Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness
ABSTRACT A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.
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ABSTRACT: The oxidative imbalance appears to have an important role in anxiety development. Studies in both humans and animals have shown a strong correlation between anxiety and oxidative stress. In humans, for example, the increased malondialdehyde levels and discrepancies in antioxidant enzymes in erythrocytes have been observed. In animals, several studies also show that anxiety-like behavior is related to the oxidative imbalance. Moreover, anxiety-like behavior can be caused by pharmacological-induced oxidative stress. Studies using knockout or overexpression of antioxidant enzymes have shown a relationship between anxiety-like behavior and oxidative stress. Related factors of oxidative stress that could influence anxious behavior are revised, including impaired function of different mitochondrial proteins, inflammatory cytokines, and neurotrophic factors. It has been suggested that a therapy specifically focus in reducing reactive species production may have a beneficial effect in reducing anxiety. However, the neurobiological pathways underlying the effect of oxidative stress on anxiety symptoms are not fully comprehended. The challenge now is to identify the oxidative stress mechanisms likely to be involved in the induction of anxiety symptoms. Understanding these pathways could help to clarify the neurobiology of the anxiety disorder and provide tools for new discovery in therapies and preventive strategies.Current Neuropharmacology 03/2014; 12(2):193-204. DOI:10.2174/1570159X11666131120223530 · 2.35 Impact Factor
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ABSTRACT: Objective Monoamine oxidase A (MAOA) gene promoter region includes a variable number of tandem repeat (VNTR) associated with antisocial behaviour in adverse environment. We have examined the effect of the MAOA-uVNTR on mental health and academic success by using a population representative sample and a longitudinal design. Methods The data of the older cohort (n = 593, aged 15 years at the original sampling) of the longitudinal Estonian Children Personality, Behaviour and Health Study (ECPBHS) were used. Follow-ups were conducted at ages 18 and 25 years. Aggressiveness, inattention and hyperactivity were reported by class teachers or, at older age, self-reported. Stressful life events, psychological environment in the family and interactions between family members were self-reported. Data of general mental abilities and education were obtained at the age of 25, and lifetime psychiatric disorder assessment was carried out with the Mini-International Neuropsychiatric Interview (MINI) interview. Results MAOA-uVNTR genotype had no independent effect on aggressiveness, hyperactive and inattentive symptoms, and neither was there a genotype interaction with adverse life events. Interestingly, the proportion of male subjects with higher education by the age of 25 was significantly larger among those with MAOA low-activity alleles (χ2 = 7.13; p = 0.008). Logistic regression revealed that MAOA low-activity alleles, higher mental abilities, occurrence of anxiety disorders and absence of substance-use disorder were significant independent predictors for higher education in male subjects. Conclusions In a population representative sample of young subjects, the MAOA-uVNTR ‘risk genotype’ predicted better life outcomes as expressed in higher level of education.Acta Neuropsychiatrica 02/2014; 26(01):19-28. DOI:10.1017/neu.2013.34 · 0.64 Impact Factor
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ABSTRACT: NO is a gaseous transmitter produced by nitric oxide synthases (NOSs). The neuronal isoform (NOS-I, encoded by NOS1) is the main source of NO in the CNS. Animal studies suggest that nitrinergic dysregulation may lead to behavioral abnormalities. Unfortunately, the large number of animal studies is not adequately reflected by publications concerning humans. These include postmortem studies, determination of biomarkers, and genetic association studies. Here, we review the evidence for the role of NO in psychiatric disorders by focusing on the human NOS1 gene as well as biomarker studies. Due to the complex regulation of NOS1 and the varying function of NOS-I in different brain regions, no simple, unidirectional association is expected. Rather, the "where, when and how much" of NO formation is decisive. Present data, although still preliminary and partially conflicting, suggest that genetically driven reduced NO signaling in the prefrontal cortex is associated with schizophrenia and cognition. Both NOS1 and its interaction partner NOS1AP have a role therein. Also, reduced NOS1 expression in the striatum determined by a length polymorphism in a NOS1 promoter (NOS1 ex1f-VNTR) goes along with a variety of impulsive behaviors. An association of NOS1 with mood disorders, suggested by animal models, is less clear on the genetic level; however, NO metabolites in blood may serve as biomarkers for major depression and bipolar disorder. As the nitrinergic system comprises a relevant target for pharmacological interventions, further studies are warranted to elucidate the pathophysiology of mental disorders, but also to evaluate NO function as a biomarker. This article is protected by copyright. All rights reserved.Genes Brain and Behavior 01/2015; 14(1). DOI:10.1111/gbb.12193 · 3.51 Impact Factor