohol exposure did not cause significant changes in levels of dopamine and metabolites in the different areas of the brain, nor was it associated with changes in the maximal binding and affinity (Kd) of anterior striatal dopamine D2 receptor. Alcohol exposure for 4 weeks had no effect on the expression of TPH mRNA or on the activity of TPH in the dorsal raphe nucleus and the hypothalamus. CONCLUSION: We reported at first that chronic alcohol exposure could increase TH mRNA in the locus ceruleus. In a previous study of acute alcohol treatment, there is increase of dopamine metabolism but in this study, we did not observe any changes in dopamine metabolism in the different areas of the brain. Also we did not see any significant changes in the synthesis and metabolism of serotonin after 4 weeks of chronic alcohol exposure compared with control. Therefore, synthesis and metabolism of serotonin was affected in the acute phase. And, as previous reports have suggested, any changes caused by alcohol returned to previous levels via adaptation and regulatory mechanisms.

Effects of Psychosocial Factors and the Genotypes of Aldehyde Dehydrogenase II and Tryptophan Hydroxylase on the Alcohol Use in Freshmen of a University / 대한정신약물학회지

OBJECTIVE: This study was done to investigate the genetic polymorphism of Aldehyde Dehydrogenase (ALDH) II and Tryptophan Hydroxylase (TPH) and examine effects of socio-demographic, psychological and genetic factors on the alcohol use in freshmen of a university in Korea. METHODS: ALDH II (N=534) and TPH (N=504) genotypes of 551 subjects were analyzed using polymerase chain reaction and restriction fragment length polymorphism method. The severity of alcohol drinking was assessed by average alcohol use per drinking episode and frequency of drinking per month. Characteristics of alcohol related behaviors, socio-demographic information, and motives and expectancies of drinking in the subjects, were assessed by designed questionnaires and selfreport scales. RESULTS: The frequencies of NN, ND, and DD genotype of ALDH II (N=534) were 64.0%, 30.1%, and 5.8%, while those of AA, AC, and CC genotypes of TPH (N=504) were 31.7%, 48.4%, 19.8% respectively. The distribution of ALDH II genotypes was not correlated with that of TPH genotypes. Subjects with D (-) (NN) genotype showed more average alcohol use per drinking episode (chi2 trend=29.42, p=0.001) and higher severity index of alcohol drinking (F=9.36, df=2, p=0.000) compared with those with D (+) (ND or DD) genotypes. Subjects with D (-) genotype showed higher frequency of heavy drinking behavior (chi2 trend=5.25, p=0.022) and blackout episode (chi2 trend=17.84, p=0.001). Socio-demographic, psychological, and genetic factors seemed to contribute to the severity of alcohol drinking in the subjects. CONCLUSIONS: C allele of TPH genotypes is important in determining the severity of drinking in subjects with NN genotype of ALDH II. Social motive, gender, and D allele of ALDH II genotype are contributing factors to determine the severity of drinking in total subjects. D allele of ALDH II genotypes plays an important role in determining the severity and motives of drinking, and other alcoholrelated behaviors.

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.

Effect of Hypophysectomy on Monoamine-synthesizing Enzyme Activities in Rat Brain and Adrenal Gland / 대한정신약물학회지

In an attempt to investigate the regional specificity of effect of pituitary hormones on the activities of tyrosine hydroxylase(TH) and tryptophan hydroxylase(TPH), which are the rate-limiting enzymes in catecholamine and serotonin biosyntheses, respectively, the authors measured enzyme activities after hormonal deprivation, using the hypophysectomized animal model. The results are summarized as follows. First, whereas body weights of sham-operated group were increased gradually over time, those of hypophysectomized group were little changed. Second, the change of TH activity between sham-operated and hypophysectomized groups was not observed in each region of brain. Third, the change of TPH activity between two groups also was not observed in dorsal raphe nucleus and hypothalamus. It appears from the above findings that neural stimuli may be much more significant in the maintenance of normal level of TH and TPH in the brain than hormonal stimuli, and endocrine hormones might not directly affect monoaminergic neurotransmission in the absence of stress.