Do Polymorphisms Predict Hypnotherapy Response in Children With Functional Abdominal Pain Disorders: An Explorative Study.

Genetic variations, in specific COMT , OPRM1 , and MAO-A polymorphisms, have been associated with hypnotizability in adults. The aim of this exploratory study was to investigate whether these polymorphisms are also associated with response to hypnotherapy (HT) in children. Patients (8-18 years, n = 260) diagnosed with a functional abdominal pain disorder (FAPD) from a previous trial assessing HT efficacy were approached for participation and 144 agreed to collect a buccal sample. Primary aim was to explore the association between COMT , OPRM1 , and MAO-A polymorphisms with treatment success (TS) after 3-month HT. Additionally, associations between these polymorphisms and adequate relief, anxiety, depression, quality of life, somatization, hypnotic susceptibility, expectations, pain beliefs, and coping strategies were evaluated. Participants with different variations of COMT , MAO-A , and OPRM1 achieved similar TS levels ( P > 0.05). No associations were found between these polymorphisms and secondary outcomes. This suggest that in pediatric patients with FAPDs, COMT , OPRM1 , and MAO-A polymorphisms do not predict HT response.

A study on methylation of two CpG islands of MAOA gene promoter among opium-addicted males undergoing methadone treatment.

The association between methylation of MAOA gene promoter and alcohol and nicotine dependence has been demonstrated in women but not in men yet. Antisocial personality disorder (ASPD) and substance use disorders (SUD) are two types of disorders that could highly be influenced by methylation-induced changes in MAOA function. The aim of the current study is to investigate the effect of opioid addiction on methylation of MAOA gene promoter in males. DNA was extracted from the whole blood of all samples (29 opium-addicted individuals undergoing methadone treatment and 28 healthy people) according to the extraction protocol, followed by treating these samples with bisulfite kits. The investigated region including two CpG islands in the promoter region of MAOA gene contained 35 CpG dinucleotides investigated through Sanger sequencing method. The frequency of methylation at two CpG islands of MAOA gene promoter regions was equal to zero among addicted individuals undergoing methadone treatment and healthy peoples. Then, comparing methylation levels among the study group is not applicable. In conclusion, there was no association between opium addiction and methylation of the MAOA promoter regions in opium-addicted male undergoing methadone treatment.

Yin Yang 1 (YY1)-induced long intergenic non-protein coding RNA 472 (LINC00472) aggravates sepsis-associated cardiac dysfunction via the micro-RNA-335-3p (miR-335-3p)/Monoamine oxidase A (MAOA) cascade.

As a leading complication of sepsis, sepsis-induced cardiac dysfunction (SICD) contributed to the high mortality of patients with sepsis. Long non-coding RNA (LncRNA) LINC00472 has been reported to be in sepsis-induced disease. Nonetheless, its biological function and underlying molecular in SICD remain largely unknown. In this study, in vivo and in vitro SICD models were established via LPS treatment. H&E staining was employed for the evaluation of myocardial injury. ELISA assay was performed to detect cardiac Troponin I (cTnI), creatine kinase-MB (CK-MB), interleukin (IL)-1ß, and tumor necrosis factor-α (TNF-α) levels. Cardiomyocyte viability and apoptosis were assessed via CCK-8 and flow cytometry assays. The transcriptional regulation of YY1 on LINC00472 was demonstrated via ChIP assay. Besides, the interaction between YY1 and LINC00472, as well as the association between miR-335-3p and LINC00472 or MAOA were verified via luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Herein, highly expressed LINC00472 was observed in both in vivo and in vitro SICD models. LINC00472 knockdown substantially attenuated LPS-induced inhibition on cardiomyocyte viability and reversed cardiomyocyte apoptosis and inflammatory response mediated by LPS treatment. YY1 induced LINC00472 upregulation, thereby promoting cardiomyocyte dysfunction induced by LPS. In addition, MAOA upregulation or miR-335-3p inhibition could partly reverse the suppressive effect on LPS-induced cardiomyocyte dysfunction mediated by LINC00472 knockdown. Based on our results, it seemed that YY1-activated LINC00472 might contribute to SICD progression via the miR-335-3p/MAOA pathway.

Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated. METHODS: We used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints. RESULTS: The stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus. CONCLUSIONS: This study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.

The clinical value and potential molecular mechanism of the downregulation of MAOA in hepatocellular carcinoma tissues.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. METHODS: In-house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co-expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. RESULTS: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co-expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. CONCLUSIONS: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co-expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients.

Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells.

Geranylgeranoic acid (GGA) originally was identified in some animals and has been developed as an agent for preventing second primary hepatoma. We previously have also identified GGA as an acyclic diterpenoid in some medicinal herbs. Recently, we reported that in human hepatoma-derived HuH-7 cells, GGA is metabolically labeled from 13C-mevalonate. Several cell-free experiments have demonstrated that GGA is synthesized through geranylgeranial by oxygen-dependent oxidation of geranylgeraniol (GGOH), but the exact biochemical events giving rise to GGA in hepatoma cells remain unclear. Monoamine oxidase B (MOAB) has been suggested to be involved in GGOH oxidation. Here, using two human hepatoma cell lines, we investigated whether MAOB contributes to GGA biosynthesis. Using either HuH-7 cell lysates or recombinant human MAOB, we found that: 1) the MAO inhibitor tranylcypromine dose-dependently downregulates endogenous GGA levels in HuH-7 cells; and 2) siRNA-mediated MAOB silencing reduces intracellular GGA levels in HuH-7 and Hep3B cells. Unexpectedly, however, CRISPR/Cas9-generated MAOB-KO human hepatoma Hep3B cells had GGA levels similar to those in MAOB-WT cells. A sensitivity of GGA levels to siRNA-mediated MAOB downregulation was recovered when the MAOB-KO cells were transfected with a MAOB-expression plasmid, suggesting that MAOB is the enzyme primarily responsible for GGOH oxidation and that some other latent metabolic pathways may maintain endogenous GGA levels in the MAOB-KO hepatoma cells. Along with the previous findings, these results provide critical insights into the biological roles of human MAOB and provide evidence that hepatic MAOB is involved in endogenous GGA biosynthesis via GGOH oxidation.

Eggplant (Solanum spp) supplemented fruits diet modulated the activities of ectonucleoside triphosphate diphosphohydrolase (ENTPdase), monoamine oxidase (MAO), and cholinesterases (AChE/BChE) in the brain of diabetic Wistar male rats.

Type 2 diabetes mellitus is associated with complications such as Alzheimer disease (AD). Tropical eggplant (Solanum gilo, Solanum kumba, and Solanum aethiopicum) fruits have been extensively used for the treatment of different ailments. This study assesses the effect of an eggplant supplemented-diet on purinergic, monoaminergic, and cholinergic enzyme systems in diabetic male rats, besides determining the presence of alkaloids using GC-MS chromatography. Results from this study show that eggplant fruit diet modulates the activities of the enzymes in purinergic, monoaminergic, and cholinergic enzyme systems associated with AD-like symptoms. Solanum kumba-supplemented diet significantly (p < 0.05) reduced enzyme activities better than S. gilo and S. aethiopicum, which could be due to its rich phytochemical constituents. In conclusion, eggplant fruits could serve as a holistic measure in the prevention of diabetes-related complications such as neurodegenerative disease. PRACTICAL APPLICATIONS: The therapeutic management of diabetes fails to holistically address inflammatory response which likely contributes to type 2 diabetes mellitus (T2DM) occurrence by causing insulin resistance; this, in turn, is intensified in the presence of hyperglycemia to promote long-term complications such as neurodegenerative disorders. The health benefit of a tropical eggplant fruit diet inform a nutritional and therapeutic approach for the prevention and treatment of T2DM and its associated complications such as neurodegenerative disorders has been proved. The eggplant fruit-supplemented diet, which is cost-effective with little or no side effect, could substantially increase the antioxidant status and also modulate the activities of neuronal enzymes in a diabetic model with dementia, as well as Alzheimer's-like symptoms. This study, therefore, revealed more of the benefits of tropical eggplant fruits vis-à-vis their management in hyperglycemia-mediated neurodegeneration.

Brain region specific methylation and Sirt1 binding changes in MAOA promoter is associated with sexual dimorphism in early life stress induced aggressive behavior.

The maladaptive form of aggressive behavior confers risk for violence and criminal incidences with profound impact on society. Although considerable research has been devoted to elucidate the etiology of aggression, molecular correlates of sex differences remains largely unexplored. Also, little attention has been given to whether males and females respond differently to similar causal factor of aggression. Here, we show the possible association of brain region specific neural activity (c-Fos expression) and monoamine oxidase A (MAOA) epigenetic state with sexual dimorphism in peripubertal stress (PPS) induced adulthood aggression. While PPS adult males exhibited escalated aggression, females spent maximal time in social exploration. c-Fos expression was brain region and sex specific. In the PPS adult cohort, only males showed elevated c-Fos expression in the prefrontal cortex, indicative of their hyper-responsive behavior. MAOA expression and enzyme activity was reduced in hypothalamus and increased in prefrontal cortex of hyper-aggressive male mice. Investigation into the underlying mechanisms revealed hypomethylation in prefrontal cortex and hypermethylation in hypothalamus of MAOA promoter negatively correlating with the expression pattern. On the other hand, binding of Sirt1 to MAOA promoter was diametrically opposite being increased in prefrontal cortex and reduced in hypothalamus. In females, neither expression nor epigenetic state of MAOA gene was significantly altered between control and PPS adult mice. Our study revealed novel epigenetic correlates of sexual dimorphism in stress induced aggressive psychopathology. However, given the multi-factorial nature with environmental influences, further studies are warranted to uncover the biological hub.

Dereplication of Components Coupled with HPLC-qTOF-MS in the Active Fraction of Humulus japonicus and It's Protective Effects against Parkinson's Disease Mouse Model.

Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson's disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson's disease mouse model.

Post-Weaning Social Isolation Disturbs Gene Expression in Rat Brain Structures.

Post-weaning social isolation of male Wistar rats for 10 weeks led to an increase of their aggressiveness, sensorimotor reactivity, and cognitive deficiency, manifesting in training disorders evaluated by the acoustic startle response (amplitude of the response decreasing). Expression of gene encoding serine protease prolyl endopeptidase (EC 3.4.21.26) in the frontal cortex was higher than in control rats kept in groups, while the level of mRNA of the gene encoding dipeptidyl peptidase IV (EC 3.4.14.5) did not differ from the control in any of the brain structures. The levels of serotonin transporter gene mRNA in the striatum and hypothalamus were higher than in the control. No appreciable changes in the expression of genes encoding tryptophan hydroxylase-2 and monoaminoxidase A and B in the frontal cortex, striatum, amygdala, hypothalamus, and hippocampus were detected. The data indicated the involvement of genes associated with the serotoninergic system in the mechanisms of mental disorders induced by post-weaning social isolation and suggest the gene encoding prolyl endopeptidase as a candidate gene involved in the pathogenesis of these disorders.

Moringa oleifera extract attenuates the CoCl2 induced hypoxia of rat's brain: Expression pattern of HIF-1α, NF-kB, MAO and EPO.

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat's brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat's brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.

Silver nanoparticle exposure in pregnant rats increases gene expression of tyrosine hydroxylase and monoamine oxidase in offspring brain.

CONTEXT: Maternal exposure to silver nanoparticles (AgNPs) affects neurobehavioral reflexes and spatial memory formation in offspring. Although the transmission of AgNPs into the brain has been reported, its toxic effect on dopamine metabolism in the brain of offspring has not been studied so far. OBJECTIVE: The aim of the present study was to investigate the expression levels of tyrosine hydroxylase (TH) and monoamine oxidase A (MAO-A) genes in the brain of offspring exposed in utero to various concentrations of AgNPs. MATERIALS AND METHODS: Time mated pregnant adult rats were assigned into three groups including control, low dose of AgNPs (0.2 mg/kg) and high dose of AgNPs (2 mg/kg). AgNPs were subcutaneously (SC) injected at days of 1, 4, 7, 10, 13, 16 and 19 of pregnancy. Gene expression of TH and MAO-A was analyzed in the brain of offspring (male and female) at days of 1, 7, 14 and 21 after birth. RESULTS: Administration of AgNPs to pregnant rats in a time- and dose-dependent manner increased the expression levels of TH in the brain of male and female pups at all tested days after birth (p < 0.05). AgNPs had stimulatory effect on MAO-A mRNA expression in pups only at the age of 7 and 14. Female pups showed the higher level of TH and MAO-A compared to that in male pups (p < 0.001). DISCUSSION AND CONCLUSIONS: Results obtained here demonstrated that the exposure of pregnant rats to AgNPs increases the expression of genes involved in dopamine metabolism in the brain of offspring.

Inhibitory effect of traditional oriental medicine-derived monoamine oxidase B inhibitor on radioresistance of non-small cell lung cancer.

Increased survival of cancer cells mediated by high levels of ionizing radiation (IR) reduces the effectiveness of radiation therapy for non-small cell lung cancer (NSCLC). In the present study, danshensu which is a selected component of traditional oriental medicine (TOM) compound was found to reduce the radioresistance of NSCLC by inhibiting the nuclear factor-κB (NF-κB) pathway. Of the various TOM compounds reported to inhibit the IR activation of NF-κB, danshensu was chosen as a final candidate based on the results of structural comparisons with human metabolites and monoamine oxidase B (MAOB) was identified as the putative target enzyme. Danshensu decreased the activation of NF-κB by inhibiting MAOB activity in A549 and NCI-H1299 NSCLC cells. Moreover, it suppressed IR-induced epithelial-to-mesenchymal transition, expressions of NF-κB-regulated prosurvival and proinflammatory genes, and in vivo radioresistance of mouse xenograft models. Taken together, this study shows that danshensu significantly reduces MAOB activity and attenuates NF-κB signaling to elicit the radiosensitization of NSCLC.

Genetic expression analysis of E2F-associated phosphoprotein in stress responses in the mouse.

Dysfunction of the monoaminergic system is critical in stress and anxiety disorders, but the role of each family member in the development of stress-related psychopathologies is not sufficiently understood. Eapp has been reported to be a transcriptional repressor of monoamine oxidase B (Maob) and down-regulates Maob via the Maob core promoter. In the present study, we more specifically examine the role of Eapp in stress responses by testing the hypothesis that Eapp may be involved in the occurrence and development of stress responses. Western blotting, qPCR and immunohistochemistry were used to investigate the expression variation of Eapp in hypothalamus tissue after exposure to stress. The expression of Eapp is controlled by a cis-acting quantitative trait locus (cis-eQTL). Two genes Sphk2 and Nosip, had trans-eQTLs that mapped to the location of Eapp and altered expression of these two genes was shown following siRNA knockdown of Eapp. Additionally, Mmp9, Npy, Npy5r and Maob were shown to have different expression levels in the Eapp knock-down experiments. Our data provide strong evidence that the cis-modulated gene, Eapp, is associated with stress responses, and that validated downstream targets and members of Eapp gene network may also be involved in the development of stress.

Neurochemical effects of chronic administration of calcitriol in rats.

Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

Genetic variants in renalase and blood pressure responses to dietary salt and potassium interventions: a family-based association study.

BACKGROUND/AIMS: Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies indicate that common variations in the gene with RNLS are associated with hypertension. The aim of this study was to examine the association between genetic variants in RNLS and blood pressure (BP) responses to strict dietary interventions of salt and potassium intake. METHODS: A total of 334 subjects from 124 families were selected and sequentially maintained on a low-salt diet for 7 days (3.0 g/day, NaCl), then a high-salt diet for 7 days (18.0 g/day, NaCl), high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). RESULTS: SNPs rs919115 and rs792205 of the RNLS gene were significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to high-salt intervention. In addition, rs12356177 was significantly associated with systolic BP (SBP) and DBP responses to low-salt diet, and SBP, DBP or MAP during the high-salt intervention. Unfortunately, no associations for the 7 RNLS SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. CONCLUSIONS: This family-based study indicates that genetic variants in the RNLS gene are significantly associated with BP responses to dietary salt intake.

Ameliorative effect of black rice anthocyanin on senescent mice induced by D-galactose.

This study investigated the ameliorative effect of black rice anthocyanin (BACN) in senescent mice induced by D-galactose. The male mice were randomly divided into five groups, namely, the normal group, the model group and dosage groups (15, 30 and 60 mg kg(-1) of BACN). The model group and three dosage groups were continuously injected subcutaneously with D-galactose. The results suggested that superoxide dismutase (SOD) and catalase (CAT) were significantly increased upon black rice anthocyanin treatment, while MDA and the activity of monoamine oxidase (MAO) significantly decreased. The expressions of superoxide dismutase genes (SOD1 and SOD2) in liver were up-regulated in black rice anthocyanin group, while the expression of the MAO-B gene was down-regulated. These findings demonstrated that the ameliorative effect of BACN might be achieved partly by altering endogenous antioxidant enzymatic and aging-related enzymatic activities and regulating SOD1, SOD2 and MAO-B gene expressions.

Candidate SNP associations of optimism and resilience in older adults: exploratory study of 935 community-dwelling adults.

OBJECTIVE: Optimism and resilience promote health and well-being in older adults, and previous reports suggest that these traits are heritable. We examined the association of selected single-nucleotide polymorphisms (SNPs) with optimism and resilience in older adults. DESIGN: Candidate gene association study that was a follow-on at the University of California, San Diego, sites of two NIH-funded multi-site longitudinal investigations: Women's Health Initiative (WHI) and SELenium and vitamin E Cancer prevention Trial (SELECT). PARTICIPANTS: 426 women from WHI older than age 50 years, and 509 men older than age 55 years (age 50 years for African American men) from SELECT. MEASUREMENTS: 65 candidate gene SNPs that were judged by consensus, based on a literature review, as being related to predisposition to optimism and resilience, and 31 ancestry informative marker SNPs, genotyped from blood-based DNA samples and self-report scales for trait optimism, resilience, and depressive symptoms. RESULTS: Using a Bonferroni threshold for significant association (p = 0.00089), there were no significant associations for individual SNPs with optimism or resilience in single-locus analyses. Exploratory multi-locus polygenic analyses with p <0.05 showed an association of optimism with SNPs in MAOA, IL10, and FGG genes, and an association of resilience with a SNP in MAOA gene. CONCLUSIONS: Correcting for Type I errors, there were no significant associations of optimism and resilience with specific gene SNPs in single-locus analyses. Positive psychological traits are likely to be genetically complex, with many loci having small effects contributing to phenotypic variation. Our exploratory multi-locus polygenic analyses suggest that larger sample sizes and complementary approaches involving methods such as sequence-based association studies, copy number variation analyses, and pathway-based analyses could be useful for better understanding the genetic basis of these positive psychological traits.

Low dopamine function in attention deficit/hyperactivity disorder: should genotyping signify early diagnosis in children?

Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor selfesteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with ≥ 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.

Genetic modulation of personality traits: a systematic review of the literature.

The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and personality traits, only modest progress has been made in identifying loci that robustly support these associations. The aim of this study was to provide a summary of literature data on association studies focused on the genetic modulation of personality, according to the Cloninger, Eysenck and Costa and McCrae models. PubMed was searched for papers investigating the association between any gene variant and personality traits, which were grouped into five clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d) socialization and (e) spirituality, in healthy individuals, populations and psychiatric patients. A total of 369 studies were included. No clear consensus on the role of any individual gene variant in personality modulation emerged, although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be more reliably related to anxiety and impulsivity-related traits, respectively. Because conflicting results emerged from the literature, plausibly as a result of the combined influence of many loci of small effects on personality, larger sample sizes and more narrow and specific phenotype will be the minimum requirements for future genetic studies on personality. Moreover, gene × gene and gene × environment interaction studies deserve further attention.