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Objetivo:Revisar e discorrer sobre os estudos científicos que buscam a associação do polimorfismo do gene MAOA, do tipo uVNTR, com distúrbios mentais em adultos. Método:Foi realizada uma revisão integrativa de acordo com o modelo PRISMA. A pesquisa seguiu as etapas de formulação da questão de pesquisa, seleção das bases de dados de busca de referências, definição da estratégia de busca, avaliação da elegibilidade dos estudos, triagem e seleção dos artigos, extração de dados e compilação dos resultados. Resultados:Foram selecionados 12 artigos originais que relataram o polimorfismo do tipo u-VNTR e seus alelos de 2, 3, 3,5, 4 e 5 repetições no gene MAOA, e sua associação com distúrbios psíquicos. Conclusão:O polimorfismo do gene MAOA do tipo uVNTR está relacionado com a funcionalidade da enzima MAOA, aumentando ou diminuindo sua atividade, elevando ou diminuindo os níveis de dopamina, serotonina ou noradrenalina, e essas alterações estão relacionados à diversos distúrbios mentais, como esquizofrenia, depressão, comportamentos agressivos antissociais, ansiedade, transtorno de déficit de atenção e hiperatividade (TDAH), transtorno do espectro autista e outros distúrbios relacionados à expressão desses neurotransmissores.
Objective: To review and discuss scientific studies that seek the association of the polymorphism of the MAOA gene, of the uVNTR type, with mental disorders in adults. Method: An integrative review was performed according to the PRISMA model. The research followed the stages of formulation of the research question, selection of reference search databases, definition of the search strategy, evaluation of the eligibility of studies, screening and selection of articles, data extraction and compilation of results. Results:We selected 12 original articles that reported the u-VNTR polymorphism and its alleles of 2, 3, 3.5, 4 and 5 repeats in the MAOA gene, and its association with psychic disorders. Conclusion: The polymorphism of the MAOA gene of the uVNTR type is related to the functionality of the MAOA enzyme, increasing or decreasing its activity, raising or decreasing the levels of dopamine, serotonin or noradrenaline, and these changes are related to several mental disorders, such as schizophrenia, depression, aggressive antisocial behaviors, anxiety, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder and other disorders related to the expression of these neurotransmitters.
Objetivo: Revisar y discutir estudios científicos que busquen la asociación del polimorfismo del gen MAOA, del tipo uVNTR, con trastornos mentales en adultos. Método:Se realizó una revisión integradora según el modelo PRISMA. La investigación siguió las etapas de formulación de la pregunta de investigación, selección de bases de datos de búsqueda de referencias, definición de la estrategia de búsqueda, evaluación de la elegibilidad de los estudios, selección y selección de artículos, extracción de datos y compilación de resultados. Resultados:Se seleccionaron 12 artículos originales que reportaron el polimorfismo u-VNTR y sus alelos de 2, 3, 3.5, 4 y 5 repeticiones en el gen MAOA, y su asociación con trastornos psíquicos. Conclusión:El polimorfismo del gen MAOA del tipo uVNTR está relacionado con la funcionalidad de la enzima MAOA, aumentando o disminuyendo su actividad, elevando o disminuyendo los niveles de dopamina, serotonina o noradrenalina, y estos cambios están relacionados con varios trastornos mentales, como esquizofrenia, depresión, conductas antisociales agresivas, ansiedad, trastorno por déficit de atención con hiperactividad (TDAH), trastorno del espectro autista y otros trastornos relacionados con la expresión de estos neurotransmisores.
Subject(s)
Polymorphism, Genetic , Central Nervous System DiseasesABSTRACT
Background: Historically in psychogenetic research the attention has been paid to describing personality traits of the carriers of some sole genotypes; but in this work the characteristic traits of carriers of catecholaminergic system MAOA and COMT genes' genotypes different combinations are presented. Methods: A psychodiagnostic toolkit included 7 types of inventories. Genotyping was conducted with the help of DNA extraction from the buccal epithelium cells with subsequent PCR diagnostics and 3 types of statistical processing. Results: It was shown that carriers of a highly active diplotype have the lowest level of aggressiveness and are inclined to cooperate in the conflict; carriers of the highly active genotype MAOA in combination with the heterozygous genotype COMT have an average level of aggressiveness and high rates of emotional lability; carriers of low-level MAOA in combination with heterozygous genotype COMT have the highest rates of motivation to achieve success and verbal aggression; carriers of low-level MAOA and highly active COMT are emotionally labile and non-aggressive. Conclusion: We conclude that male carriers of a low-active diplotype have the highest level of aggressiveness and disposition to addictive behavior, which may indicate the association of this diplotype in a sample of young Russian men with social disadaptation.
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Background: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) is a semisynthetic coumarin with MAO-A inhibitory activity and positive results in forced swimming and tail suspension test in mice, but until now, it has not been studied in other screening antidepressant models in mice and rats. Objectives: The aim of this work was to assess the serotonin like effect of FCS-304 in the 5-hydroxytryptophan (5-HTP) test in mice, in the behavioral despair test in rats, and in the reserpine test in rats. Methods: Potentiation of 5-HTP (100 mg/kg, i.p.), induced head twitches were assessed in mice, previously treated with FCS-304 (50-75-150 mg/kg, p.o.). The behavioral despair test was performed in rats treated with FCS-304, recording the immobility time attained by the animals subjected to forced swimming. Antagonism of reserpine-induced ptosis was examined in rats, assessing the level of palpebral closure. Imipramine (30 mg/kg, p.o.) and vehicle (canola oil) served as positive and negative controls, respectively. Results: FCS-304 significantly potentiated 5-HTP induced head twitches in mice, in a dose dependent manner. In rats, FCS-304 significantly decreased the immobility time in the behavioral despair test and antagonized reserpine induced ptosis. Conclusions: These results add support to propose that FCS-304 could elicit antidepressant effects related to MAO-A inhibitory activity.
Antecedentes: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) es una cumarina semisintética inhibidora de MAO-A con efectos positivos en las pruebas de nado forzado y suspensión por la cola en ratones, sin embargo, hasta ahora no se había estudiado en otros modelos de tamizado antidepresivo en ratones y ratas. Objetivos: el objetivo de este trabajo fue evaluar el efecto de tipo serotoninérgico de FCS-304 en la prueba de potenciación de 5-hidroxitriptofano (5-HTP) en ratones, y su respuesta en la prueba de desesperanza conductual en ratas y en la prueba de reserpina en ratas. Métodos: se evaluó la potenciación de las sacudidas de cabeza inducidas por 5-HTP (100 mg/kg, i.p.), en ratones tratados con FCS-304 (50-75-150 mg/Kg, v.o.). La prueba de desesperanza conductual se realizó en ratas tratadas con FCS-304, expuestas a nado forzado. El antagonismo de la ptosis palpebral inducida por reserpina se examinó en ratas determinando el grado de apertura ocular. Imipramina (30 mg/kg, v.o.) y el vehículo (aceite de canola, 0,1 mL/10 g), sirvieron como controles positivo y negativo, respectivamente. Resultados: FCS-304 incrementó significativamente el recuento de sacudidas de cabeza inducidas por 5-HTP en ratones, en función de la dosis. En ratas, FCS-304 fue efectiva para disminuir el tiempo de inmovilidad en la prueba de desesperanza inducida por nado forzado y el grado de ptosis palpebral inducido por reserpina. Conclusiones: estos resultados dan soporte para proponer que FCS-304 ejercería efectos de tipo antidepresivo relacionados con la inhibición de MAO-A.
Subject(s)
Humans , Rats , Serotonin Agents , 5-Hydroxytryptophan , Coumarins , Antidepressive AgentsABSTRACT
Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .
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Monoamine oxidase A (MAOA) can catalyze the degradation of a variety of amine neurotransmitter,including serotonin.The abnormalities of these neurotransmitter are closely associated with many psychiatric disorders.Studies have found that MAOA is polymorphic,with a low activity variant (MAOA-L),and a high activity variant (MAOA-H).In this review,through the studies of early stress on human and animal models,the effects of early stress and MAOA polymorphism on the behavior and emotional loop of individuals are analyzed.Analysis shows that,MAOA-L,versus MAOA-H,is more plastic.In early adverse environment,MAOA-L will increase the risk of adult violence,and in the early of energetically favorable environment will reduce the incidence of violence.Abnormality is more likely to occur in the emotional processing and cognitive function in the neural affective loop of individuals with MAOA-L,which makes them more environmentally susceptible than those with MAOA-H.
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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.
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Objective To examine the impact on impulsivity trait by monoamine oxidase A variable nucleotide tan?dem repeat (MAOA-VNTR) genotype and children’s abuse experience. Methods The self-reported questionnaire of Bar?ratt Impulsiveness Scale (BIS), Childhood Trauma Questionnaire (CTQ) were conducted in 403 normal Han female adoles?cents from north-west of China. The DNA were extracted from their venous blood sample and were genotyped for the MAOA-VNTR polymorphism. A linear regression model was used to investigate the main effects of MAOA-VNTR and children's abuse, and their interaction effect on impulsivity. Results The main effect of Children’s maltreatment experi?ence on trait impulsivity was significant (P0.05). Conclusion The MAOA-VNTR genotype may not be involved in the female adolescents’impulsivity traits related to childhood maltreat?ment.
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The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms.
Subject(s)
Adolescent , Humans , Asian People , Body Mass Index , Depression , DNA , JointsABSTRACT
Las Funciones Ejecutivas permiten organizar nuestro comportamiento, regular nuestras emociones y en general, nuestro comportamiento. Estas funciones van incrementando su complejidad conforme el organismo crece y madura, acorde a las demandas ambientales y al desarrollo neurológico de los lóbulos frontales principalmente, sin embargo existen distintas variables que favorecerían su óptima ejecución, como la enzima MAO-A encargada de metabolizar neurotransmisores como la serotonina, involucrada en la regulación de conductas impulsivas. Así como el Temperamento que facilita la capacidad de autoregular la propia conducta, inhibiendo los impulsos en presencia de demandas no solo cognitivas sino también emocionales. Mediante la aplicación de pruebas de Inhibición en niños en edad preescolar y tomando en cuenta estos factores se observó que aquellos niños con la variación de MAO-A de Baja actividad Transcripcional y un Temperamento de Autocontrol tendían a tener mejores resultados para inhibir sus conductas en favor de un mejor resultado en la pruebas; contribuyendo al propósito de analizar distintas variables que permitan un mejor desarrollo de las Funciones Ejecutivas.
The executive functions allow to organize our behavior, to regulate our emotions and in general terms, our behavior. This function increases its complexity when the organism grows up and matures, in accordance with the environment conditions and the forebrain's neurological development. Nevertheless, there are different variables that can help its optimal execution like the MAO-A, in charge of the metabolism of the neurotransmissors, like the serotonin, in charge of the impulsive manners. Like the Temperament that makes easier the capability to regulate the self-behavior, through the inhibition of the impulses when the demands are not only cognitive, also with the emotional demands. With the application of the inhibition's tests in preschoolers children and these factors like reference. It was possible to watch that the preschoolers children with a low metabolic activity in the MAO-A and a self-control temperament, have developed a better results to inhibit their behavior in order to have a better result in the tests; this, represents a contribution to the purpose to analyze different variables that allow a better development of this executive functions.
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Entre los diversos factores asociados con la predisposición a la conducta violenta se encuentra la portación de alelos de riesgo. Para investigar el efecto de dos alelos de riesgo (baja actividad de MAO-A y 7 repeticiones DRD4) sobre mediciones de agresión, se evaluaron mediante escalas psicológicas a 60 hombres sanos. Los resultados indicaron que tanto el efecto principal de cada uno de los alelos de riesgo, como su interacción impactan sobre mediciones de hostilidad, enojo, impulsividad, empatía y rasgos antisociales de psicopatía. Se concluye que es necesario investigar el efecto de estos alelos sobre la estructura y función cerebrales, además estos alelos aparentemente confieren riesgo para el desarrollo de conductas violentas.
Among the factors associated with the predisposition to violent behavior is the bearing of risk alleles. To investigate the effect of two risk alleles (low activity of MAO-A and 7 repeat DRD4) 60 healthy men were assessed on psychological scales of aggression. The results indicated that both the main effect of each of the risk alleles, and their interaction impact on measures of hostility, anger, impulsivity, empathy and antisocial traits of psychopathy. We conclude that it is necessary to investigate the effect of these alleles on brain structure and function; these alleles apparently also confer risk for the development of violent behavior.
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INTRODUÇÃO: Muitos estudos têm investigado a associação do polimorfismo VNTR (número variável de repetições em série) localizado na região promotora do gene da enzima monoamina oxidase A (MAOA) com alterações no comportamento humano e em diversos transtornos psiquiátricos. OBJETIVO: O objetivo do presente trabalho foi revisar a literatura sobre a participação desse polimorfismo funcional na modulação do comportamento humano para o desenvolvimento dos transtornos psiquiátricos. MÉTODO: A pesquisa foi realizada na literatura em inglês, de janeiro de 1998 a junho de 2009, disponível no Medline, Embase, Web of Science e na base de dados PsycInfo, utilizando os seguintes termos: "MAOA e comportamento humano" e "MAOA e psiquiatria". RESULTADOS: Foram encontrados 3.873 estudos. Desses, 109 foram selecionados e incluídos na revisão. Encontrou-se associação de alelos de baixa atividade do VNTR com transtorno de personalidade antissocial, transtorno de conduta, transtorno de déficit de atenção e hiperatividade, jogo patológico e dependência de substâncias. Alelos da alta atividade da MAOA foram associados a depressão, ansiedade, neuroticismo e anorexia nervosa. Não se encontrou associação entre polimorfismos da MAOA e esquizofrenia e transtorno bipolar. CONCLUSÃO: Os principais achados dão suporte ao papel do polimorfismo VNTR da região promotora do gene da MAOA em alguns transtornos psiquiátricos, apesar das divergências encontradas devidas às dificuldades metodológicas de estudos em genética. De modo geral, os estudos associam os alelos de baixa atividade da MAOA com comportamentos impulsivos e agressivos ("comportamentos hiperativos"), enquanto os alelos de alta atividade do gene são mais associados a "comportamentos hipoativos".
INTRODUCTION: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. OBJECTIVE: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. METHOD: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". RESULTS: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. DISCUSSION: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.