Monoamine Oxidase A Polymorphisms Research Articles

Unraveling the Contribution of Serotonergic Polymorphisms, Prefrontal Alpha Asymmetry, and Individual Alpha Peak Frequency to the Emotion-Related Impulsivity Endophenotype

The unique contribution of the serotonin transporter-linked polymorphic region (5-HTTLPR), intronic region 2 (STin2), and monoamine oxidase A (MAO-A) genes to individual differences in personality traits has been widely explored, and research has shown that certain forms of these polymorphisms relate to impulsivity and impulsivity-related disorders. Humans showing these traits are also described as having an asymmetrical prefrontal cortical activity when compared to others. In this explorative study, we examine the relationship between serotonergic neurotransmission polymorphisms, cortical activity features (prefrontal alpha asymmetry, individual alpha peak frequency [iAPF]), emotion-related and non-emotion-related impulsivity in humans. 5-HTTLPR, MAO-A, and STin2 polymorphisms were assessed in blood taken from 91 participants with high emotion-related impulsivity levels. Sixty-seven participants completed resting electroencephalography and a more comprehensive impulsivity index. In univariate analyses, iAPF correlated with both forms of emotion-related impulsivity. In multiple linear regression models, 5-HTTLPR polymorphism (model 1, adj. R2 = 15.2%) and iAPF were significant interacting predictors of emotion-related impulsivity, explaining a large share of the results’ variance (model 2, adj. R2 = 21.2%). Carriers of the low transcriptional activity 5-HTTPLR and MAO-A phenotypes obtained higher emotion-related impulsivity scores than others did. No significant results were detected for non-emotion-related impulsivity or for a form of emotion-related impulsivity involving cognitive/motivational reactivity to emotion. Our findings support an endophenotypic approach to impulsivity, showing that tri-allelic 5-HTTLPR polymorphism, iAPF, and their interaction are relevant predictors of one form of emotion-related impulsivity.

Effects of Childhood Adversity and Its Interaction with the MAOA, BDNF, and COMT Polymorphisms on Subclinical Attention Deficit/Hyperactivity Symptoms in Generally Healthy Youth.

We aimed to investigate the effects of childhood adversity and its interaction with the polymorphisms in the monoamine oxidase A (MAOA), brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) genes on attention and hyperactivity disorder (ADHD) symptoms in a community sample of generally healthy youth. Participants (N = 432) completed questionnaires assessing ADHD symptoms (i.e., inattention, hyperactivity, and impulsiveness) and adverse childhood experiences, such as adverse environments (AEs) and childhood maltreatment (CM). Salivary genomic DNA was used to test polymorphisms in MAOA, BDNF, and COMT genes. A gene score (GS) was created based on the number of risk allele in the studied genes. Multiple linear regressions were used to examine the genetic and environmental effects on ADHD symptoms. The univariate analysis indicated that CM was significantly associated with inattention (β = 0.48 [95% confidence interval 0.16–0.79]), hyperactivity (0.25 [0.06–0.45]), and impulsiveness (1.16 [0.26–2.05]), while the GS was associated with hyperactivity (0.22 [0.11–0.33]) and impulsiveness (0.56 [0.06–1.05]). Only the GS remained significantly associated with hyperactivity (0.25 [0.12–0.37]) and impulsiveness (0.79 [0.20–1.38]) when the gene-environment interaction term was added in the model. No effects were found for AE and the gene-environment interaction term. In conclusion, CM was associated with ADHD symptoms in emerging adulthood. Genetic factors may also play a significant role in the association with these outcomes.

Examination of associations between personality traits, and polymorphisms of MAO-A and 5-HTT with the severity of menopausal symptoms and depression levels.

The aim of the present study was to investigate the association between different personality traits with monoamine oxidase A (MAO-A) and serotonin transporter (5-HTT), and to examine their effects on the severity of menopause symptoms as well as the levels of depression in menopausal women. The study was designed as an analytical cross-sectional study, performed on 132 healthy post-menopausal women in Iran. Personality was assessed using the Revised Edition of the NEO Personality Index (Neuroticism-Extroversion-Openness-Five Factor Inventory). The symptoms score sheet, used for measuring menopausal symptoms, was used to classify the participants according to their menopausal symptoms. Furthermore, Beck Depression Inventory short version was also used to assess depressive symptoms. Examination of blood samples taken from all participants was to identify DNA polymorphisms of 5-HTT using PCR. The results of the present study showed that a high level of neuroticism (P<0.0001), low levels of extroversion (P<0.002), an openness to experience (P=0.039) and conscientiousness (P=0.001) were all positively associated with the severity of menopausal symptoms. In addition, a high level of neuroticism (P<0.0001), low levels of extroversion (P<0.0001), and a low level of agreeableness (P<0.024) and conscientiousness (P<0.0001) were all positively associated with depressive symptoms. There was no statistically significant association between MAO-A and 5-HTT polymorphisms with menopause and depression scores. Based on these results, there appears to be a significant association between personality traits with both depression and menopausal symptoms. Identification of homogeneous groups of women who are predisposed to depression and severe menopausal symptoms may allow for the implementation of early prevention programs.

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD. The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire. There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype. The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.

Exogenous testosterone and the monoamine-oxidase A polymorphism influence anger, aggression and neural responses to provocation in males

Testosterone and the monoamine oxidase-A (MAOA) polymorphism are potential neuromodulators for aggression. By acting on similar brain circuits, they might interactively influence human behavior. The current study investigates the causal role of testosterone on aggression-related brain activity and the potential interaction with the MAOA polymorphism. In a double-blind process, 93 healthy males received a testosterone or placebo gel. In an fMRI session, participants performed a Taylor aggression paradigm in which they received provoking feedback and could afterwards decide how aggressively they would react. Testosterone and cortisol levels as well as subjective anger were assessed prior and after the task. Circulating testosterone levels were higher in carriers of the long compared to the short MAOA allele. An interaction of the MAOA polymorphism and testosterone administration was identified in the cuneus, where short allele carriers in the placebo group showed diminished activity in the decision period. Task-related anger was significantly higher in this group. Overall, a mesocorticolimbic network was implicated in processing of high versus low provoking feedback, and core hubs of the default mode network were implicated in the subsequent decision after high versus low provocation. Testosterone administration increased activation in this network. The data provides evidence for an interaction of the MAOA polymorphism and exogenous testosterone on anger and suggests that interactive effects on the brain signal could underlie differential emotional reactivity. The increased default mode activation in the testosterone group suggests an enhanced engagement of social cognition related regions possibly supporting responsivity towards social provocation.This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms. We studied 18 ASPD males with a history of violent offending and 20 healthy male controls. Genomic DNA was extracted from peripheral leukocytes to determine MAO-A genetic polymorphisms. Subjects underwent a T1-weighted MRI anatomical brain scan that provided vertex-wise measures of amygdala shape and surface area and OFC cortical thickness. We found that ASPD + PP subjects with MAOA-L exhibited decreased surface area in the right basolateral amygdala nucleus and increased surface area in the right anterior cortical amygdaloid nucleus versus healthy MAOA-L carriers. This study is the first to describe genotype-related morphological differences of the amygdala in a population marked by high aggression. Deficits in emotional regulation that contribute to the violence of ASPD + PP may relate to morphological changes of the amygdala under genetic control.

Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Juvenile male rhesus macaques received therapeutic doses of fluoxetine daily from one to three years of age and were compared to vehicle-treated controls (N=16/group). Genotyping for monoamine oxidase A (MAOA) polymorphisms was used to form subgroups (N=8) with high and low expression of the gene. Behavioral responses were scored during 30-second exposures to pictures differing in affective content. As expected from its therapeutic effect, fluoxetine decreased the behavioral response to emotionally evocative pictures. A 44% reduction in number of expressive behaviors was seen, but only in subjects with low expression MAOA polymorphisms. In general, this effect occurred for pictures of varying affective content and was not due to altered occurrence of one specific behavior or type of behavior. The drug*genotype interaction was seen after one and two years of treatment and did not reverse one year after discontinuation of dosing. Two potential translational implications are suggested: (1) MAOA genetic polymorphisms may be the source of some of the variability in response to fluoxetine treatment in children; (2) extended fluoxetine treatment during juvenile brain development may result in persistent effects on emotional regulation.

Effects of MAOA genotype and childhood experiences of physical and emotional abuse on aggressive behavior in adulthood

A functional polymorphism in the monoamine oxidase A (MAOA) gene located on the X chromosome (Xp11.23-11.4) has earned the nickname “warrior gene” because of its association with antisocial behavior and delinquency. Previous findings on adults and adolescents have found some evidence that the MAOA gene moderates the impact of childhood abuse experiences on the risk of developing aggressive behavior. Thus far, however, attempts to replicate these findings have been mixed. The aims of the present study were to investigate whether the MAOA polymorphism affects aggressive behavior alone and in combination with childhood abuse experiences. We tried to replicate this using a sample of 1447 male and 2179 female Finnish twins and their siblings. In the present study, the Childhood Trauma Questionnaire and Aggression Questionnaire were used. There was a positive correlation between childhood abuse experiences and later aggressive behavior in adolescence or adulthood both for men and women. The results showed the effects of the 4-repeat allele of MAOA promoter polymorphism on physical aggressive behavior for women. It seems that there is an interaction between the 3-repeat allele of MAOA promoter polymorphism and emotional abuse experiences on aggressive behavior for women. In conclusions, this study, using a large population-based sample, found partial support for an interaction between MAOA genotype and childhood abuse experiences on aggressive behavior.

COMT and MAO-A polymorphisms and obsessive-compulsive disorder: a family-based association study.

ObjectiveObsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.MethodsTransmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.ResultsOCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.ConclusionsThe findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.

Fetal Iron Deficiency and Genotype Influence Emotionality in Infant Rhesus Monkeys1–3

Background: Anemia during the third trimester of fetal development affects one-third of the pregnancies in the United States and has been associated with postnatal behavioral outcomes. This study examines how fetal iron deficiency (ID) interacts with the fetal monoamine oxidase A (MAOA) genotype. MAOA metabolizes monoamine neurotransmitters. MAOA polymorphisms in humans affect temperament and modify the influence of early adverse environments on later behavior.Objective: The aim of the study was to advance translation of developmental ID research in animal models by taking into account genetic factors that influence outcomes in human populations.Methods: Male infant rhesus monkeys 3–4 mo old born to mothers fed an ID (10 ppm iron) diet were compared with controls (100 ppm iron). Infant monkeys with high- or low-transcription rate MAOA polymorphisms were equally distributed between diet groups. Behavioral responses to a series of structured experiences were recorded during a 25-h separation of the infants from their mothers.Results: Infant monkeys with low-transcription MAOA polymorphisms more clearly demonstrated the following ID effects suggested in earlier studies: a 4% smaller head circumference, a 39% lower cortisol response to social separation, a 129% longer engagement with novel visual stimuli, and 33% lesser withdrawal in response to a human intruder. The high MAOA genotype ID monkeys demonstrated other ID effects: less withdrawal and emotionality after social separation and lower “fearful” ratings.Conclusion: MAOA × ID interactions support the role of monoamine neurotransmitters in prenatal ID effects in rhesus monkeys and the potential involvement of common human polymorphisms in determining the pattern of neurobehavioral effects produced by inadequate prenatal nutrition.

The assessment of the relationship between personality, the presence of the 5HTT and MAO-A polymorphisms, and the severity of climacteric and depressive symptoms in postmenopausal women.

The purpose of this study is to determine the relationship between personality, the serotonin transporter (5HTT) and monoamine oxidase A (MAO-A) polymorphisms and the severity of climacteric and depressive symptoms in postmenopausal women. The study involved 272 healthy postmenopausal women from Poland. This survey-based study was performed using the following: the Beck Depression Inventory for depressive symptoms, the Blatt–Kupperman Menopausal Index and the Neuroticism-Extroversion-Openness-Five Factor Inventory for personality. A polymerase chain reaction was employed to identify the DNA polymorphisms. The women were aged 55.4 ± 5.5 years on average. Significant correlations were proved between the allele frequency of the 30-bp variable-number tandem repeat (VNTR) polymorphism in the MAO-A promoter region and the incidence of depressive symptoms in the women analysed (p ≤ 0.05), as well as between the severity of climacteric symptoms in the postmenopausal women and the allele frequency of the polymorphism in the 5HTT gene (the 5HTT ‘s’ variant) (p ≤ 0.05). There was a significant correlation between the severity of climacteric and depressive symptoms (p < 0.001). (1) The severity of climacteric and depressive symptoms depends on personality traits. (2) Personality traits are biologically determined, and the level of their expression is associated with the 5HTT polymorphism. (3) Identification of homogeneous groups of women having predispositions to depressive and severe climacteric symptoms may help to implement early prevention programmes for this group of recipients.

Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms: combined risk for later cognitive performance in rhesus monkeys

Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated withindividual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10ppm, ID) or an iron-sufficient (100ppm, IS) diet during gestation (n=10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.

Neuropsychological Correlates of Transcription Factor AP-2Beta, and Its Interaction with COMT and MAOA in Healthy Females

Background: The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. Methods: This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). Results: The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). Conclusion: The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability.

The 5HTT and MAO-A polymorphisms associate with depressive mood and climacteric symptoms in postmenopausal women

The aim of this study was to assess the influence of the 44-bp polymorphism in the 5HTTLPR (SLC 6A4) (serotonin-transporter-linked polymorphic region, solute carrier family 6 member 4) promoter region and the 30-bpVNTR (variable number of tandem repeats) polymorphism in the MAO-A (monoamine oxidase A) promoter region on the prevalence of depressive mood and the severity of climacteric symptoms in postmenopausal women. The study involved 630 women from northern Poland who had their last menstrual period at least one year before the study. The women did not abuse alcohol or cigarettes, had not been diagnosed as having endocrinological, cancerous or mental diseases, and had not received psychiatric treatment by the time. This survey-based study was performed using the following research instruments: the Beck Depression Inventory (BDI), to evaluate depressive symptoms, and the Blatt-Kupperman Menopausal Index, to measure the severity of climacteric symptoms. The average age of the women was 57.5 ± 6.4 years. Depressive symptoms of different severity according to the BDI were diagnosed in 29.2% of the women (minor-18.6%, moderate-7.1%, severe-3.5%) and according to the Blatt-Kupperman Menopausal Index were diagnosed in 42% of the women (minor-24.1%, moderate-9.2%, severe-8.7%). Allele 'l' was significantly more common in the women without climacteric symptoms than those with minor, moderate or severe climacteric complaints (p ≤ 0.05). There was a significant correlation between the severity of climacteric and depressive symptoms (p ≤ 0.05). The women who had severe climacteric symptoms also had more severe depressive symptoms. 1. The 5HTTLPR gene polymorphism contributes to climacteric symptoms in postmenopausal women. 2. The Blatt-Kupperman Menopausal Index is an instrument which can not only be used for the measurement of the severity of climacteric symptoms but also the early detection of perimenopausal women at the risk of developing depressive symptoms.

Monoamine Oxidase A Gene Polymorphism and the Pathogenesis of Sudden Infant Death Syndrome

To test the hypothesis that there is a significant association between functionally relevant allelic variants of the monoamine oxidase A (MAO-A) polymorphism and sudden infant death syndrome (SIDS). In a case-control study of 142 cases of SIDS and 280 sex-matched control cases, the distribution of allelic and genotype variants of a promoter polymorphism of the MAO-A gene was examined using polymerase chain reaction locus amplification and fluorescence based fragment length analysis. There was a significantly differential distribution of allelic and genotype variants between females with SIDS and controls. Moreover, there was a significant association between SIDS in females and allelic and genotype variants, each related to a higher transcriptional activity at the MAO-A locus. Our results suggest a role of MAO-A in female SIDS pathogenesis exerted by functionally relevant allelic and genotype variants of the MAO-A polymorphism. However, with the complex and inconsistent evidence available to date, the impact of the MAO-A promoter polymorphism on SIDS etiology remains unclear.

Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4 %. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30 bp-promoter VNTR and DAT1 40 bp 3' UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95 % confidence interval (95 % CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P < 0.01, OR = 3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P < 0.01, OR = 2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P < 0.01, OR = 4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia.

Different Impacts of Aquaporin 4 and MAOA Allele Variation Among Olanzapine, Risperidone, and Paliperidone in Schizophrenia

Apoptosis has been considered to be involved in schizophrenia. Water channels are modulated just before apoptosis. In the aquaporin family, aquaporin 4 (AQP-4) is most highly expressed in the brain and is supposed to play an important role in a neuronal environment. In this clinical study, we investigated the relationship between the AQP-4 polymorphism and drug response in schizophrenia under the control of the MAOA (monoamine oxidase A) promoter gene. We recruited 91 patients with schizophrenia, and they were randomized to receive olanzapine (n = 44), risperidone (n = 23), or paliperidone (n = 24). Genotyping of AQP-4 and MAOA polymorphisms was done in all patients. Patients with the AQP-4 non-C polymorphism needed a higher dosage of olanzapine for treatment (z = 4.163, P = 0.041), and patients with a short form of the MAOA polymorphism needed a higher dosage of risperidone for treatment (z = 5.124, P = 0.024). Patients who smoked cigarettes needed a higher dosage of olanzapine for treatment (z = 4.905, P = 0.027), but cigarette smoking did not affect the dosage of paliperidone. The AQP-4 polymorphism may have an effect in influencing the dosage of olanzapine. However, the roles of AQP-4 polymorphisms in the blood-brain barrier and different neuroprotective effects need further exploration in future studies.

MAOA, MTHFR, and TNF-β genes polymorphisms and personality traits in the pathogenesis of migraine

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

Association of MAOA and COMT gene polymorphisms with palatable food intake in children

Several studies have implicated dopamine (DA) in appetite regulation. The enzymes catechol-o-methyltransferase (COMT) and monoamine oxidase A (MAOA) control DA availability and their genes have well-characterized functional variants. In this study, we examined three polymorphisms in these genes, T941G and MAOAu-VNTR in the MAOA gene and Val158Met in the COMT gene, to investigate how heritable variations in enzymes that determine DA levels might influence food intake and nutritional status. This investigation was a cross-sectional examination of 354 Brazilian children of three to four years old. Polymorphisms were analyzed by PCR-based methods. Means of dietary and anthropometric data were compared among genotypes by one-way analyses of variance or Kruskal Wallis tests. The MAOAu-VNTR and COMT Val158Met polymorphisms were associated with the amount of palatable food intake in boys. Presence of the MAOAu-VNTR⁎long allele was associated with higher intake of lipid-dense foods (LDF) when compared with the ⁎short allele (P=.009); the amount of sugar-dense foods (SDF) intake was also higher in males carriers of the MAOAu-VNTR⁎long allele than in carriers of the ⁎short allele (P=.034). In the girls' sample, MAOAu-VNTR polymorphism was not associated with food intake and nutritional status. Carriers of the COMT Val158Met⁎Val allele presented higher intake of LDF when compared with Met/Met homozygotes (P=.008). This study provides the first indication that genetic variants of enzymes that control DA availability might be involved in determination of the amount of palatable food intake in children.

Monoamine oxidase A variants are associated with heavy betel quid use

Few studies have investigated whether genetic abnormalities predispose individuals to heavy betel quid (BQ) use. One of the major ingredients of BQ, arecoline, is known to affect the expression of monoamine oxidase A (MAO-A). We investigated the extent to which arecoline inhibits MAO-A expression and the role of MAO-A polymorphisms in BQ use in Taiwanese aborigines. Cytotoxicity assays, microarrays and quantitative reverse transcriptase-polymerase chain reaction were used to examine the effects of arecoline and areca nut extract (ANE) on cell viability and MAO-A expression in neuroblastoma SH-SY5Y cells. After identifying the effective concentrations of arecoline and ANE in vitro, we examined the in vivo effects of these compounds using a rat model system. Our results indicate that arecoline and ANE inhibit MAO-A expression both in vitro and in vivo. In addition, we examined the correlation between plasma MAO-A activity and cumulative exposure to BQ in humans. We recruited 1307 aborigines from a large-scale community-based survey to determine whether MAO-A variants were associated with high BQ use and a preference for use with smoking or alcohol and whether gender bias existed. MAO-A expression was significantly downregulated by arecoline and ANE at 100-200 µg/ml and in rat whole brains on days 30 and 45. MAO-A activity levels in human plasma were positively correlated with the extent of BQ exposure, and individuals with at-risk alleles exhibited lower activity, although this result did not reach statistical significance. We found two single nucleotide polymorphism (SNPs) in aboriginal males [rs2283725, odds ratio (OR) = 2.04; rs5953210, OR = 2.03] and females (rs2283725, OR = 1.54; rs5953210, OR = 1.59) that were associated with heavy BQ use. Those individuals carrying at-risk alleles who drank alcohol were twice as likely to be heavy BQ users. However, the effects of these SNPs on BQ use were significant even after controlling for alcohol use. Our results suggest that two specific loci may confer a susceptibility to BQ abuse and affect MAO-A enzymatic activity.