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1.
  • Nilsson, Kent W., et al. (författare)
  • Role of the serotonin transporter gene and family function in adolescent alcohol consumption.
  • 2005
  • Ingår i: Alcoholism. - Uppsala Univ, Clin Res Ctr, Cent Hosp Vasteras, S-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, Pharmacol Unit, S-72189 Vasteras, Sweden. : Wiley-Blackwell Publishing Inc.. - 0145-6008 .- 1530-0277. ; 29:4, s. 564-570
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: That the extent to which a particular individual will engage in problematic behaviors such as delinquency, violence, or drug abuse is determined by the way psychosocial, situational, and hereditary factors interact is widely accepted. However, only recently have researchers begun to investigate the interactions between specific genotypes and psychosocial factors in relation to behavior. The purpose of the present study was to investigate possible interactions between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and family relations on adolescent alcohol consumption.METHODS: A cross-sectional study with a randomized sample from a total population of 16- and 19-year-old adolescents from a Swedish county was conducted. Eighty-one male and 119 female adolescents, who volunteered to participate after having answered a questionnaire, were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behavior.RESULTS: 5-HTT genotype (p=0.029) and family relations (p=0.022) predicted alcohol consumption independently as well as through an interaction with one another (p=0.05). The model explained 11% of the variance in alcohol consumption. In a binary logistic model, we found that adolescents with the LS variant of the 5-HTT gene and with family relations being "neutral" or "bad" had a 12- to 14-fold increased risk for high intoxication frequency.CONCLUSIONS: In sum, our results show that a functional polymorphism of the 5-HTT genotype, family relations, and interactions between these variables predict adolescent alcohol consumption in a randomized sample of adolescents.
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2.
  • Ruchkin, Vladislav V, et al. (författare)
  • Platelet MAO-B, personality, and psychopathology
  • 2005
  • Ingår i: Journal of Abnormal Psychology. - 0021-843X .- 1939-1846. ; 114:3, s. 477-482
  • Tidskriftsartikel (refereegranskat)abstract
    • The article investigates the relationships between platelet monoamine oxidase-B (MAO-B) activity, personality, and psychopathology (Diagnostic and Statistical Manual of Mental Disorders [4th ed.; American Psychiatric Association, 1994] diagnoses. These relationships were assessed in 178 incarcerated male juvenile delinquents. Even after controlling for smoking, the authors found that both Internalizing and Externalizing Psychopathology were negatively related to MAO-B activity. In the final reduced model, novelty seeking fully mediated the relationships between MAO-B and Externalizing Psychopathology but not between MAO-B and Internalizing Psychopathology. It was hypothesized that low platelet MAO-B activity does not directly predispose individuals to psychopathology but is related to specific personality traits, which in turn represent a vulnerability factor for psychopathology. Future studies should help clarify the nature of the relationships between personality, biological markers, and psychopathology.
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3.
  • Comasco, Erika, 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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4.
  • Nilsson, Kent W., et al. (författare)
  • Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity
  • 2006
  • Ingår i: Biological Psychiatry. - Uppsala Univ, Clin Res Ctr, Cent Hosp Vasteras, S-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, Pharmacol Unit, S-72189 Uppsala, Sweden. : Elsevier. - 0006-3223 .- 1873-2402. ; 59:2, s. 121-127
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A number of important sociological, psychological, and biological predictors of adolescent criminal behavior have been identified during the most recent decades. The aim of this study was to replicate recent findings that interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter region and psychosocial factors might predict male adolescent criminal activity.METHODS: A cross-sectional study with a randomized sample from the total population of 16- and 19-year-olds from the county of Västmanland, Sweden. Eighty-one male adolescents, who volunteered to participate, were randomly selected from groups representing different degrees of deviant risk behavior.RESULTS: The present study strongly supports the notion that carrying the 3-repeat allele of the MAO-A-gene promoter increases the risk of male adolescent criminal behavior, when interacting with psychosocial factors. No effects at all of the MAO-A genotype on adolescent criminal activity were found when MAO-A genotype was considered alone (i.e., without its psychosocial context). The explained variance of the bio-psychosocial model (controlling for MAO-A) in this study exceeded the psychosocial model by 12%.CONCLUSIONS: The findings support the notion that genotype and psychosocial factors interact to precipitate male adolescent criminal behavior.
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5.
  • Oreland, Sadia, et al. (författare)
  • Does the transcription factor AP-2beta have an impact on the genetic and early environmental influence on ethanol consumption?
  • 2010
  • Ingår i: Journal of neural transmission. - 0300-9564 .- 1435-1463. ; 117:9, s. 1077-1081
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes involved in alcoholism have consensus sites for the transcription factor activator protein (TFAP) 2beta. In the present study, we investigated TFAP-2beta protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol-avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol-induced TFAP-2beta levels were examined in Wistar rats exposed to different early postnatal environments that are known to affect later ethanol consumption. Taken together, we found differences in brainstem TFAP-2beta protein between the AA and ANA rats.
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6.
  • Oreland, Sadia, et al. (författare)
  • Ethanol-induced effects on the dopamine and serotonin systems in adult Wistar rats are dependent on early-life experiences
  • 2011
  • Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 1405, s. 57-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Some individuals control their ethanol consumption throughout life, but others escalate their intake to levels that increase the risk for addiction. The early environment influences the individual response to ethanol and affects the underlying physiological processes that lead to a transition from a voluntary to a compulsive use of ethanol. However, the neurobiological substrates for these processes are not understood. The present study aimed to test the hypothesis that early environmental experiences affect the neurobiological effects that are induced by voluntary ethanol consumption. Rat pups were subjected to three different rearing environments: conventional animal facility rearing or separation from dam and littermates for either 15 or 360 min. In adulthood, the rats were exposed to a two-bottle free choice between ethanol and water for seven weeks. Tissue levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites were measured in brain areas that have been implicated in reward and addiction processes. Differences in ethanol-induced effects were noted in 5-HT-related measurements in the nucleus accumbens and ventral tegmental area and in dopamine-related measurements in the dorsal raphe nucleus (DRN). These results provided evidence of an early environmental impact on interactive neuronal circuits between the DRN and reward pathways. The amygdala, a key area in addiction processes, was particularly sensitive to early-life conditions. The animals that experienced the longest separation differed from the others; they had low basal 5-HT levels and responded with an increase in 5-HT after ethanol. These altered responses to initial ethanol consumption as a result of early environmental factors may affect the transition from habitual to compulsive drinking and contribute to individual vulnerability or resilience to addiction.
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7.
  • Oreland, Sadia, et al. (författare)
  • Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats
  • 2009
  • Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1305:Suppl. 1, s. S37-S49
  • Tidskriftsartikel (refereegranskat)abstract
    • Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g. ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 minutes (MS15l or MS360l) or individual MS for 15 or 360 minutes (MS15i or MS360i) daily during postnatal days 1-21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15l males had lower 5-HT1A and 5-HT2C receptor mRNA expression at both ages, lower 5-HT2A receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15l females had higher 5-HT2C receptor mRNA expression than the other females. The strong impact of MS15l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short, but not long MS, as evidenced by major differences between MS15l and MS15i. The results suggest that MS15i is less suitable than MS15l to simulate a protective environment in studies of for instance ethanol addiction processes. 
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8.
  • Sjöberg, Rickard L., et al. (författare)
  • Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene
  • 2006
  • Ingår i: International Journal of Neuropsychopharmacology. - Uppsala Univ, Cent Hosp Vasteras, Clin Res Ctr, S-72189 Vasteras, Sweden. Univ Uppsala, Pharmacol Unit, Dept Neurosci, Uppsala, Sweden. : CAMBRIDGE UNIV PRESS. - 1461-1457 .- 1469-5111. ; 9:4, s. 443-449
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.
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9.
  • Nilsson, Kent W, et al. (författare)
  • Interaktioner mellan gener och miljö. Predicerar kriminalitet, depression och alkoholberoende
  • 2006
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:39, s. 2859-2863
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently interactions between promoter polymorphisms in the serotonin transporter gene and the Monoamine oxidase-A gene have been found to interact with psychosocial factors to predict outcome such as adolescent criminal behaviour, alcohol consumption and depression. In this paper we review this emerging field of scientific inquiry with particular attention paid to findings made on a population based sample of 119 girls and 81 boys from the county of Västmanland, Sweden.
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10.
  • Sjöberg, Rickard L, et al. (författare)
  • Development of depression : sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene.
  • 2006
  • Ingår i: International Journal of Neuropsychopharmacology. - 1461-1457 .- 1469-5111. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.
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