| 1. |
- Gokturk, Camilla, et al.
(författare)
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Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism
- 2008
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Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 11:5-6, s. 347-355
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin system is known to play a pivotal role for mood, behaviour and psychic illness as e.g. alcoholism. Alcoholism in both males and females has been associated with polymorphisms in genes encoding for proteins of importance for central serotonergic function. Genotyping of two functional polymorphisms in the promoter region of the serotonin transporter and monoamine oxidase-A, respectively, (5-HTT-LPR and MAOA-VNTR), was performed in a group of women with severe alcohol addiction. A large sample of adolescent females from a normal population was used as controls. A significantly higher frequency of the LL 5-HTT genotype (high activity) was found in female addicts without a known co-morbid psychiatric disorder than in the controls. Genotype of the MAOA-VNTR polymorphism did not differ significantly between addicts and controls. However, within the group of alcoholics, when the patients with known co-morbid psychiatric disorders were excluded, aggressive anti-social behaviour was significantly linked to the presence of the high activity MAOA allele. The pattern of associations between genotypes of 5-HTT-LPR and MAOA-VNTR in women with severe alcoholism differs from most corresponding studies on males.
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| 2. |
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| 3. |
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| 4. |
- Oreland, Sadia, et al.
(författare)
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Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats
- 2009
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1305:Suppl. 1, s. S37-S49
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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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| 5. |
- Akkermann, Kirsti, et al.
(författare)
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Association of 5-HTT gene polymorphism, platelet MAO activity, and drive for thinness in a population-based sample of adolescent girls
- 2008
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Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 41:5, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects. METHOD: The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales--Drive for Thinness and Bulimia--were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR. RESULTS: Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness. CONCLUSION: The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity.
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| 6. |
- Berggard, Cecilia, et al.
(författare)
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Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram
- 2005
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Ingår i: BMC Pharmacology. - : Springer Science and Business Media LLC. - 1471-2210. ; 5, s. 1-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Before therapeutic effect is obtained after treatment with antidepressant drugs, like serotonin selective reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO-Is) there is an initial lag-period of a few weeks. Neuronal adaptations on a molecular level are supposed to be involved in the initiation of the antidepressant effect. Transcription factor AP-2 is essential for neuronal development and many genes involved in the brainstem monoaminergic systems have binding sites for AP-2 in their regulatory regions. The genotype of the AP-2beta isoform has been associated with e.g. anxiety-related personality traits and with platelet MAO activity. In addition, previous studies have shown that the levels of AP-2alpha and AP-2beta in rat whole brain were decreased after 10 days of treatment with citalopram (SSRI) and imipramine (TCA), and were increased with phenelzine (MAO-I). RESULTS: In the present study, we report that treatment with citalopram for 1, 7 or 21 days did not have effect on the AP-2 levels in rat brainstem. However, after treatment with phenelzine for 1, 7 or 21 days the levels of AP-2alpha and AP-2beta had increased after 7 days, but had returned to control levels at day 21. CONCLUSION: The decrease in AP-2 levels in rat whole brain previously seen after treatment with citalopram does not seem to be localised to the brainstem, it may rather occur in the monoaminergic terminal projection areas. The present data suggest that the increase in AP-2 levels previously seen in rat whole brain after subchronic treatment with phenelzine is located in the brainstem. It cannot, however, be excluded that other brain regions are involved.
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| 7. |
- Birgner, Carolina, et al.
(författare)
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Reduced activity of monoamine oxidase in the rat brain following repeated nandrolone decanoate administration
- 2008
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1219, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Anabolic androgenic steroids (AAS) are known as doping agents within sports and body-building, but are currently also abused by other groups in society in order to promote increased courage and aggression. We previously showed that 14 days of daily intramuscular injections of the AAS nandrolone decanoate (15 mg/kg) reduced the extracellular levels of the dopaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens shell using microdialysis. The aim of the present study was to investigate whether the same dose regimen of nandrolone decanoate may affect the activities of the dopamine-metabolizing enzymes monoamine oxidases A and B (MAO-A and MAO-B). A radiometric assay was used to determine the activities of MAO-A and MAO-B in rat brain tissues after 14 days of daily i.m. nandrolone decanoate injections at the doses 3 and 15 mg/kg. Gene transcript contents of MAO-A, MAO-B and cathecol-O-methyltransferase (COMT) were measured with quantitative real-time reverse transcription PCR. 3 mg/kg of nandrolone decanoate significantly reduced the activity of both MAO-A and -B in the caudate putamen. 15 mg/kg of nandrolone decanoate significantly reduced the activity of MAO-A in the amygdala and increased the gene transcript level of MAO-B in the substantia nigra. In conclusion, imbalanced MAO activities may contribute to explain the impulsive and aggressive behaviour often described in AAS abusers. The reduced MAO activities observed are in line with our previously presented findings of decreased extracellular levels of DOPAC and HVA in the rat brain, indicating decreased monoaminergic activity following repeated AAS administration.
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| 8. |
- Comasco, Erika, et al.
(författare)
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Adolescent alcohol consumption : Biomarkers PEth and FAEE in relation to interview and questionnaire data
- 2009
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Ingår i: Journal of Studies on Alcohol and Drugs. - : ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV. - 1937-1888 .- 1938-4114. ; 70:5, s. 797-804
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption. METHOD The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively. RESULTS High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls. CONCLUSIONS The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.
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| 9. |
- Fetissov, Sergueï O, et al.
(författare)
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Aggressive behavior linked to corticotropin-reactive autoantibodies
- 2006
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 60:8, s. 799-802
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS: Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS: Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS: High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.
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| 10. |
- Furmark, Tomas, et al.
(författare)
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A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:49, s. 13066-74
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Tidskriftsartikel (refereegranskat)abstract
- Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond to placebo are widely unknown. Here, we used functional neuroimaging to examine neural correlates of anxiety reduction resulting from sustained placebo treatment under randomized double-blind conditions, in patients with social anxiety disorder. Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period. Patients were genotyped with respect to the serotonin transporter-linked polymorphic region (5-HTTLPR) and the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene promoter. Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing. However, attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703T polymorphism, and not in carriers of short or T alleles. Moreover, the TPH2 polymorphism was a significant predictor of clinical placebo response, homozygosity for the G allele being associated with greater improvement in anxiety symptoms. Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity. Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.
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| 11. |
- Furmark, Tomas, et al.
(författare)
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Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.
- 2009
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Ingår i: Journal of psychiatry & neuroscience : JPN. - : Canadian Medical Association. - 1488-2434 .- 1180-4882. ; 34:1, s. 30-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)-related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls. METHODS: We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms. RESULTS: Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles. LIMITATIONS: Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrollment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli. CONCLUSION: Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.
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| 12. |
- Gokturk, Camilla, et al.
(författare)
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Macrovascular changes in mice overexpressing human semicarbazide-sensitive amine oxidase in smooth muscle cells
- 2007
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 20:7, s. 743-750
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Tidskriftsartikel (refereegranskat)abstract
- Background: The catalytic activity of semicarbazide-sensitive amine oxidase (SSAO) is increased in diabetes, as well as in other disorders of cardiovascular origin. Our hypothesis is that SSAO is involved in the synthesis or maturation of elastin in vascular tissue. An increased SSAO activity can thereby be involved in the development of vascular damage. Methods: Elastin quantification was performed in aorta of transgenic mice overexpressing the human form of SSAO, using electron microscopy. Furthermore, lung capacity was measured using a spirometry-mimicking method, developed for mice. The effect of vasoactive substances was estimated by measuring mean arterial pressure and pulse pressure under anesthesia. Results: No differences in elastin quantity or lung capacity could be observed between transgenic or nontransgenic littermates. Pulse pressure was higher in transgenic mice, and electron microscopy of aorta showed elastin fibers parallel with the aorta wall (ie, straight fibers instead of folded compared with control mice). No difference in the response to adrenaline or sodium chloride was observed between the transgenic and control mice. The control mice had a clear decrease in blood pressure (BP) with a longer duration as a response to injection of a nitric oxide (NO) donor, sodium nitroprusside, compared with transgenic mice where only a minor response was observed. The SSAO activity in serum of control mice was elevated in response to injection of the NO donor, but not in response to a ganglion blocker. Conclusions: An elevated pulse pressure, together with an abnormal elastin structure in the aorta, suggests a rigidity of large arteries as a result of an elevated SSAO activity as well as a physiologic role for SSAO in elastin maturation.
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| 13. |
- Grigorenko, Elena L., et al.
(författare)
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Exploring interactive effects on genes and environments in etiology of individual differences in reading comprehension
- 2007
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Ingår i: Development and Psychopathology. - 0954-5794 .- 1469-2198. ; 19:4, s. 1089-1103
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Tidskriftsartikel (refereegranskat)abstract
- It is established that reading and reading-related processes are heritable; genes thus play an important role in the foundation of individual differences in reading. In this article, we focus on one facet of reading–comprehension. Comprehension is a higher order cognitive skill that requires many other cognitive processes for it to unfold completely and successfully. One such process is executive functioning, which has been associated with genetic variation in the catechol-O-methyltransferase (COMT) gene. Genotypes and haplotypes of four single nucleotide polymorphisms in COMT were investigated in 179 incarcerated adolescent delinquents. Four hierarchical logistic regression models predicting the presence/absence of comprehension difficulties were fitted to the data; genetic variation in COMT and the presence/absence of maternal rejection were investigated as main effects and as effects acting interactively. Three out of four interaction terms were found to be important predictors of individual differences in comprehension. These findings were supported by the results of the haplotype analyses, in which the four investigated polymorphisms were considered simultaneously.
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| 14. |
- Haeffel, Gerald J., et al.
(författare)
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Association Between Polymorphisms in the Dopamine Transporter Gene and Depression : Evidence for a Gene-Environment Interaction in a Sample of Juvenile Detainees
- 2008
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Ingår i: Psychological Science. - : SAGE Publications. - 0956-7976 .- 1467-9280. ; 19:1, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has generated examples of how genetic and environmental factors can interact to create risk for psychopathology. Using a gene-by-environment (G × E) interaction design, we tested whether three polymorphisms in the dopamine transporter gene (DAT1, also referred to as SLC6A3, located at 5p15.33) interacted with maternal parenting style to predict first-onset episodes of depression. Participants were male adolescents (N= 176) recruited from a juvenile detention center in northern Russia. As hypothesized, one of the polymorphisms (rs40184) moderated the effect of perceived maternal rejection on the onset of major depressive disorder, as well as on suicidal ideation. Further, this G × E interaction was specific to depression; it did not predict clinically significant anxiety. These results highlight the need for further research investigating the moderating effects of dopaminergic genes on depression.
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| 15. |
- Harro, Jaanus, et al.
(författare)
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Personality and the serotonin transporter gene : Associations in a longitudinal population-based study
- 2009
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Ingår i: Biological Psychology. - : Elsevier BV. - 0301-0511 .- 1873-6246. ; 81:1, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- Associations between the promoter polymorphism of the serotonin transporter gene (5-HTTLPR) and anxiety-related personality traits in healthy adult subjects have been inconsistent. We assessed personality in participants of the Estonian Children Personality Behaviour and Health Study, using parental reports and self-reports. In the younger cohort, according to parental assessments at ages 9 and 15, children homozygous for the S allele had significantly higher scores of Neuroticism and lower scores of Openness, Agreeableness and Conscientiousness. Parental assessment of the older cohort at ages 15 and 18 did not yield any genotype effect on personality; however, interaction of cohort and genotype was not significant. According to self-reports, SS homozygotes had higher Neuroticism at age 15 but not at age 18. Thus, homozygocity for the S allele of the 5-HTTLPR is related to anxiety-related personality traits in general population, but this is easier to detect before adolescence.
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| 16. |
- Hensch, Tilman, et al.
(författare)
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Electrophysiological and behavioral correlates of polymorphisms in the transcription factor AP-2beta coding gene
- 2008
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 436:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factor AP-2beta may influence brain monoaminergic systems by regulating target genes. Several monoaminergic genes, including the serotonin transporter gene, have AP-2beta binding sites. Late auditory-evoked potentials (P1, N1/P2) and impulsiveness-related personality traits are correlated, and both are modulated by monoaminergic neurotransmission. The present study assesses the impact of two AP-2beta polymorphisms (VNTRs within intron 1 and 2) together with the serotonin transporter polymorphism 5-HTTLPR on late auditory-evoked potentials and personality for the first time. EEG was recorded from 91 male subjects at central electrode positions while tones of six intensity levels were presented. Additionally, subjects completed personality questionnaires. Both AP-2beta polymorphisms revealed significant main effects on P1, and haplotype analysis confirmed the contribution of both AP-2beta-polymorphisms. Additionally, AP-2beta and 5-HTTLPR showed interactions with respect to P1. 5-HTTLPR revealed a main effect on N1/P2 but not P1. Impulsiveness showed an association with intron 1 VNTR. The results are discussed with respect to differential impact of AP-2beta polymorphisms and 5-HTTLPR on the monoaminergic systems. The findings promote replication in a larger sample and suggest a potential usefulness of AP-2beta polymorphisms in explaining or predicting central nervous diseases, drug effects and side effects.
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| 17. |
- Hensch, Tilman, et al.
(författare)
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Further evidence for an association of 5-HTTLPR with intensity dependence of auditory-evoked potentials
- 2006
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X .- 1740-634X. ; 31:9, s. 2047-2054
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Tidskriftsartikel (refereegranskat)abstract
- Intensity dependence of auditory-evoked potentials (IAEP) has been suggested as an indicator of central serotonergic neurotransmission. Two recent studies investigated a possible association of IAEP with a functional polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) that has a short (s) and a long (l) variant. Although both studies found an association between 5-HTTLPR and IAEP, Gallinat et al found l/l individuals to exhibit lower IAEP, whereas Strobel et al observed stronger IAEP in l/l individuals. These conflicting results require further evaluation and more attention needs to be paid to variables that are known to be confounded with the effects of IAEP and 5-HTTLPR. Using a paradigm comparable to Strobel et al, the present study analyzes the effect of 5-HTTLPR on IAEP in a healthy male student sample (N=91; age=23 years, SD=1.9) that was homogenous for most significant confounding variables. A stronger IAEP was shown in l/l individuals, irrespective of the method of IAEP parametrization. This also held at retest after 3 weeks in a subsample (N=18). Given the successful replication of Strobel et al, several possible reasons for conflicting results with regard to Gallinat et al are discussed. It is argued that the most significant difference between Gallinat et al on the one hand, and Strobel et al and this study on the other, is that different intensity ranges are used which impact IAEP. Therefore, this study encourages further analysis of dose dependence of results.
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| 18. |
- Lawrence, K., et al.
(författare)
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The development of mental state attributions in women with X-monosomy, and the role of monoamine oxidase B in the sociocognitive phenotype
- 2007
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Ingår i: Cognition. - : Elsevier BV. - 0010-0277 .- 1873-7838. ; 102:1, s. 84-100
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that women with Turner syndrome (45,X) with a single X-chromosome inherited from their mother may show mentalizing deficits compared to women of normal karyotype with two X-chromosomes (46,X). Simple geometrical animation events (two triangles moving with apparent intention in relation to each other) which usually elicit mental-state descriptions in normally developing people, did not do so to the same extent in women with Turner syndrome. We then investigated the potential role in this deficit played by monoamine oxidase B enzymatic activity. MAO-B activity reflects central serotonergic activity, and by implication the functional integrity of neural circuits implicated in mentalizing. Platelet MAO-B was substantially reduced in Turner syndrome. However, contrary to prediction, in this (relatively small) sample there was no association between MAO-B enzymatic activity and mentalizing skills in participants with and without Turner syndrome.
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| 19. |
- Malmberg, Kerstin, et al.
(författare)
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ADHD and Disruptive Behavior scores - associations with MAO-A and 5-HTT genes and with platelet MAO-B activity in adolescents
- 2008
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Ingår i: BMC Psychiatry. - 1471-244X. ; 8, s. 28-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorder (DBD). We have, in a population-based sample, studied associations between dimensions of the ADHD/DBD phenotype and Monoamine Oxidase B (MAO-B) activity in platelets and polymorphisms in two serotonergic genes: the Monoamine Oxidase A Variable Number of Tandem Repeats (MAO-A VNTR) and the 5-Hydroxytryptamine Transporter gene-Linked Polymorphic Region (5-HTT LPR). METHODS: A population-based sample of twins, with an average age of 16 years, was assessed for ADHD/DBD with a clinical interview; Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Blood was drawn from 247 subjects and analyzed for platelet MAO-B activity and polymorphisms in the MAO-A and 5-HTT genes. RESULTS: We found an association in girls between low platelet MAO-B activity and symptoms of Oppositional Defiant Disorder (ODD). In girls, there was also an association between the heterozygote long/short 5-HTT LPR genotype and symptoms of conduct disorder. Furthermore the heterozygote 5-HTT LPR genotype in boys was found to be associated with symptoms of Conduct Disorder (CD). In boys, hemizygosity for the short MAO-A VNTR allele was associated with disruptive behavior. CONCLUSION: Our study suggests that the serotonin system, in addition to the dopamine system, should be further investigated when studying genetic influences on the development of Disruptive Behavior Disorders.
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| 20. |
- Nilsson, Kent W., 1964-
(författare)
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Gene-Environment Interaction in Adolescent Deviant Behaviour
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to explore gene-environmental (G*E) interactions in relation to deviant behaviour among 200 Swedish adolescents, with a focus on criminality, alcohol consumption and depressive symptoms. Those behaviours have been extensively investigated in relation to both psychosocial and biological risk factors. The biological markers used were the monoamine oxidase (MAO-A) and serotonin transporter (5-HTTLPR) gene polymorphisms. The main findings indicated a considerable gene-environment interaction in relation to all outcome variables studied. Individuals with the long/short variant of the 5HTTLPR gene, in combination with unfavourable family relations, both consumed more alcohol and had 12-14 times higher risks of being classified as high alcohol consumers. The MAO-A gene showed a G*E interaction related to criminality. Among boys, the short allele predicted an increased risk for criminality, whereas among girls, it was the long allele, if they lived in multi-family houses and/or had been maltreated, assaulted or sexually abused. A G*E interaction in relation to depressive symptoms among both boys and girls was determined. Girls carrying the short 5HTTLPR allele in combination with psychosocial stress, presented elevated depressive symptoms, whereas among boys, the long 5HTTLPR allele was a source of depressive symptoms. In both sexes, there was a G*E interaction of a psychosocial risk index. Girls were more affected by poor family relations and boys by multi-family housing and separated parents. In conclusion, the MAO-A and 5HTTLPR genotypes, in interaction with psychosocial adversity, are related to different deviant behaviours among adolescents. The direct effects of the genotypes needed to be adjusted for the psychosocial factors, whereas the psychosocial factors had direct relation to the outcome measures. There is also an indication of a different pattern in G*E interaction between boys and girls and that different psychosocial factors affect boys and girls differently.
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| 21. |
- Nilsson, Kent W., et al.
(författare)
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Genes encoding for AP-2beta and the Serotonin Transporter are associated with the Personality Character Spiritual Acceptance
- 2007
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Ingår i: Neuroscience Letters. - Uppsala Univ, Cent Hosp Vasteras 1, Ctr Clin Res, SE-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, BMC, SE-75124 Uppsala, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Lund Univ, Univ Hosp Malmo, Forens Psychiat Clin, SE-20502 Malmo, Sweden. : Elsevier BV. - 0304-3940 .- 1872-7972. ; 411:3, s. 233-237
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Tidskriftsartikel (refereegranskat)abstract
- In several twin studies the relative contribution of genetic factors for personality traits has amounted to figures between 40 and 60%. In the present study we investigated to which degree polymorphisms in the 5-HTT and AP-2beta genes are implicated in the neural processes involved in the formation of Temperament and Character traits, as estimated by Cloninger's TCI. Considering the background of previous reports, associations with the character Self-Transcendence and its sub-scale Spiritual Acceptance in particular, were of interest. A stratified random sample of 200 individuals (total population=5173), matched for age, gender and risk behaviors, from volunteering 16- and 19-year-old adolescents students in Sweden was investigated. Cloninger's TCI inventory was used for investigation of temperament and character traits. Blood samples were used for analyses of a promoter serotonin transporter polymorphism (5-HTTLPR) and an intron 2 polymorphism in the transcription factor AP-2beta gene. Among boys individuals with presence of the short 5-HTTLPR genotype showed lower scores, whereas individuals with presence of the short AP-2beta genotype showed higher scores of personality character Self-Transcendence and its sub-scale Spiritual Acceptance. Among girls no effect of either genotype was found. Both among boys and girls, significant interactive effects were found between 5-HTTLPR and AP-2beta genotypes, with regard to Self-Transcendence and Spiritual acceptance. Boys and girls with the combination of presence of the short 5-HTTLPR, and homozygosity for the long AP-2beta genotype scored significantly lower on Self-Transcendence and Spiritual Acceptance.
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| 22. |
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| 23. |
- Nilsson, Kent W, et al.
(författare)
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Interaktioner mellan gener och miljö. Predicerar kriminalitet, depression och alkoholberoende
- 2006
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:39, s. 2859-2863
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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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| 24. |
- Nilsson, Kent W., et al.
(författare)
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Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity
- 2006
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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
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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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| 25. |
- Nilsson, Kent W., et al.
(författare)
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Role of the serotonin transporter gene and family function in adolescent alcohol consumption.
- 2005
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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
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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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| 26. |
- Nilsson, Kent W, et al.
(författare)
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Smoking as a product of gene-environment interaction
- 2009
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 114:2, s. 100-107
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Tidskriftsartikel (refereegranskat)abstract
- A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples. A random Swedish adolescent population sample (n = 785), from which 200 individuals were stratified regarding behaviour, was genotyped for 5-HTTLPR and assessed with semi-structured interviews, a questionnaire, and hair analyses of nicotine and cotinine. The 5-HTTLPR gene interacted with a poor family environment to predict smoking habits, as well as nicotine and cotinine levels. The risk of being a smoker was increased 13 times for an individual with a combination of the 5-HTTLPR LS genotype and a poor family environment in comparison with the Homozygous Long-Long (LL) genotype and a good family environment.
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| 27. |
- Nilsson, Kent W, et al.
(författare)
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The MAO-A gene, platelet MAO-B activity and psychosocial environment in adolescent female alcohol-related problem behaviour
- 2008
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Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 93:1-2, s. 51-62
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antisocial behaviour has been associated with polymorphic variants in candidate genes and recently also gene-environmental interaction models have been presented. It has been suggested that antisocial behaviour, associated with alcohol consumption in males, is related to a variation in the monoamine oxidase A gene (MAO-A) promoter. Furthermore, platelet MAO-B activity has in several studies been reported to be low in male alcoholics, while this has not been the case with regard to female alcoholics. Aims of the present study were to: (1) investigate possible interactions between the MAO-A polymorphism, family relations and maltreatment/sexual abuse on adolescent alcohol-related problem behaviour among female adolescents; (2) to investigate if platelet MAO-B enzyme activity interacted with environment to predict female alcohol-related problems. Methods: A random sample of 114 female individuals from a total population of 16- and 19-year adolescents from a Swedish county, who volunteered to participate in the study, were interviewed, filled in a questionnaire and a blood sample was drawn. Results: In contrast to what has been reported in males, presence of the long (4-repeat) variant of the MAO-A gene in females interacted significantly with an unfavourable environment (poor family relations or maltreatment/abuse/sexual abuse) to increase the risk for high scores of alcohol-related problems. Furthermore, females with low platelet MAO-B activity showed an increased risk of alcohol-related problem behaviour in an unfavourable environment. Conclusions: Poor psychosocial environment interacts with the high activity MAO-A genotype and low platelet MAO-B enzyme activity to increase vulnerability for female adolescent alcohol-related problem behaviour.
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| 28. |
- Nilsson, Kent W., et al.
(författare)
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The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumption
- 2007
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Ingår i: Addiction. - Uppsala Univ, Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden. Uppsala Univ, Pharmacol Unit, Dept Neurosci, Uppsala, Sweden. : Wiley. - 0965-2140 .- 1360-0443. ; 102:3, s. 389-398
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate possible interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter, family relations and maltreatment/sexual abuse on adolescent alcohol-related problem behaviour among male adolescents. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study of a randomized sample of 66 male individuals from a total population of 16- and 19-year adolescents from a Swedish county. Boys, who volunteered to participate answering an alcohol-related problem/behaviour questionnaire, were investigated with regard to interactions between such problems, family function, maltreatment and MAO-A genotype. MEASUREMENTS: MAO-A genotype, family relations history, history of being maltreated or abused and alcohol-related problem behaviour. FINDINGS: Boys with the short (three-repeat) variant of the MAO-A gene, who had been maltreated/abused or came from families with poor relations, showed significantly higher scores of alcohol-related problems. We also found that maltreatment/abuse independently showed the strongest relation to alcohol-related problems among boys in our model. CONCLUSIONS: The results suggest that both maltreatment and MAO-A genotype may be useful for the understanding of male adolescent alcohol-related problem behaviour.
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| 29. |
- Nilsson, Kent W, et al.
(författare)
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Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology.
- 2009
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 116:3, s. 363-370
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate possible interactions between the gene coding for activating protein-2 beta (AP-2 beta) and psychosocial factors to predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old adolescents from the county of Västmanland, Sweden, were asked to complete a questionnaire, interviewed about psychosocial risk factors, and genotyped with regard to the transcription factor AP-2 beta intron 2 polymorphism. AP-2 beta genotype interacted significantly both with type of housing and parental separation to predict depressive symptoms. Individuals who were homozygous for the short AP-2 beta allele displayed higher depression scores when psychosocial adversity was taken into account. Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments.
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| 30. |
- Nordquist, Niklas, et al.
(författare)
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Monoallelic expression of MAO-A in skin fibroblasts
- 2007
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:6, s. 713-716
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Tidskriftsartikel (refereegranskat)abstract
- X chromosome inactivation in mammalian females occurs early in embryonic development and renders most genes on the inactive X chromosome transcriptionally silenced. As a consequence, females will display an X chromosomal parent-of-origin mosaicism with regard to which parental allele that is expressed. Some genes however, escape inactivation and will therefore be expressed from both alleles. In this study we have investigated if the X-linked MAO-A gene have bi- or mono-allelic expression. This information would indicate whether or not MAO-A gene dosage could potentially explain the observed gender differences that show functional connections to the serotonin system, such as aggression and impulsiveness. To investigate the X inactivation status of MAO-A we have used primary clonal cell cultures, on which allelic expression was assessed with RFLP analysis. Our results show that the MAO-A gene has mono-allelic expression in these cells. This could have important implications for understanding traits that display gender differences.
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| 31. |
- Nordquist, Niklas, et al.
(författare)
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Monoallelic expression of MAOA in skin fibroblasts
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 348:2, s. 763-767
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Tidskriftsartikel (refereegranskat)abstract
- X chromosome inactivation in mammalian females occurs early in embryonic development and renders most genes on the inactive X chromosome transcriptionally silenced. As a consequence, females will display an X chromosomal parent-of-origin mosaiscism with regard to which parental allele that is expressed. Some genes, however, escape inactivation and will therefore be expressed from both alleles. In this study, we have investigated if the X-linked MAO-A gene has bi- or mono-allelic expression. This information would indicate whether or not MAO-A gene dosage could potentially explain the observed gender differences that show functional connections to the serotonin system, such as aggression, and impulsiveness. To investigate the X inactivation status of MAO-A we have used primary clonal cell cultures, on which allelic expression was assessed with RFLP analysis. Our results show that the MAO-A gene has mono-allelic expression in these cells. This could have important implications for understanding traits that display gender differences.
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| 32. |
- Nordquist, Niklas, et al.
(författare)
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The Transcription Factor TFAP2B Is Associated With Insulin Resistance and Adiposity in Healthy Adolescents
- 2009
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 17:9, s. 1762-1767
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and central adiposity are strong risk indicators for type 2 diabetes and coronary heart disease. An important role for adipose tissue in the etiology and progression of these conditions has recently become more evident. A transcription factor, TFAP2B, has been shown to participate in the regulation of adipocyte metabolism, by facilitating glucose uptake and lipid accumulation, while simultaneously reducing insulin sensitivity, and recently a direct function for TFAP2B as an inhibitor of adiponectin expression was observed. In this study, we have investigated how insulin resistance, plasma adiponectin, and central adiposity, in a normal population of adolescents, are affected by genetic variability in TFAP2B. Our results show that both insulin sensitivity, as measured from levels of fasting glucose and insulin, and central adiposity, estimated by subscapular skinfold thickness, were significantly associated to genetic variability in TFAP2B. This association was restricted to males only, where carriers of the 4-repeat allele of intron 2 had higher insulin sensitivity and lower subscapular skinfold thickness. Levels of adiponectin did not show any association to the TFAP2B polymorphism, but was negatively correlated to central adiposity in females. These results suggest that reduction of TFAP2B expression could have a protective effect against future risk of complications associated with decreased insulin sensitivity and central adiposity, such as type 2 diabetes and coronary heart disease.
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| 33. |
- Nordquist, Niklas, et al.
(författare)
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Transcription factor AP2 beta involved in severe female alcoholism
- 2009
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1305:Supplement 11, s. S20-S26
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to alcoholism and antisocial behavior exhibits an evident link to monoaminergic neurotransmission. The serotonin system in particular, which is associated with regulation of mood and behavior, has an influence on personality characters that are firmly connected to risk of developing alcoholism and antisocial behavior, such as impulsiveness, and aggression. The transcription factor TFAP2b has repeatedly been shown to be involved in monoaminergic transmission, likely due to a regulatory effect on genes that are fundamental to this system, e.g. monoamine oxidase type A, and the serotonin transporter. Recent research has identified a functional polymorphism in the gene encoding TFAP2B that regulates its level of expression. In the present study we have compared a sample of female alcoholics (n = 107), sentenced to institutional care for their severe addiction, contrasted against a control sample of adolescent females (n = 875). The results showed that parental alcohol misuse was significantly more common among the alcoholic females, and also that parental alcohol misuse was associated with a reduction in age of alcohol debut. We also addressed the question of whether a functional TFAP2b polymorphism was associated with alcoholism. Results showed that the high-functioning allele was significantly more common among the female alcoholics, compared to the non-alcoholic controls. Furthermore, the results also indicated that psychosocial factors, in terms of parental alcohol misuse, depression or psychiatric disorder, had an influence on the association. It was observed that the genetic association was restricted to the subset of cases that had not experienced these negative psychosocial factors.
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| 34. |
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| 35. |
- Oreland, Lars, et al.
(författare)
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Monoamine oxidases : activities, genotypes and the shaping of behaviour
- 2007
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Ingår i: Journal of neural transmission. - Uppsala Univ, Dept Neurosci, Uppsala, Sweden. Uppsala Univ, Ctr Clin Res Vasteras, Uppsala, Sweden. : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:6, s. 817-822
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Tidskriftsartikel (refereegranskat)abstract
- The importance of an interaction between environment and biological factors for the expression for a particular behaviour is illustrated by results from a series of adolescents in which effects of platelet MAO activity and psychosocial environment on criminality was investigated. In a favourable environment platelet MAO-B activity was not associated with criminality, while a very strong association was found in adolescents from a bad psychosocial environment. Essentially similar findings were obtained when a MAO-A promoter polymorphism was analysed instead of platelet MAO-B activity. In boys, presence of the low functioning allele seemed to be protective against criminal activity in combination with a good environment, while it predisposed for criminality in a bad psycho-social environment. In girls, instead, homozygosity for the high activity MAO-A allele interacted with environment to predict criminality. Possible mechanisms underlying the role of monoamine oxidases for behaviour are discussed.
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| 36. |
- Paaver, Marika, et al.
(författare)
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Platelet MAO activity and the 5-HTT gene promoter polymorphism are associated with impulsivity and cognitive style in visual information processing
- 2007
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 194:4, s. 545-554
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Tidskriftsartikel (refereegranskat)abstract
- Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning.The effect of the two markers for serotonin system efficiency on performance in a visual comparison task (VCT) and self-reported impulsiveness (Barratt Impulsiveness Scale, BIS-11) were investigated in healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study. Possible confounding effect of general cognitive abilities on the performance in VCT was controlled for.Low platelet MAO activity and carrying of the S allele of 5-HTTLPR were both associated with higher error-rate and more impulsive performance in VCT. Platelet MAO activity and 5-HTTLPR S allele had a significant interactive effect on self-reported impulsivity (BIS-11). The effect of platelet MAO activity on both self-reported and performance impulsivity was significant only in the S allele carriers. The effect of 5-HTTLPR S allele on impulsive performance remained significant after controlling for general cognitive abilities.The two markers of lower serotonergic capacity, 5-HTTLPR S allele and low platelet MAO activity, have a similar and partly synergistic influence on self-reported as well as performance measures of impulsivity.
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| 37. |
- Paaver, Marika, et al.
(författare)
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The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls
- 2008
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 32:5, s. 1263-1268
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Forskningsöversikt (refereegranskat)abstract
- The short (S) allele of the 5-HTT gene promoter region polymorphism (5-HTTLPR), in combination with adverse environmental influence, leads to higher likelihood of depression. Impulsivity has been related to low serotonin turnover, poor regulation of affect, and problems in the family, including child maltreatment. The current study explored the effect of the 5-HTTLPR polymorphism in the serotonin transporter gene and adverse family environment on impulsivity in adolescents. Healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study (n=483) filled the Adaptive and Maladaptive Impulsivity Scale (AMIS), Barratt Impulsiveness Scale (BIS-11), a scale measuring family relations, and were genotyped. While genotype alone was not associated with thoughtlessness, BIS-11 impulsiveness, fast decision-making or excitement seeking, 5-HTTLPR S allele carriers, however, had higher scores of disinhibition. In girls carrying the S allele, scores of thoughtlessness and disinhibition depended on family relations, being higher with less warmth in the family. Adverse family relations had no effect on impulsivity in girls with LL genotype. In boys, the effects of family relations on maladaptive impulsivity did not depend on genotype. However, the S allele and high maltreatment in the family both independently increased disinhibition and the BIS-11 score in boys. Family environment and the 5-HTTLPR genotype had no interactive effect on excitement seeking or fast decision-making. In summary, carrying the S allele may lead to high maladaptive impulsivity due to higher sensitivity to environmental adversity, which is more significantly expressed in girls.
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| 38. |
- Ruchkin, Vladislav V, et al.
(författare)
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Platelet MAO-B, personality, and psychopathology
- 2005
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Ingår i: Journal of Abnormal Psychology. - 0021-843X .- 1939-1846. ; 114:3, s. 477-482
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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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| 39. |
- Sakurai, Eiko, et al.
(författare)
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Evidence for the presence of histamine uptake into the synaptosomes of rat brain
- 2006
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Ingår i: Pharmacology. - : S. Karger AG. - 0031-7012 .- 1423-0313. ; 78:2, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Histamine has many physiological roles in the brain and periphery. Neuronal histamine is metabolized almost exclusively by histamine N-methyltransferase. Although several neurotransmitter systems such as dopamine and 5-hydroxytryptamine have their specific reuptake system in their neurons and glial cells, a specific histamine reuptake system into the corresponding nerve terminals or glial cells has not yet been clearly elucidated. We characterized the uptake of histamine into the P2 fractions of rat brain homogenized in 0.32 mol/l sucrose using in vitro uptake techniques. [3H]histamine uptake increased with the increment of added protein amount and elapsed time. [3H]histamine uptake was also temperature-dependent. The uptake of [3H]histamine into the P2 fractions occurs by two saturable processes, a high-affinity and a low-affinity, characterized by K(m) values of 0.16 and 1.2 micromol/l, respectively. Na(+), Cl(-) and HCO(3)(-) ions were essential for the uptake of histamine in P2 fractions. [3H]histamine uptake was inhibited in the presence of several tricyclic antidepressants. In accordance with this, the endogenous release of histamine from brain slices evoked by 100 mmol/l K(+) was augmented in the presence of 20 micromol/l imipramine. These results further support the existence of a specific histamine uptake system in the brain, although the precise molecular entities have not been identified until now.
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| 40. |
- Sjöberg, Rickard L., et al.
(författare)
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Adolescent girls and criminal activity : Role of MAOA-LPR genotype and psychosocial factors
- 2007
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Ingår i: American Journal of Medical Genetics Part B. - Uppsala Univ, Cent Hosp Vasteras 1, Clin Res Ctr, S-72189 Vasteras, Sweden. Uppsala Univ, Dept Neurosci, Pharmacol Unit, S-75105 Uppsala, Sweden. : Wiley. - 1552-4841 .- 1552-485X. ; 144:2, s. 159-164
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings among boys show that interactions between a polymorphism in the monoamine oxidase A gene promoter region (MAOA-LPR) and psychosocial factors predict criminal activity. The objective of this study was to investigate whether this finding could be extended to adolescent girls. One hundred nineteen female adolescents were recruited among respondents to a cross-sectional study of the total population of 16- and 19-year old girls. These girls constituted a randomly selected sub-sample from groups representing different degrees of risk behavior. The subjects filled in a questionnaire and were interviewed and genotyped with regard to MAOA-LPR. The results indicate that the long, (4-repeat) allele confer an increased risk for criminal behavior in the presence of psychosocial risk. Among girls without social risk, MAOA-LPR genotype was of no importance for criminal behavior. The present results suggest that previous observations on adolescent males, which demonstrate that the short MAOA-LPR genotype and psychosocial adversity interact to predict criminal activity, may not be applicable to females.
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| 41. |
- Sjöberg, Rickard L, et al.
(författare)
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Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene
- 2006
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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
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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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| 42. |
- Takahashi, Kazuya, et al.
(författare)
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Absence of tissue-bound semicarbazide-sensitive amine oxidase activity in carp tissues
- 2007
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Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 80:12, s. 1094-1099
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported that carp (Cyprinus carpio) tissue mitochondria contain a novel form of monoamine oxidase (MAO), which belongs neither to MAO-A nor to MAO-B of the mammalian enzyme. This conclusion results from the findings that the carp MAO was equally sensitive to a selective MAO-A inhibitor clorgyline and to the MAO-B selective inhibitor l-deprenyl, when tyramine, a substrate for both forms, serotonin or beta-phenylethylamine, a substrate for either A or B-form of mammalian MAO, was used. In the present study, we tried to detect another amine oxidase, termed tissue-bound semicarbazide-sensitive amine oxidase (SSAO), activity in carp tissues. As definition of SSAO was used, such as insensitivity to inhibition of the kynuramine oxidizing activity by an MAO inhibitor pargyline and high sensitivity to the SSAO inhibitor semicarbazide. The results indicated that the oxidizing activity was selectively and almost completely inhibited by 0.1 mM pargyline alone or a combination of 0.1 mM pargyline plus 0.1 mM semicarbazide, but not by 0.1 mM semicarbazide alone. We also tried to detect any SSAO activity by changing experimental conditions, such as lower incubation temperature, higher enzyme protein concentration, a lower substrate concentration and different pH's in the reaction, as the enzyme source. However, still no SSAO activity could be detected in the tissues. These results conclusively indicate that carp tissues so far examined do not contain SSAO activity.
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| 43. |
- Åslund, Cecilia, 1977-
(författare)
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Depression and Antisocial Behaviour in Adolescents : Influence of Social Status, Shaming, and Gene-Environment Interaction
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigated (1) social status and shaming experiences in relation to aggressive behaviour and depression, and (2) gene-environment interactions between two genetic polymorphisms related to the serotonergic system – MAOA-VNTR and 5HTTLPR – and experiences of maltreatment in relation to delinquent behaviour and depression among adolescents. The four included studies are based on questionnaire data from the Survey of Adolescent Life in Vestmanland 2006 (SALVe-2006). A total of 5396 students in 9th (15-16 years old) grade of elementary school and 2nd (17-18 years old) grade of high school comprised the target population. The students in 2nd grade of high school also provided a saliva sample for gene extraction. There were strong associations between shaming experiences and both aggressive behaviour and depression. In addition, individuals who reported many shaming experiences and had either low or high social status had increased risks of physical aggression or depression, whereas medium social status seemed to have a protective effect. Gene-environment interactions were found between experiences of maltreatment and the MAOA-VNTR in relation to delinquent behaviour. Moreover, the direction of the gene-environment interaction differed depending on sex: boys with the short (S) variant of the MAOA-VNTR, in contrast to girls with the long (LL) variant, had the highest risk of delinquency in combination with maltreatment. Gene-environment interactions were also found between experiences of maltreatment and the 5HTTLPR in relation to depression among girls. The girls that were homozygous for the S allele (SS) had the highest risk of depression in combination with maltreatment. Among boys however, no gene-environment interaction was found between the 5HTTLPR and maltreatment in relation to depression. In conclusion, it is important to consider both genetic effects, and psychosocial factors such as social status, shaming experiences, and experiences of maltreatment when investigating different aspects of health and behaviour among adolescents.
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- Åslund, Cecilia, 1977-, et al.
(författare)
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Impact of the interaction between the 5HTTLPR polymorphism and maltreatment on adolescent depression. : A population-based study
- 2009
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 39:5, s. 524-531
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin plays a central role in mood regulation and the development of depressive disorders. The present study investigated whether a functional polymorphism (5HTTLPR) of the serotonin transporter gene interacts with maltreatment in the prediction of depression. A cohort of 17-18 year old students (n=1482) anonymously completed the Survey of Adolescent Life and Health in Vestmanland 2006 and gave a saliva sample for DNA extraction. An association between maltreatment and adolescent depression was found independent of sex. When the whole population was analyzed, no main effect of 5HTTLPR in association with depression was found. When separated by sex, a significant main effect and a GxE interaction effect of the SS allele was found among girls. No gene main effect or GxE interaction effect was found among boys. The present study confirms previous findings of sex differences in interaction effects between the 5HTTLPR polymorphism and maltreatment in the prediction of adolescent depression.
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