| 1. |
- Comasco, Erika, 1982-, et al.
(author)
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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
- 2017
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In: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
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Journal article (peer-reviewed)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.
(author)
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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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In: Child Psychiatry and Human Development. - : SPRINGER. - 0009-398X .- 1573-3327. ; 48:4, s. 584-596
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Journal article (peer-reviewed)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. |
- Comasco, Erika, 1982-
(author)
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Alcohol Consumption among Adolescents : Psychosocial and Genetic influences
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The present thesis is based on four studies focusing on alcohol consumption among Swedish adolescents, and therewith related psychosocial and genetic factors. One main objective was to study the reasons for drinking alcohol among different population - representative samples of adolescents in order to identify motives for drinking. Relationships between these drinking motives, alcohol consumption, and alcohol - related problems were also investigated. Three motives emerged from this study: social - enhancement, coping and dominance. The association with alcohol consumption and alcohol - related problems was positive for social - enhancement and coping motives, but negative for the dominance motive. A significant heritability of alcohol use disorders has been demonstrated by family, adoption and twin studies. Environmental influences have also been acknowledged to play an important role in the development of alcohol use disorders. Moreover, the interaction between genetic and environmental factors is likely to influence the risk - resilience for alcohol use disorders. In view of this knowledge, plausible candidate polymorphisms were considered in gene - environment interaction models. An effect of the genetic polymorphisms was only present when a G x E model was considered. A genetic variant of the clock gene Period2, in an interaction with sleep problems, was studied in relation to alcohol consumption among adolescents. High alcohol consumption was associated with the AA genotype of the PER2 SNP10870 polymorphism, in an interaction with several and frequent sleep problems, among adolescent boys. A genetic variant in the opioid µ receptor 1 gene, in an interaction with alcohol consumption, was studied in relation to depressive symptoms. Depressive symptoms were predicted by the G allele of the OPRM1 A118G polymorphism, in an interaction with high alcohol consumption, among adolescent girls. Additionally, the PER2 SNP10870 and the OPRM1 A118G polymorphisms were studied in a sample of severely alcoholic females. Furthermore, alcohol consumption was assessed by using different instruments, such as biomarkers and surveys. Comparisons were carried out to identify the most suitable method to assess alcohol consumption among adolescents. Questionnaire and interview seemed more suitable tools than biomarkers in this regard.The results eventually support the importance of psychosocial and genetic influences, and their interaction effect on alcohol consumption among adolescents.
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| 4. |
- Comasco, Erika, 1982-, et al.
(author)
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Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure
- 2018
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In: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 222:1
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Journal article (peer-reviewed)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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| 5. |
- Joost, Urmeli, et al.
(author)
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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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In: International Journal of Obesity. - : NATURE PUBLISHING GROUP. - 0307-0565 .- 1476-5497. ; 43:10, s. 2095-2106
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Journal article (peer-reviewed)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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| 6. |
- Nilsson, Kent W., et al.
(author)
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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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In: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 125:11, s. 1601-1626
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Research review (peer-reviewed)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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| 7. |
- Oreland, Lars, et al.
(author)
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Personality as an intermediate phenotype for genetic dissection of alcohol use disorder.
- 2018
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In: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 125:1, s. 107-130
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Research review (peer-reviewed)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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| 8. |
- Rydman, Eric, et al.
(author)
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COMT genotype and non-recovery after a whiplash injury in a Northern European population
- 2017
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 18
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Journal article (peer-reviewed)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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