| 1. |
- Comasco, Erika, 1982-, et al.
(författare)
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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
- 2017
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Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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| 2. |
- Agnafors, Sara, et al.
(författare)
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A Biopsychosocial Approach to Risk and Resilience on Behavior in Children Followed from Birth to Age 12
- 2017
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Ingår i: Child Psychiatry and Human Development. - : SPRINGER. - 0009-398X .- 1573-3327. ; 48:4, s. 584-596
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Tidskriftsartikel (refereegranskat)abstract
- An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on preadolescence behavior. Data from 889 children and mothers from a birth cohort were used. An adversity score was created by combining maternal symptoms of depression, psychosocial risk and childrens experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament, social functioning, and maternal sense of coherence. The l/ l genotype of the serotonin transporter linked polymorphic region was associated with lower internalizing scores, but not mainly related to the level of adversity. An easy temperament was associated with resilience for children exposed to high adversity. Social functioning was found to be promotive independent of the risk level. The results support a multiple-level model of resilience indicating effects, though small, of both biological and psychosocial factors.
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| 3. |
- Agnafors, Sara, et al.
(författare)
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A biopsychosocial approach to risk and resilience on behavior in children followed from birth to age twelve
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience in the context of child behavior. Biological factors are seldom considered in psychosocial models of resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on behavior at preadolescence. Data from 889 children and their mothers were used. A cumulative adversity score was created by combining maternal symptoms of depression, psychosocial risk and children’s experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament and social functioning, and maternal sense of coherence. Results show that the l/l genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) was associated with lower internalizing scores, especially for children exposed to low adversity. An easy temperament was associated with resilient outcomes for children exposed to high adversity. Child social functioning was found to be more of a general resource variable buffering risk in both high and low adversity groups. The results support a multiple level model of resilience indicating effects, though small, of both biological and psychosocial factors. The present findings call for both preventive actions and further studies on biopsychosocial models in resilience research.
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| 4. |
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| 5. |
- Agnafors, Sara, et al.
(författare)
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Early predictors of behavioural problems in pre-schoolers : a longitudinal study of constitutional and environmental main and interaction effects
- 2016
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431 .- 1471-2431. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age 3, using a comparably large, representative, population-based sample. Methods: A total of 1,106 children, and their mothers, were followed from pregnancy to age 3. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms. Results: Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-by-gene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems. Conclusion: This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children.
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| 6. |
- Comasco, Erika, 1982-, et al.
(författare)
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Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure
- 2018
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 222:1
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Tidskriftsartikel (refereegranskat)abstract
- Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified.
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| 7. |
- Harro, Jaanus, et al.
(författare)
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The role of MAO in personality and drug use
- 2016
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Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846 .- 1878-4216. ; 69, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- Monoamine oxidases, both MAO-A and MAO-B, have been implicated in personality traits and complex behaviour, including drug use. Findings supporting the involvement of MAO-A and MAO-B in shaping personality and in the development of strategies of making behavioural choices come from a variety of studies that have examined either prevalence of gene variants in clinical groups or population-derived samples, estimates of enzyme activity in blood or, by positron emission tomography, in the brain and, most recently, measurement of methylation of the gene. Most of the studies converge in associating MAO-A and MAO-B with impulsive, aggressive or antisocial personality traits or behaviours, including alcohol-related problems, and for MAO-A available evidence strongly supports interaction with adverse environmental exposures in childhood. What is known about genotype effects, and on expression and activity of the enzyme in the brain and in blood has not yet been possible to unite into a mechanistic model of the role of monoamine systems, but the reason for this low degree of generalization is likely caused by the cross-sectional nature of investigation that has not incorporated the developmental effects of MAO-s in critical time windows, including the foetal period. The "risk variants" of both MAO-s appear to increase behavioural plasticity, as supportive environments may particularly well enhance the hidden potential of their carriers. Importantly, male and female brain and behaviours have been found very different with regard to MAO x life events interaction. Future studies need to take into consideration these developmental aspects and sex/gender, as well as to specify the role of different types of environmental factors.
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| 8. |
- Isaksson, Johan, et al.
(författare)
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Exploring possible association between D beta H genotype (C1021T), early onset of conduct disorder and psychopathic traits in juvenile delinquents
- 2016
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 266:8, s. 771-773
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Tidskriftsartikel (refereegranskat)abstract
- Early onset of conduct disorder (CD) with callous-unemotional traits has been linked to low levels of dopamine β-hydroxylase (DβH), an enzyme involved in dopamine turnover. The C1021T polymorphism in the DβH gene is a major quantitative-trait locus, regulating the level of DβH. In this study of juvenile delinquents from Northern Russia (n = 180), the polymorphism at -1021 was associated neither with early-onset CD nor with psychopathic traits. Association was found between psychopathic traits and early-onset CD, ADHD and mania.
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| 9. |
- Isaksson, Johan, et al.
(författare)
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Exploring possible association between DβH genotype (C1021T), early onset of conduct disorder and psychopathic traits in juvenile delinquents.
- 2016
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 266:8, s. 771-773
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Tidskriftsartikel (refereegranskat)abstract
- Early onset of conduct disorder (CD) with callous-unemotional traits has been linked to low levels of dopamine β-hydroxylase (DβH), an enzyme involved in dopamine turnover. The C1021T polymorphism in the DβH gene is a major quantitative-trait locus, regulating the level of DβH. In this study of juvenile delinquents from Northern Russia (n = 180), the polymorphism at -1021 was associated neither with early-onset CD nor with psychopathic traits. Association was found between psychopathic traits and early-onset CD, ADHD and mania.
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| 10. |
- Jokinen, Jussi, et al.
(författare)
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Platelet monoamine oxidase activity and interpersonal violence in male suicide attempters
- 2018
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 260, s. 173-176
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Tidskriftsartikel (refereegranskat)abstract
- Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central serotonergic functions, has been shown to correlate with criminal behavior in adolescents that come from an unfavorable psychosocial environment but not in adolescents from good conditions, indicating a link between environment, MAO-B activity and aggressive behavior. The purpose of this study was to examine the association between MAO-B activity and lifetime interpersonal violence in suicide attempters. The study included a total of 28 suicide attempters (18 men and 10 women). Assessments of childhood exposure to and expressed interpersonal violence during childhood and as an adult were carried out with the Karolinska Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2-phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations between platelet MAO-B activity and both exposure scores to interpersonal violence as a child and expressed lifetime interpersonal violence were significant in male suicide attempters (r = -0.61, p = 0.035; r = - 0.84, p = 0.0005), but not in women. Our finding of significant associations between interpersonal violence and low MAO-B activity need to be replicated in other cohorts of suicide attempters.
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| 11. |
- Joost, Urmeli, et al.
(författare)
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Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study
- 2019
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Ingår i: International Journal of Obesity. - : NATURE PUBLISHING GROUP. - 0307-0565 .- 1476-5497. ; 43:10, s. 2095-2106
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Tidskriftsartikel (refereegranskat)abstract
- Background The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age. Methods The sample included both birth cohorts (originally n = 1176) of the longitudinal Estonian Children Personality Behaviour and Health Study. The association between TFAP2B genotype, and anthropometric measurements, glucose metabolism and dietary intake at ages 15, 18 and 25 years was assessed using the linear mixed-effects regression models. Differences in anthropometric measurements, biochemical measures, blood pressure and dietary intake between TFAP2B genotypes at different age, including data of the older cohort at age 33, were assessed by one-way ANOVA. Results Male homozygotes for the TFAP2B 5-repeat allele had significantly higher body weight, body mass index, sum of 5 skinfolds, proportion of body fat, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, fasting insulin and HOMA index. In female subjects, homozygotes for the TFAP2B 5-repeat allele had significantly larger increase in the rate of change per year in body weight, body mass index and hip circumference between years 15 and 25. By age 33, the findings were similar. A decrease in daily energy intake from adolescence to young adulthood was observed. In males, heterozygotes had significantly smaller decrease in the rate of change per year in daily energy intake. Conclusions The association of TFAP2B with the development of obesity and insulin resistance is present throughout adolescence to young adulthood in males. In females the effect of TFAP2B on obesity appears later, in young adulthood. The TFAP2B effect is rather related to differences in metabolism than energy intake.
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| 12. |
- Nilsson, Kent W., et al.
(författare)
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Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour : current and future directions.
- 2018
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 125:11, s. 1601-1626
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Forskningsöversikt (refereegranskat)abstract
- Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene–environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed.
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| 13. |
- Nilsson, Kent W., et al.
(författare)
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Genotypes Do Not Confer Risk For Delinquency ut Rather Alter Susceptibility to Positive and Negative Environmental Factors : Gene-Environment Interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR
- 2015
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Ingår i: International Journal of Neuropsychopharmacology. - : OXFORD UNIV PRESS. - 1461-1457 .- 1469-5111. ; 18:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. Methods: In 2006, as part of the Survey of Adolescent Life in Vastmanland, Sweden, 1 337 high-school students, aged 1718 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. Results: Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met x 5-HTTLPRxMAOA-uVNTR x family conflicts and for BDNF Val66Met x 5-HTTLPRxMAOA-uVNTR x sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met x 5-HTTLPR S x MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. Conclusions: Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.
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| 14. |
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| 15. |
- Oreland, Lars, et al.
(författare)
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Personality as an intermediate phenotype for genetic dissection of alcohol use disorder.
- 2018
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 125:1, s. 107-130
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Forskningsöversikt (refereegranskat)abstract
- Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger's Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD.
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| 16. |
- Rydman, Eric, et al.
(författare)
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COMT genotype and non-recovery after a whiplash injury in a Northern European population
- 2017
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery.Methods: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life.Results: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery.Conclusion: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports.
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