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Träfflista för sökning "WFRF:(Comasco Erika) ;lar1:(oru)"

Sökning: WFRF:(Comasco Erika) > Örebro universitet

  • Resultat 1-6 av 6
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1.
  • Comasco, Erika, 1982-, et al. (författare)
  • Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
  • 2017
  • Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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2.
  • Isaksson, Johan, et al. (författare)
  • Associations between the FKBP5 haplotype, exposure to violence and anxiety in females
  • 2016
  • Ingår i: Psychoneuroendocrinology. - Oxford, United Kingdom : Elsevier. - 0306-4530 .- 1873-3360. ; 72, s. 196-204
  • Tidskriftsartikel (refereegranskat)abstract
    • The gene that encodes the FK506-binding protein 5 (FKBP5) is regarded as a candidate for investigating how negative life events interact with a genetic predisposition to stress-related disorders, such as depression and anxiety. Given the role of FKBP5 as an important regulator of stress responses, we aimed to investigate if single-nucleotide polymorphisms (SNPs) in FKBP5-in the presence/absence of exposure to violence-are associated with symptoms of depression and anxiety. Data from two community-based samples of adolescents (n=1705) and young adults (n=1800) regarding ratings on depression, anxiety, exposure to violence and FKBP5 genotype were collected. A risk haplogenotype including the minor alleles of seven common SNPs in the FKBP5 (rs3800373, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080 and rs4713916) conferred higher ratings on anxiety among females, but not males, in the presence of violence. Exposure to violence and female sex were associated with higher ratings on both depression and anxiety, with the exception of ratings on depression among young adults, on which sex had no effect. Ratings on depression were not associated with the haplogenotype. These findings may correspond to differences in the regulation of the HPA axis and with the higher vulnerability to anxiety in females.
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3.
  • Nylander, Ingrid, 1957-, et al. (författare)
  • Evidence for a Link Between Fkbp5/FKBP5, Early Life Social Relations and Alcohol Drinking in Young Adult Rats and Humans
  • 2017
  • Ingår i: Molecular Neurobiology. - : Humana Press. - 0893-7648 .- 1559-1182. ; 54:8, s. 6225-6234
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans. In rats, Fkbp5 expression in the nucleus accumbens and ventral tegmental area, core regions of the reward system, was affected in a region-dependent manner and in opposite direction by maternal separation and alcohol drinking. Fkbp5 expression in the cingulate cortex was affected by the combined effect of maternal separation and alcohol drinking. In humans, the TT genotype, in the presence of a poor relationship between the child and parents, was associated with problematic drinking behavior. The present findings suggest that Fkbp5 expression in mesocorticolimbic dopaminergic regions associates with early life stress-mediated sensitivity to alcohol drinking and that FKBP5 genotype interacts with parent-child relationship to influence alcohol drinking. These findings are the first to point to a role of FKBP5 in propensity to alcohol misuse and call for studies of the underlying molecular mechanisms to identify potential drug targets.
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4.
  • Tuvblad, Catherine, 1968-, et al. (författare)
  • Physical and verbal aggressive behavior and COMT genotype : Sensitivity to the environment
  • 2016
  • Ingår i: American Journal of Medical Genetics Part B. - Hoboken, USA : John Wiley & Sons. - 1552-4841 .- 1552-485X. ; 171:5, s. 708-718
  • Tidskriftsartikel (refereegranskat)abstract
    • Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples.
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5.
  • Vrettou, Maria, et al. (författare)
  • VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths
  • 2019
  • Ingår i: European Child and Adolescent Psychiatry. - : Springer. - 1018-8827 .- 1435-165X. ; 28:10, s. 1329-1340
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors. Three samples were included: a clinical sample of 131 adolescents followed from age 17 to 22; a general population sample of 1794 young adults; and a general population sample of 1687 adolescents followed from age 14 to 17. DNA was extracted from saliva and the rs2290045 (T/C) was genotyped. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test. Stressful life events (SLE) and parenting were assessed by questionnaires. Gene-environment interactions were investigated using a dual statistical approach. In all samples (effect sizes 0.6-6.2%), and consistent with the differential susceptibility framework, T carriers exposed to SLE reported more alcohol-related problems if they had experienced poor parenting, and lower alcohol-related problems if they had received supportive parenting. T carriers not exposed to SLE reported higher alcohol-related problems if they had received supportive parenting and lower alcohol-related problems if they had received poor parenting. Among CC carriers, alcohol-related problems did not vary as a function of negative and positive environmental factors. In conclusion, in three samples of youths, alcohol-related problems were associated with an interaction of VGLUT2 rs2290045, SLE, and parenting.
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6.
  • Vrettou, Maria, et al. (författare)
  • VGLUT2 genotype interacts with environmental experiences to predict alcohol misuse in young adults
  • 2016
  • Ingår i: ISBRA ESBRA World Congress on Alcohol an Alcoholism, Berlin, Germany.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The heritability of alcohol use disorder (AUD) ranges between 40 to 60%, as demonstrated by twin studies. Environmental factors are hence of importance for the developmental trajectory of the disorder. Gene-by-environment interactions indeed influence neuroplasticity and determine the individual’s susceptibility or resilience to AUD. Lately, a role of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been indicated in studies of addiction- and alcohol-related phenotypes. We previously demonstrated an association between the single nucleotide polymorphism (SNP) rs2290045 in the VGLUT2 gene and alcohol dependence as well as showed an interaction effect between voluntary ethanol drinking and early life stress on Vglut2 expression in the ventral tegmental area of outbred rats. In the present study, using a population-based, cross-sectional and retrospective design, we aimed to investigate the association between two candidate VGLUT2 SNPs, rs1900586 and rs2290045, and aversive as well as supportive environmental factors on alcohol misuse in young adults. A total of 2,500 (52.6% females) individuals (mean age: 22.15 years) were included in the study. Aversive life events (i.e., physical violence, verbal aggression, witnessing violence) and parent-child relationship (i.e., early: until 18 years of age; lifetime: until present) were self-reported. Alcohol misuse was assessed using the AUD Identification Test (AUDIT). Preliminary results showed no main genotype effects on drinking profile. Multivariable analyses revealed that SNP rs1900586 interacted with exposure to verbal aggression and early parent-child relationship in respect to AUDIT scores. Male carriers of the major (T) allele reported higher AUDIT scores when exposed to verbal aggression and poor early parent-child relationship than the C carriers exposed to the same environment, while the opposite pattern was noted in the presence of supportive parent-child relationship. In individuals with symptoms of dependence or harmful alcohol use, SNP rs1900586 interacted with exposure to physical violence and parent-child relationship (early and lifetime) in both sexes. The same interaction effect was detected for SNP rs2290045 in females. These preliminary findings provide the first evidence that VGLUT2 genotype moderates the environmental sensitivity to alcohol misuse among young adults and call for further investigation in independent cohorts, including clinical samples.
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