Monoamine Oxidase A Gene Research Articles

A synonymous mutation of rs1137070 cause the mice Maoa gene transcription and translation to decrease.

The Monoamine Oxidase-A (MAOA) EcoRV polymorphism (rs1137070) is a unique synonymous mutation (c.1409 T > C) within the MAOA gene, which plays a crucial role in Maoa gene expression and function. This study aimed to explore the relationship between the mouse Maoa rs1137070 genotype and differences in MAOA gene expression. Mice carrying the CC genotype of rs1137070 exhibited a significantly lower Maoa expression level, with an odds ratio of 2.44 compared to the T carriers. Moreover, the wild-type TT genotype of MAOA demonstrated elevated mRNA expression and a longer half-life. We also delved into the significant expression and structural disparities among genotypes. Furthermore, it was evident that different aspartic acid synonymous codons within Maoa influenced both MAOA expression and enzyme activity, highlighting the association between rs1137070 and MAOA. To substantiate these findings, a dual-luciferase reporter assay confirmed that GAC was more efficient than GAT binding. Conversely, the synonymous mutation altered Maoa gene expression in individual mice. An RNA pull-down assay suggested that this alteration could impact the interaction with RNA-binding proteins. In summary, our results illustrate that synonymous mutations can indeed regulate the downregulation of gene expression, leading to changes in MAOA function and their potential association with neurological-related diseases.

Abstract We096: Gene therapy of MAOA fine-tunes nuclear cAMP nanodomain and improves cardiac hypertrophy in mice

Cardiac hypertrophy, a precursor to heart failure, represents a leading cause of global mortality and morbidity. Current therapeutic strategies focused on reducing the heart's workload, demonstrate limited efficacy. Nuclear-localized cAMP emerges as a promising therapeutic target, intervening in hypertrophic gene transcription and exhibiting overactivation in hypertrophic cardiomyocytes. Despite its potential, the spatiotemporal regulation and molecular targets of nuclear-localized cAMP (NLS-cAMP) remain elusive. Employing super-resolution imaging, we identified a pool of β1 adrenergic receptors (β1AR) at the nuclear envelope that transduces NLS-cAMP-PKA signaling in cardiomyocytes. Utilizing a nuclear-localized FRET biosensor, our investigations revealed that the deletion or inhibition of monoamine oxidase A (MAOA) amplifies the norepinephrine-induced NLS-β1AR activation signal. Conversely, overexpressing MAOA prevents NLS-B1AR activation, underscoring the critical role of MAOA in regulating the NLS-cAMP nanodomain. Single-cell transcriptome analysis unveiled a decline in MAOA expression in a mouse cardiac hypertrophy model. Cardiac-specific deletion of MAOA in mice led to simultaneous hypertrophy and eventual heart failure. Mechanistically, MAOA deletion increased PKA-dependent phosphorylation of HDAC1, H3K27 acetylation, and chromatin accessibility of hypertrophic genes, including Nppa and Nppb. To validate therapeutic potential, we intraventricularly injected adeno-associated virus (AAV) 9 vectors expressing mcherry or mcherry-MAOA under the control of the cTNT promoter into mice. Inducing cardiac hypertrophy through Angiotensin II infusion five weeks later, mice preinjected with AAV-MAOA exhibited attenuated cardiac hypertrophy and improved cardiac function. Our findings suggest that MAOA gene therapy holds promise for treating hypertrophy by specifically targeting the NLS-cAMP nanodomain, opening new avenues for targeted interventions in cardiac hypertrophy and heart failure.

Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of Plasmodium vivax malaria relapses.

Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses. Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses. The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active. We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite.

Association between serum catecholamine levels and VNTR polymorphism in the promoter region of the monoamine oxidase A gene in forensic autopsy cases

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.

Usability of MAO-A gene in the judicial process

Monoamine oxidase (MAO-A) is an enzyme found in the nervous system and plays an important role in the breakdown of monoamine neurotransmitters. This enzyme varies among individuals depending on genetic factors. The monoamine oxidase-A (MAO-A) gene has been studied by various researchers to understand behavioral differences between individuals and evaluate crime propensity. However, serious ethical and legal problems may arise regarding the use of genetic factors alone in the judicial process. In this context, considering environmental factors as well as the MAO-A gene may contribute to the development of a more comprehensive approach. The role of the MAO-A gene in the judgment process has created an area of research that allows us to understand behavioral differences. The MAO-A gene has been associated with various behavioral traits. It has particular effects on aggressive behavior, antisocial behavior, and emotional reactions. In this context, the MAO-A gene may be an important factor in determining how individuals respond to environmental factors and guide their judgment processes. Some studies show that individuals with low MAO-A activity may be prone to antisocial behavior and crime. Thus, the MAO-A gene can be taken into consideration in determining guilt in legal processes. Assessing individuals' criminal propensity based on genetic factors can make the justice system more effective and fair. For example, harsh childhood conditions or traumatic experiences can trigger genetic predispositions and increase criminal propensity. In this case, it is important to take environmental factors into account when evaluating the genetic profile of the individual during the judicial process. Many ethical and legal issues need to be carefully considered on how to integrate the MAO-A gene into the judicial system. Therefore, research on the usability of the MAO-A gene in the judicial process should be continued.

Analysis of the Relationship Between MAOA and CDH-13 Genes and Crime

When scholars investigate criminal behaviour, they observe the existence of several criminal organizations characterized by a continuous involvement in illegal activities over successive generations. There is a potential hereditary transmission of criminal conduct. The topic of heredity invariably encompasses the issue of chromosomes and genes, as these elements are essential to the process of heredity. Currently, there is a lack of empirical evidence supporting the notion of criminal genes, and the consensus among scholars in the field of criminal psychology is that criminal behaviour is a multifaceted outcome influenced by physiological, social, and psychological factors. In contemporary times, within the framework of the expeditious advancement of science and technology, there has been a corresponding escalation in the incidence of criminal activities. Researchers have extensively investigated potential connections or shared characteristics among individuals involved in criminal activities across numerous situations. Scientists have directed their attention on genes, seeing them as the fundamental basis of emerging biotechnologies. This research employs a literature review and analysis method to provide a succinct description of the association between the MAOA (Monoamine oxidase A) and CDH-13 (Cadherin-13) genes and criminal behaviour. Furthermore, it examines specific instances to investigate the potential role of genetic factors in contributing to criminal tendencies.

Association of two variable number of tandem repeats in the monoamine oxidase A gene promoter with suicide completion: The present study and meta-analysis.

One potential cause of suicide is serotonergic dysfunction. Sex differences have been reported to modulate the effects of serotonergic polymorphisms. Monoamine oxidase A (MAOA) is an enzyme that degrades serotonin and is located on the X chromosome. A previous study indicated that the upstream (u) variable number of tandem repeat (VNTR) in the MAOA gene promoter may be associated with suicide. However, a meta-analysis showed that this polymorphism may not be related to suicide. According to a recent study, compared with the uVNTR, the distal (d)VNTR and the haplotypes of the two VNTRs modulate MAOA expression. We examined the two VNTRs in the MAOA gene promoter in 1007 subjects who committed suicide and 844 healthy controls. We analyzed the two VNTRs using fluorescence-based polymerase chain reaction assays. We conducted a meta-analysis for the two VNTRs to update it. Our results demonstrated that neither the genotype-based associations nor allele/haplotype frequencies of the two VNTRs were significantly associated with suicide. In the meta-analysis, we did not indicate relationships between uVNTR and suicide nor did we identify articles analyzing dVNTR in suicide. Overall, we did not find a relationship between the two VNTRs in the MAOA promoter and suicide completion; thus, warranting further studies are required.

Outpatient management of REM sleep behavior disorder case in Brunner syndrome

IntroductionBrunner syndrome is a recessive X-linked disorder characterized by impulsive aggressiveness and mild mental retardation associated with Monoamine Oxidase – A (MAOA) deficiency (Brunner et al. Science 1993; 262 578-580).ObjectivesTo present a REM sleep behavior disorder (RBD) case in a patient with Brunner syndrome.MethodsThe present study is a case report of a patient followed in our hospital’s outpatient care. We also searched for previous case reports of sleep disorders and other clinical features in Brunner syndrome using a pubmed query.ResultsA 46-year-old Spanish male, diagnosed with Brunner syndrome due to the mutation c.1438A>G/iVS14-2 A>G, a loss-of-function mutation in the X-linked MAOA gene. He suffers from mild mental retardation and psychotic disturbances treated with SSRI and antipsychotic drugs. The patient was referred to our outpatient care to assess his sleep abnormal behaviors. He had been presenting with episodes of sleep-related vocalization and complex motor behaviors during sleep for the last 3 years, correlating with dream mentation. His relatives recounted episodes of talking, screaming, gesturing, kicking, falling out of bed and crying during sleep. Dream content referred by the patient was often related to persecutions, attacks and fights.Polysomnography revealed vocalization and gesticulation during REM sleep compatible with the diagnosis of RBD. The addition of clonazepam to his treatment at doses of 1-3 mg per day achieved significant clinical response of the sleep disorder.ConclusionsThe clinical presentation suggested the diagnosis of RBD case in a patient with Brunner syndrome. Although sleep disorders are not one of the most important or frequent clinical features in Brunner syndrome, they are described in the literature and can significantly affect the patient’s quality of life. To our knowledge, this is the first report about clinical management of RBD case in Brunner syndrome.Disclosure of InterestNone Declared

BRUNNER SYNDROME: FROM GENETICS TO PSYCHIATRY - CASE REPORT

IntroductionMonoaminergic neurotransmitters affect motor control, emotions and cognitive functions. Their relative abundance depends on the action of monoamine oxidase A (MAOA) which catalyses their degradation into inactive metabolites. Brunner syndrome is a rare chromosome X-linked recessive inheritance genetic disorder, which causes loss of function of the MAOA gene, leading to a relative increase in monoamines in affected individuals (typically males). It manifests with moderate intellectual developmental disturbance associated with maladaptive externalising behaviours, low frustration tolerance and marked impulsivity.ObjectivesTo present a clinical case of patient diagnosed with Brunner Syndrome presenting with suicidal and homicidal ideation and to discuss it based on a non-systematic review of the literature.MethodsCase report and non-systematic review of the literature.Results: Case ReportMale born with neonatal asphyxia that consequently presented developmental retardation characterised by learning difficulties and emotional dysregulation. At 18 years of age, he began follow-up in Psychiatry due to self-injurious behaviours and several reactive suicide attempts (SA), being diagnosed with Intellectual Disability. At 22, he was hospitalised due to reactive depression, being discharged doing well with valproate, fluoxetine and olanzapine. Shortly after, he was arrested (aged 23-28) for attempted murder followed by SA. During imprisonment, he was diagnosed with Brunner’s Syndrome after his younger brother diagnosis. At 31, he was hospitalised for suicidal and homicidal ideation, revealing high impulsiveness and low frustration tolerance, and was discharged with compulsory psychiatric treatment. Three weeks later he was again hospitalised for symptoms recurrence having improved on Sertraline 50mg and Aripiprazole 400mg monthly.DiscussionAlthough scarce, the available evidence suggests that dietary modifications and the use of selective serotonin reuptake inhibitors may improve behaviour, reduce serotoninergic symptoms and possibly reverse some neurochemical abnormalities.ConclusionsBrunner syndrome is a rare genetic disorder with neuropsychiatric manifestations, whose course, treatment and prognosis are currently poorly known. Thus, the current treatment is empirical and further studies are needed.Disclosure of InterestNone Declared

Molecular Investigation of the Antitumor Effects of Monoamine Oxidase Inhibitors in Breast Cancer Cells.

The catalytic activity of monoamine oxidase A (MAO-A) has been linked to tumorigenesis due to the production of reactive oxygen species (ROS) and the resulting oxidative stress. MAO-A inhibition revealed a beneficial role in prostate and lung cancer treatment. This study is aimed at evaluating the effect of different monoamine oxidase A inhibitors (MAO-AIs) on the proliferation and progression of breast cancer cell lines. The cell viability assay was used to evaluate the antiproliferative and combined effects of MAO-AIs. Cell migration was evaluated using wound healing, invasion, and colony formation assays. The underlying mechanism of cell death was studied using flow cytometry. The real-time polymerase chain reaction was used to determine the relative gene expression. Finally, MAO-A activity in breast cancer cells was evaluated using an MAO-A activity assay. According to the results, the examined MAO-AIs significantly inhibited the proliferation of breast cancer cells in a dose-dependent manner. In breast cancer cells, the combination of anticancer drugs (doxorubicin or raloxifene) with MAO-AIs resulted in a synergistic effect. MAO-AIs significantly reduced wound closure and invasion ability in breast cancer cells. Also, MAO-AIs reduced the colony count and size of breast cancer cells. MAO-AIs resulted in significant proapoptotic activity in breast cancer cells. Finally, the MAO-AIs suppressed MAO-A, Bcl-2, and VEGF gene expressions in breast cancer cells relative to untreated cells. This study provides solid evidence supporting the anticancer effect of MAO-A inhibitors in breast cancer cells.

MAOA-uVNTR variations in schizophrenia: case and control study

BackgroundSchizophrenia, a chronic mental disorder, has been recognized as one of the heritable diseases with an increased level of dopamine neurotransmitter. Monoamine oxidase A (MAOA) plays a vital role in the catabolism of dopamine. It is a mitochondrial enzyme which is encoded by the MAOA gene located on the X chromosome. The aim of this study was to detect potential biomarker in order to diagnose schizophrenia. Hence, the association of uVNTR repetitions of the MAOA gene and Schizophrenia was investigated.MethodBlood samples were collected from 102 schizophrenic patients (67 males and 35 females), and 103 volunteers with mental health (65 males and 38 females). Genomic DNA was extracted and the uVNTR polymorphisms were examined using specific primed PCR.ResultsThe analysis indicated that genotype 3/3repetition (rep) showed the highest frequency in females. While genotype 4 and 3.5 reps revealed the highest frequencies among schizophrenic patients and healthy controls in men, respectively. There were no significant statistical differences in the number of uVNTR repeats of the MAOA gene between control and case individuals neither in women (OR = 0.35, 95% CI = 0.60–1.43 P = 0.845) nor in men (OR = 0.36, 95% CI = 0.80–1.64, P = 0.365).ConclusionIn the current study, the number of uVNTR sequence repetitions located in the promoter of the MAOA gene was not associated with the risk of schizophrenia in Iranian patients.

Regulation of the kynurenine/serotonin pathway by berberine and the underlying effect in the hippocampus of the chronic unpredictable mild stress mice

BackgroundDepression is a common mental disorder and is one of the main causes of disability. Berberine (BBR), the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects. This study was to investigate the hypothesis that BBR treats depressive-like behavior by shifting the balance of the kynurenine (KYN)/serotonin (5-HT) pathway toward the 5-HT pathway through downregulated indoleamine 2,3-dioxygenase 1 (IDO1), monoamine oxidase A (MAOA) and upregulated dopamine decarboxylase (DDC) in hippocampus. MethodA chronic unpredictable mild stress (CUMS) mice model of depression was established via 21 days unpredictable stimulation. Then the mice were randomly assigned into six groups, namely control, model, fluoxetine [FLU, (10 mg/kg)], BBRL (25 mg/kg), BBRM (50 mg/kg), and BBRH (100 mg/kg) groups. Behavioral assessments were conducted to evaluate the antidepressant effects of BBR. The levels of 5-HT, KYN, tryptophan (TRP), and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were estimated using high performance liquid chromatography (HPLC). The mRNA and protein levels of DDC, MAOA and IDO1 in hippocampus were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot (WB), respectively. ResultThe results showed that a successful CUMS mice model was established through 21 days of continuous unpredictable stimulation, as indicated by the significant decrease in locomotor activity and increase in immobility time, reduction in body weight and sucrose preference rate etc. Compared with the normal group, the concentrations of KYN/TRP had significantly increased (p## <0.01) and 5-HT/5-HIAA had decreased (p#<0.05) at day 21 in the control group, but then improved after drug treatment with FLU and BBR. Compared with the normal group, the mRNA of IDO1 and MAOA were significantly upregulated (p#<0.05) in the control group, MAOA and IDO1 gene were downregulated by FLU and BBR treatment. Protein expressions of IDO1 and MAOA was significantly increased (p#<0.05) and DDC downregulated (p##<0.01). BBR treatment downregulated IDO1 and MAOA, upregulated DDC. ConclusionsBBR reversed the abnormalities of the KYN/5-HT pathway in depressed mice and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in mice hippocampus tissue.

IDENTIFICATION OF MONOAMINOXIDASE-A GENE PROMOTER POLYMORPHISM (MAOA-UVNTR) AND THEIR RELATIONSHIP WITH AGGRESSIVE BEHAVIOR IN UKRAINIAN CHILDREN.

to investigate the interactive effect of monoamine oxidase-A gene promoter polymorphism (MAOA-uVNTR) and environmental factors on the development of aggressive behavior. Genotyping of the MAOA-uVNTR polymorphism was performed in 144 boys and girls aged from 10 to 16 years, genotypes were grouped by a high and low transcriptional activity. For the general assessment of the psycho-emotional sphere of children, the projective method «non-existent animal» was used, the indicators and forms of aggression were determined according to the method of A. Bass and A. Darky. It was found the predominant allelic variants of the MAOA gene with 3 (S) and 4 (L) tandem repeats. The presence of close relationships between the dependent variable «aggressive behavior» and the predictor variables: «family disadvantage index» and «MAOA-uVNTR genotype» was established. It has been proven that the presence of the highly active allele (L) in the genotype reduces the chances of developing general aggression, delinquent behavior, physical aggression, open aggression, negativism, and externalization. The MAOA genotype of the high-activity allele (L) moderated the impact of stressful life events, and the low-activity allele S was associated with increased aggression in girls and boys who experienced severe stress.

Relationship between the monoamine oxidase gene overactivity and the other pathophysiological and behavioral parameters implicated in memory deficiency in albino Winstar rats as Alzheimer’s disease model

The current study aimed to assess the pathophysiology mechanisms that mediate the effect on albin winstar rats' memory induced by the co -administration of fluoride and aluminum sulfate, as a model of Alzheimer's disease. This was done by assessing monoamine oxidase-A (MAO-A) activity, antioxidant activity, H2O2 and amyloid-β concentration in the hippocampus, embedded deep into the brain's temporal lobe, and level of cytokines in serum. The polymerase chain reaction approach was used to genotyping MAO-A, followed by single -stranded conformational polymorphism (SSCP) coupled with sequencing technique. The experimental animals were divided into two groups: control and treated groups. The uptake of heavy metals led to significantly increased MAO-A activity, amyloid -β deposition, H2O2 and cytokines levels in the treated group. However, the finding showed a significant decrease in antioxidant activity in the treated group. The results indicated that metals caused memory and learning impairments. PCR -SSCP genotyping showed many SNPs and haplotypes of the MAO-A exon 2 region, which showed the MAO-A gene polymorphism changes associated with Alzheimer's disease. The overall results indicated a role of metals to induce oxidative stress stimulating pathophysiological hallmarks in the hippocampus due to an increase in the influx of monoamine oxidase expression, which has been implicated in impaired memory, this study focused on the genetic variation of the exon 2 in monoamine oxidase-A gene and its relationship to Alzheimer's disease with the presence of several single nucleotide polymorphisms that may be related to Alzheimer's disease model in rats.

Brunner syndrome associated MAOA mutations result in NMDAR hyperfunction and increased network activity in human dopaminergic neurons

Monoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Among these, Monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene have been associated with Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function, specifically in dopaminergic (DA) neurons. Here we generated human induced pluripotent stem cell (hiPSC)-derived DA neurons from three individuals with Brunner syndrome carrying different mutations and characterized neuronal properties at the single cell and neuronal network level in vitro. DA neurons of Brunner syndrome patients showed reduced synaptic density but exhibited hyperactive network activity. Intrinsic functional properties and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected in DA neurons of individuals with Brunner syndrome. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), resulting in increased NMDAR-mediated currents. By correcting a MAOA missense mutation with CRISPR/Cas9 genome editing we normalized GRIN2A and GRIN2B expression, NMDAR function and neuronal population activity to control levels. Our data suggest that MAOA mutations in Brunner syndrome increase the activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to the etiology of Brunner syndrome associated phenotypes.

Roles of Hostility and Depression in the Association between the MAOA Gene Polymorphism and Internet Gaming Disorder.

The metabolism of bioamine in the central nervous system contributes to the development of addiction. We examined the roles of hostility and depression in the association between internet gaming disorder (IGD) and monoamine oxidase-A (MAOA) EcoRV polymorphism (rs1137070). A total of 69 adults with IGD and 138 without IGD were recruited through diagnostic interviewing. We evaluated participants for rs1137070, depression, and hostility. The participants with the TT genotype of rs1137070 had a higher odds ratio of 2.52 (1.37–4.64) for IGD compared with the C carriers. Expressive hostility behavior and hostility cognition mediated the association between rs1137070 and IGD. Indicating lower MAOA activity, the TT genotype predicted IGD and higher expressive hostility behavior and hostility cognition. Expressive hostility behavior and hostility cognition may underline the association between rs1137070 and IGD. Assessment of and intervention for hostility behavior and cognition should be provided to attenuate the risk of IGD, particularly in those with the TT genotype. Further brain imaging or neurobiological studies are required to elucidate the possible mechanism underlying the association between MAOA activity and IGD.

Bidirectional Cross-talk between MAOA and AR Promotes Hormone-Dependent and Castration-Resistant Prostate Cancer.

Androgen receptor (AR) is the primary oncogenic driver of prostate cancer, including aggressive castration-resistant prostate cancer (CRPC). The molecular mechanisms controlling AR activation in general and AR reactivation in CRPC remain elusive. Here we report that monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines, reciprocally interacts with AR in prostate cancer. MAOA was induced by androgens through direct AR binding to a novel intronic androgen response element of the MAOA gene, which in turn promoted AR transcriptional activity via upregulation of Shh/Gli-YAP1 signaling to enhance nuclear YAP1-AR interactions. Silencing MAOA suppressed AR-mediated prostate cancer development and growth, including CRPC, in mice. MAOA expression was elevated and positively associated with AR and YAP1 in human CRPC. Finally, genetic or pharmacologic targeting of MAOA enhanced the growth-inhibition efficacy of enzalutamide, darolutamide, and apalutamide in both androgen-dependent and CRPC cells. Collectively, these findings identify and characterize an MAOA-AR reciprocal regulatory circuit with coamplified effects in prostate cancer. Moreover, they suggest that cotargeting this complex may be a viable therapeutic strategy to treat prostate cancer and CRPC. SIGNIFICANCE: MAOA and AR comprise a positive feedback loop in androgen-dependent and CRPC, providing a mechanistic rationale for combining MAOA inhibition with AR-targeted therapies for prostate cancer treatment.

The Effects of Age and Sex on the Interaction Between Monoamine Oxidase A VNTR and Psychopathic Traits in Children and Adolescents

Psychopathy-related behaviors increase the risk of youth violence and death. The mixed results in the literature regarding the association between Monoamine Oxidase A (MAOA)-VNTR and psychopathy in children demonstrate that both sex and age can influence the contribution of the MAOA gene. This study examines the developmental trajectory of the association between sex, MAOA-VNTR, and psychopathic traits in a unique sample of clinically aggressive children.

The Effects of Childhood Maltreatment on Non-Suicidal Self-Injury in Male Adolescents: The Moderating Roles of the Monoamine Oxidase A (MAOA) Gene and the Catechol-O-Methyltransferase (COMT) Gene

(1) Background: Numerous studies suggest strong associations between childhood maltreatment and nonsuicidal self-injury (NSSI); this is also true for the roles of dopaminergic genes in the etiology of some psychopathologies related to NSSI. Investigating the interactions of environments and genes is important in order to better understand the etiology of NSSI. (2) Methods: Within a sample of 269 Chinese male adolescents (Mage = 14.72, SD = 0.92), childhood maltreatment and NSSI were evaluated, and saliva samples were collected for MAOA T941G and COMT Val158Met polymorphism analyses. (3) Results: The results revealed no primary effects attributable to MAOA T941G and COMT Val158Met polymorphism on NSSI. However, there was a significant three-way interaction between MAOA, COMT, and child abuse (β = −0.34, p < 0.01) in adolescent NSSI. Except for carriers of the T allele of MAOA and the Met allele of COMT, all studied male adolescents displayed higher NSSI scores when exposed to a higher level of child abuse. A similar three-way interaction was not observed in the case of child neglect. (4) Conclusions: The results indicate that the MAOA gene and COMT gene play moderating roles in the association between child abuse and NSSI of male adolescents and suggest the polygenic underpinnings of NSSI.

Association of variable number of tandem repeats (VNTR) and T941G polymorphism of monoamine oxidase (MAO-A) gene with aggression in Pakistani subjects.

Human behavioral traits are known to be significantly heritable. Certain individuals have a greater tendency of negative behavioral aspects including aggression. The quest to identify tunderlying genetic causes has led to identification of a number of genetic markers, one of them is the monoamine oxidase-A (MAO-A) gene. We aimed to genotype a variable number of tandem repeats (VNTRs) in the promoter region and a functional SNP within this gene (T941G, dbSNP ID: rs6323) in the recruited cohort of 482 subjects. After DNA isolation, genotyping was done by PCR-RFLP and the results were confirmed by sequencing. For VNTRs, the results showed, highest frequency of 3.5 repeats in males and 4 repeats in females in the promoter region. The genotype frequencies for the SNP in cases were GG=16.3%, TG=20.6% and TT=63.1%, while in controls, the frequencies were GG=12.7%, TG=6.3%, and TT=81.0%. The allele frequencies were significantly different between cases and controls (p=0.015; OR=1.51; CI=1.085-2.102). The selected VNTR and SNP appeared to be significantly associated with aggression. These VNTRs and SNP have not been studied previously in the Pakistani population, hence they represent a unique ethnic group. These results, however, would have to be replicated in larger cohorts.