| 1. |
- Culverhouse, R. C., et al.
(författare)
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Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
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| 2. |
- 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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| 3. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Cognitive impairment in patients with stress-related exhaustion
- 2013
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Ingår i: Stress-the International Journal on the Biology of Stress. - : Informa UK Limited. - 1025-3890 .- 1607-8888. ; 16:2, s. 181-190
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Tidskriftsartikel (refereegranskat)abstract
- Patients who seek medical care for stress-related mental health problems frequently report cognitive impairments as the most pronounced symptom. The purpose of the present study was to compare cognitive function in patients with stress-related exhaustion with that in healthy controls, using a comprehensive battery of cognitive tests. We also explored whether neuropsychological findings were related to severity of illness measured using the Shirom–Melamed burnout questionnaire and hospital anxiety and depression scale. Thirty-three patients (15 males) and 37 healthy controls (11 males), mean age 46 years [standard deviation (SD) 3.9] and 47 years (SD 4.3), respectively, were included in the final analysis. Five cognitive domains were assessed: (1) speed, attention and working memory, (2) learning and episodic memory, (3) executive functions, (4) visuospatial functions and (5) language. The most pronounced difference between patients and controls was seen on executive function, when tested with a multidimensional test, including aspects of speed, control and working memory. The patients also performed poorer on Digit span, measuring attention span and working memory as well as on learning and episodic memory, when measured as delayed recall and the difference between immediate and delayed recall. Delayed recall was the only test that was significantly related to severity of burnout symptoms among the patients. This could reflect poor cognitive sustainability in the patients with the highest burnout scores, as this particular test was the last one performed during the test session. This study clearly shows that cognitive impairment should be considered when evaluating and treating patients who seek medical care for stress-related exhaustion.
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| 4. |
- Lindner, Philip, et al.
(författare)
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Amygdala-orbitofrontal structural and functional connectivity in females with anxiety disorders, with and without a history of conduct disorder
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are characterized by hyper-sensitivity to threat, and reduced structural and functional connectivity between the amygdala and orbitofrontal cortex (OFC). Previous studies of CD have not taken account of ADs nor directly compared connectivity in the two disorders. We examined three groups of young women: 23 presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with neither disorder (ND). Participants completed clinical assessments and diffusion-weighted and resting-state functional MRI scans. The uncinate fasciculus was reconstructed using tractography and manual dissection, and structural measures extracted. Correlations of resting-state activity between amygdala and OFC seeds were computed. The CD + AD and AD groups showed similarly reduced structural integrity of the left uncinate compared to ND, even after adjusting for IQ, psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was associated with harm avoidance traits among AD-only women, and with the interaction of poor anger control and anxiety symptoms among CD + AD women. Groups did not differ in functional connectivity. Reduced uncinate integrity observed in CD + AD and AD-only women may reflect deficient emotion regulation in response to threat, common to both disorders, while other neural mechanisms determine the behavioral response.
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| 5. |
- Hultman, Cathrine, et al.
(författare)
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Exploring decision-making strategies in the Iowa gambling task and rat gambling task
- 2022
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media S.A.. - 1662-5153 .- 1662-5153. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Decision-making requires that individuals perceive the probabilities and risks associated with different options. Experimental human and animal laboratory testing provide complimentary insights on the psychobiological underpinnings of decision-making. The Iowa gambling task (IGT) is a widely used instrument that assesses decision-making under uncertainty and risk. In the task participants are faced with a choice conflict between cards with varying monetary reinforcer/loss contingencies. The rat gambling task (rGT) is a pre-clinical version using palatable reinforcers as wins and timeouts mimicking losses. However, interspecies studies elaborating on human and rat behavior in these tasks are lacking. This study explores decision-making strategies among young adults (N = 270) performing a computerized version of the IGT, and adult outbred male Lister Hooded rats (N = 72) performing the rGT. Both group and individual data were explored by normative scoring approaches and subgroup formations based on individual choices were investigated. Overall results showed that most humans and rats learned to favor the advantageous choices, but to a widely different extent. Human performance was characterized by both exploration and learning as the task progressed, while rats showed relatively consistent pronounced preferences for the advantageous choices throughout the task. Nevertheless, humans and rats showed similar variability in individual choice preferences during end performance. Procedural differences impacting on the performance in both tasks and their potential to study different aspects of decision-making are discussed. This is a first attempt to increase the understanding of similarities and differences regarding decision-making processes in the IGT and rGT from an explorative perspective.
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| 6. |
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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