Current state of monoamine oxidase A in prostate cancer / 国际外科学杂志

Recent years, the incidence of prostate cancer is increasing, and the need of novel and effective diagnosis and treatment for prostate cancer is becoming more and more urgent.Monoamine oxidase A (MAO-A) is a mitochondrial binding enzyme, which plays an important role in the deamination of some neurotransmitters. Currentlly, some novel studies have shown that MAO-A plays an important role in the occurrence, development and metastasis of prostate cancer. At present, MAO-A has become a potential therapeutic target of prostate cancer and has been widely concerned. This article make a review on the possible mechanism of MAO-A in the occurrence, development and metastasis of prostate cancer and the application of MAO-A in the diagnosis and treatment of prostate cancer.

Postpartum depression: association with genetic polymorphisms of noradrenaline metabolic enzymes and the risk factors / 南方医科大学学报

OBJECTIVE@#To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section.@*METHODS@#A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors.@*RESULTS@#The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression.@*CONCLUSIONS@#The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.

Association study of the polymorphism of MAOA gene with panic disorder / 中华行为医学与脑科学杂志

Objective To explore the association between monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism and panic disorder,and then to compare panic disorder(PD) severity patient with different MAOA VNTR genotypes.Methods The structured clinical interview for the diagnostic and statistical manual of mental disorders fourth edition (DSM-Ⅳ) Axis I Disorders (SCID-1) was administered by a trained clinical psychiatrist,135 patients with PD and 195 healthy controls were recruited.MAOA-VNTR polymorphism were measured by fluorescent tags amplification product length polymorphism technology,Chi-square test was used to compare the distribution difference between each genotype and the allele frequency distribution.Results ①Whether male or female,there was no statistically significant difference between case group and healthy control group in the genotype and allele frequencies of MAOA-VN-TR polymorphism (x2=1.574,1.894,3.588;all P＜0.05).② There was no statistically significant difference between genotypes and panic disorder severity in the male with panic disorder ((14.46± 3.53),(14.15 ± 4.02);t=-0.247,P＞0.05).③)However,there was significant difference between genotypes and panic disorder severity in the female with panic disorder((13.15±3.47),(16.57±4.34),(15.27±4.91);F=4.222,P＜ 0.05).MAOA VNTR-L/L carriers experienced more serious panic (16.57 ± 4.34) than the patient with MAOA VNTR-H/H (13.15±3.47) (P＜0.01) by LSD multiple test.Conclusion No association between MAOA-VNTR polymorphism and panic disorder is found in Chinese Han population,but low activity homozygous genotype may be related to the severity of panic disorder in female patient with panic disorder.

Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder

OBJECTIVE: Impulsivity is a core feature of borderline personality disorder (BPD) and antisocial personality disorder (ASPD) that likely arises from combined genetic and environmental influences. The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations. Although impulsivity is a risk factor for aggression in BPD and ASPD, little research has investigated potential gene-environment (G×E) influences impacting its expression in these conditions. Moreover, G×E interactions may differ by diagnosis. METHODS: Full factorial analysis of variance was employed to investigate the influence of monoamine oxidase-A (MAO-A) genotype, childhood abuse, and diagnosis on Barratt Impulsiveness Scale-11 (BIS-11) scores in 61 individuals: 20 subjects with BPD, 18 subjects with ASPD, and 23 healthy controls. RESULTS: A group×genotype×abuse interaction was present (F(2,49)=4.4, p=0.018), such that the interaction of MAOA-L and childhood abuse predicted greater BIS-11 motor impulsiveness in BPD. Additionally, BPD subjects reported higher BIS-11 attentional impulsiveness versus ASPD participants (t(1,36)=2.3, p=0.025). CONCLUSION: These preliminary results suggest that MAOA-L may modulate the impact of childhood abuse on impulsivity in BPD. Results additionally indicate that impulsiveness may be expressed differently in BPD and ASPD.

Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice

We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy--dimethyltryptamine (5-MeO-DMT)-induced hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited hyperthermia were attributable to the loss of heat through the activation of 5-HTreceptor and thermogenesisthe stimulation of 5-HTreceptor, respectively. Thus serotonergic 5-MeO-DMT-induced hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SCvalue (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.

Different brain activity in pons in adolescent males with high-and low-activity MAOA genotype: resting-state fMRI study / 中华行为医学与脑科学杂志

Objective To examine the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents.Methods Resting-state fMRI was performed on 31 healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H).The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software,and was compared between two genotype groups.The region ROIs showed significant difference.The ALFF data in ROIs were related to BIS scores.Results Compared with the MAOA-H group,the MAOA-L group showed a significant decrease of ALFF (P＜0.001) in the pons (MNI coordinates:-6,-19,-23;6,-16,-17;-6,-25,-32).In addition,the BIS scores were positively correlated with ALFF in pons in the MAOA-L group (r=0.398,P=0.02),but not in the MAOA-H group.Conclusions There exists relevance between the polymorphism of MAOA and the spontaneous brain activity in pons.And the lower activity of spontaneous brain activity in pons may be a key risk factor for impulsivity and aggression.

Correlation study on susceptible genes of obsessive compulsive disorder of Han population in northeast China / 中华行为医学与脑科学杂志

Objective To explore the relationship between Monoamine oxidase A (MAOA) receptor gene,catechol-O-methyltransferase (COMT) receptor gene,dopamine D3 receptor(DRD3) gene and 5-HT2C receptor gene(5-HT2c) of Han population in northern China and obsessive compulsive disorder.Methods Polymerase chain reaction amplification determination of MAOA-T1460C,COMT-Val158Met,DRD3-Ser9Gly,5-HT2c-C ys23Ser four loci receptor gene polymorphism in 164 patients with OCD patients including 103 core pedigrees of fragment length polymorphism,and association and linkage disequilibrium (TDT)analysis.Results There was no significant difference of MAOA-T1460C,COMT-Val158Met,DRD3-Ser9Gly,5-HT2c-Cys23Ser four receptor gene in the patient group and the control group of genotype and allele distribution difference(P＞0.05),four receptor gene loci were in accordance with the balance of the H-W,the MAOA-T1460C receptor gene in female patients group and control group,the early group and control group,which has forced thinking and difference of compulsive behavior group and the control group,only the obsessional group and the control group of genotype and allele distribution was statistically significant(P＜0.05),and the family group between chain(P=0.0001) ;5-HT2c-Cys23Ser receptor gene in the case group and the control group,male both forced thinking and compulsive behavior group and control group differences in genotype and allele distribution was statistically significant (P＜ 0.05),and between family groups exist chain (P=0.0389) ; COMT-Val158Met receptor gene in the control experiments were no significant difference(P＞0.05),and with the house group does not exist between the chain (P=0.0622) ;DRD3-Ser9Gly receptor gene in the control experiments were no significant difference(P＞0.05),and with the family groups there is no chain(P=0.1101).Conclusion MAOA-T1460C receptor gene polymorphism and 5-HT2c-Cys23Ser receptor gene polymorphisms may be the susceptible gene of obsessive compulsive disorder.

The analysis on correlation between childhood physical abuse and monoamine oxidase A polymorphisms in domestic violence / 中国神经精神疾病杂志

Objective To investigate the effects of the interaction between environmental factors and monoamine oxidase A (MAOA) gene polymorphism in Han and Uygur on alcoholics in Xinjiang. Methods The data of childhood abuse and domestic aggressive behaviors were collected from 284 patients with alcohol dependence from Xinjiang using self-made questionnaires, Modified Overt Aggression Scale (MOAS) and Barratt Impulsivity Scale-11 (BIS-11). The meth?ods of PCR and DNA sequencing technique were conducted to detect rs1137070 single nucleotide polymorphism loci of MAOA gene. Logistic regression analysis was performed to adjust for interaction effects of gene and childhood abuse on domestic violence. Results The scale evaluation identified 143 patients with and 138 patients without domestic violence. Childhood abuse and gene were both risk factors in domestic violence. The interaction effect of childhood abuse with rs1137070 was significant. the relative excess risk, the interaction attribution ratio and the interaction index were 1.00,0.14 and 1.20, respectively. Conclusions The interactions between genes and environmental risk factors may contribute to the domestic violence in Han and Uygur on alcoholics in Xinjiang.

The moderating effect of monoamine oxidase A gene polymorphism in relationship between childhood abuse of male adolescents and externalizing behaviors / 中华行为医学与脑科学杂志

ObjectiveTo explore the relationship between male adolescents' childhood abuse and externalizing behaviors,and the moderating effect of monoamine oxidase A (MAOA) gene promoter region variable number tandem repeat (VNTR) polymorphism.MethodsThrough random cluster sampling,352 Han male middle school students from Changsha were tested by Achenbach child behavior checklist-youth self reports (CBCL-YSR)and childhood trauma questionnaire-28 item short form (CTQ-SF),their MAOA genotypes were also identified.A hierarchical multiple regression analysis was used to test the moderating effect.Results ( 1 ) Compared participates with high activity MAOA gene and that with low activity MAOA gene,there were no significant differences on age ( ( 15.82 ± 1.52) vs ( 15.94 ± 1.62 ) ),externalizing behaviors ( ( 15.13 ± 10.14 ) vs ( 14.33 ± 9.70 ) ),total abuse ( (52.59 ± 10.46) vs (51.39 ± 7.56 ) ),emotional abuse( ( 7.63 ± 3.31 ) vs ( 7.11 ± 2.68 ) ),physical abuse ( ( 6.40 ± 2.82) vs (6.12 ± 2.05 ) ),sexual abuse ( ( 6.42 ± 3.24 ) vs ( 5.94 ± 1.72 ) ),emotional neglect ((13.44±5.12) vs (13.16 ±4.83) ),physical neglect( (10.27 ±2.64) vs (10.44±2.53))(t=-1.789～0.678,P ＞ 0.05 ).(2)Except emotional neglect and physical neglect,emotional abuse,physical abuse and sexual abuse could predict externalizing behaviors( Sβ =0.141 ～0.347,P ＜ 0.01 ).(3) MAOA gene was not directly related to externalizing behaviors( Sβ =- 0.023,P ＞ 0.05 ).There was a significant interaction between MAOA gene and emotional abuse( Sβ =-0.148,P ＜ 0.01 ).The interaction between MAOA gene and physical abuse or sexual abuse showed no statistical significance( Sβ =- 0.067,- 0.005,P ＞ 0.05 ).ConclusionMAOA gene polymorphism can moderate the relationship between male adolescents'childhood emotional abuse and externalizing behaviors.

Influence of monoamine oxidase A gene and brain function in the dynamic facial expression recognition in depressed patients / 中华行为医学与脑科学杂志

Objective To explore the impact of the variable number of tandem repeats of monoamine oxidase A gene (MAOA-uVNTR) on the intensity of brain activation during the recognition of facial expression in patients with depression and healthy controls.Methods 28 cases of depression,as well as 33 healthy controls who were matched in gender, age and years of education were divided into different genotypes with the methods of polymerase chain reaction (PCR) amplification and 1.5% agarose gel electrophoresis separation.61 cases were scanned to compare the intensity of brain activation in the recognition of happy, sad and neutral facial expression.Results In healthy controls,cases with high-activity genotype showed increased activation in left cuneus,left inferior frontal gyrus, right medial frontal gyrus and left inferior parietal lobule in comparision with carriers of low-activity genotype.In the depressed, compared with patients with low-activity genotype, cases with high-activity genotype decreased activation in bilateral putamen, left postcentral gyrus, left fusiform gyrus, right superior temporal gyrus and right thalamus.Conclusion Healthy controls with high-activity genotype shows the trend of priority for the identification of negative emotion,this genotype may be one of the risk factors for normal people suffering from depression.Patients with high-activity genotype is associated with the inhibitory of positive emotional state, this may attribute partly to the emotional symptoms in such kind of patients more serious.

Association analysis of central executive function with the functional polymorphisms in monamime oxidase A and dopamine-β-hydroxylase / 中华行为医学与脑科学杂志

Objective To explore the associations of the sub-components of central executive function ( inhibition, shifting and updating) with monoamine oxidase A ( MAOA ) and dopamine-β-hydroxylase ( DBH ).Methods The cognitive performance of the 719 healthy individuals,who were selected randomly from an university in Xi' an,was assessed by the world wide used paradigms of central executive function. Then, a populationbased study was performed to analysis the associations of central executive function with the 30-bp variable number tandem repeat and -C1021T in the promoters of MAOA and DBH ,respectively. Results The results indicated that the 30-bp variable number tandem repeat of MAOA was associated with the performance of inhibition and updating ( x2 = 4.82,4.50; P= 0. 03,0.03 ) in males. The reaction time of inhibition test was shorter in 3r genotype group ( (671.32 ±9.77 )ms) than that in 4r genotype group ( (706.61 ± 14.58 ) ms) ,and the indivudals with 3r genotype (47.85 ±0. 69) had more updating numbers than the indivudals with 4r (45.13 ± 1. 05). However, there was no significant association of the -C1021T and DBH with the components of excutive function (P＞0.05). Conclusion The present study suggests that the 30-bp variable number tandem repeat of MAOA contributs to the inhibition in males while -C1021T of DBH has no striking effects on the components of executive function in males and females.

A preliminary study on the relationship of the monoamine oxidase A gene polymorphism and the gray matter concentration in patients with major depressive disorders / 中华行为医学与脑科学杂志

Objective To explore the impact of the variable number of tandem repeats of monoamine oxidase A gene (MAOA-uVNTR) on the concentration of gray matter in patients with major depressive disorders.Methods 56 cases of depression, as well as 37 healthy controls who were matched in gender, age and years of education were divided into low-activity genotype (3R or 3R/4R), and high-activity genotype (4R) with the methods of polymerase chain reaction (PCR) amplification and 1.5％ agarose gel electrophoresis separation. 93 cases all were performaned structural magnetic resonance imaging scanning. Results ① The difference of genotype and allele frequency between the depression group and the healthy group was not statistically significant(P＞0.05 ). ②Compared with the healthy,the concentration of gray matter( GMC ) of bilateral caudate nucleus (K = 11/68, Z =3.76/4.76 ), bilateral thalamus ( K = 21/181, Z = 3.26/3.63 ) and right hypothalamus ( K = 38/12, Z = 4.20/3.60) reduced significantly in depressed patients. ③ In patients with depression, cases with the high-activity genotype showed reduced GMC bilateral caudate nucleus (K = 17/33, Z = 3.23/4.36 ), left putamen ( K = 16, Z =3.42 ) and right hypothalamus( K = 12, Z = 3.62 ) in comparision with patients with low-activity genotype. In highactivity genotype group,compared with the healthy,patients with depression had reduced GMC in left caudate nucleus ( K = 11, Z = 4.13 ), bilateral thalamus ( K = 13/14, Z = 3.53/3.23 ) and left parahippocampal gyrus ( K = 13,Z = 4.04). Conclusion High-activity genotype may be an important factor contributing to the structural abnormalitily of the limbic-striatum-globus pallidus-thalamus loop.

Relationship between Obsessive-Compulsive Disorder and Monoamine Oxidase-A Genetic Polymorphisms in a Korean Population / 대한정신약물학회지

OBJECTIVE: There is increasing evidence that obsessive-compulsive disorder (OCD) is a multidimensional and heterogeneous disorder mediated by a range of different factors, including genetic variation. Our aim was to investigate the possible association of OCD with monoamine oxidase-A (MAO-A) gene polymorphisms in a Korean population. METHODS: Patients with OCD (N=121) and normal individuals (N=276) participated. Genomic DNA was extracted from the peripheral blood of all subjects, and genotypes were determined. Males and females were treated as separate groups because the MAO-A gene is located on the X chromosome. MAO-A genotypes and allele frequencies were compared with the Yale-Brown Obsessive-Compulsive Scale (YBOCS) factor scores of both groups. RESULTS: Male OCD patients exhibited a higher frequency of allele 3.00 and a lower frequency of allele 4.00 than did normal male patients. Additionally, male patients with allele 4.00 scored higher for YBOCS factor 1 (obsession: hoarding; compulsion: counting, repeating, hoarding, ordering) than did those with allele 3.00. CONCLUSIONS: The MAO-A gene may be associated with the development of OCD in males. Further study is necessary to evaluate the relationship between OCD and MAO-A genetic polymorphisms.