| 1. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Sex steroid-related genes and male-to-female transsexualism
- 2005
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Ingår i: Psychoneuroendocrinology. - Oxford : Pergamon Press. - 0306-4530 .- 1873-3360. ; 59:5, s. 412-412
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Tidskriftsartikel (refereegranskat)abstract
- Transsexualism is characterised by Lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and-after aromatase-catalyzed conversion to estradiol-via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ER beta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy mate controls. Transsexuals differed from controls with respect to the mean Length of the ER repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.
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| 2. |
- Westberg, Lars, 1973, et al.
(författare)
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Influence of androgen receptor repeat polymorphisms on personality traits in men
- 2009
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Ingår i: Journal of Psychiatry and Neuroscience. - 1488-2434 .- 1180-4882. ; 34:3, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Background Testosterone has been attributed importance for various aspects of behaviour. The aim of our study was to investigate the potential influence of 2 functional polymorphisms in the amino terminal of the androgen receptor on personality traits in men. Methods We assessed and genotyped 141 men born in 1944 recruited from the general population. We used 2 different instruments: the Karolinska Scales of Personality and the Temperament and Character Inventory. For replication, we similarly assessed 63 men recruited from a forensic psychiatry study group. Results In the population-recruited sample, the lengths of the androgen receptor repeats were associated with neuroticism, extraversion and self-transcendence. The association with extraversion was replicated in the independent sample. Limitations Our 2 samples differed in size; sample 1 was of moderate size and sample 2 was small. In addition, the homogeneity of sample 1 probably enhanced our ability to detect significant associations between genotype and phenotype. Conclusion Our results suggest that the repeat polymorphisms in the androgen receptor gene may influence personality traits in men.
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| 3. |
- Alexanderson, Camilla, 1978, et al.
(författare)
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Influence of having a male twin on body mass index and risk for dyslipidemia in middle-aged and old women.
- 2011
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background:Animal experiments suggest that exposure to elevated levels of androgens during development by means of so-called hormonal programming causes metabolic aberrations at adulthood. An indirect strategy to address the possible importance of such an influence also in humans would be to study female dizygotic twins, presuming that those with a twin brother-due to diffusion of testosterone-have been exposed to higher androgen levels prenatally.Design:We have compared 8409 women with a male twin with 9166 women with a dizygotic female twin with respect to self-reported indices of anthropometry and metabolic aberrations at age 42 or older.Results:Body mass index (BMI), body weight and rate of dyslipidemia were moderately, but significantly, higher in women from opposite-sexed (OS) twin pairs; splitting for age revealed this difference to be present in those 60 years of age only.Conclusion:The results (i) support the notion that comparisons of women with a twin brother with women from same-sexed twin pairs may be used to shed light on possible long-term effects of interindividual variations in early androgen exposure, and (ii) suggest that the effects of early androgen exposure on metabolism previously observed in animal experiments are of relevance also for humans.International Journal of Obesity advance online publication, 8 March 2011; doi:10.1038/ijo.2011.18.
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| 4. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
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Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weight.
- 2010
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495. ; 59:8, s. 1156-1163
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Tidskriftsartikel (refereegranskat)abstract
- Receptors of the 5-HT2C subtype are of importance for the influence of serotonin on food intake, and 2 single nucleotide polymorphisms in this gene (HTR2C)-Cys23Ser (rs6318) and -759C>T (rs3813929)-have been reported to be associated with weight and/or antipsychotic-induced weight gain. The present study aimed to replicate these associations; in addition, the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) was assessed. The polymorphisms were genotyped in subjects recruited from the normal population (n = 510), and possible associations between genotype and body mass index (BMI) were assessed. The Ser23 allele was more common in underweight subjects (BMI <20) than in normal- and overweight (BMI >/=20) subjects (P = .006). The T allele of the -759C/T polymorphism was less common in the overweight group (BMI >/=25) (P = .007). Homozygosity for the short allele of 5-HTTLPR was more frequent in underweight subjects (P = .015). Our results are in agreement with previous studies, suggesting polymorphisms in HTR2C to be associated with body weight, particularly in women; and they also suggest that 5-HTTLPR may influence this phenotype. Further studies on the importance of the investigated genes for eating disorders and drug-induced weight gain are warranted.
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| 5. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
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Serotonin transporter gene polymorphisms: Effect on serotonin transporter availability in the brain of suicide attempters
- 2008
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Ingår i: Psychiatry Research: Neuroimaging. - : Elsevier BV. - 0925-4927 .- 0165-1781. ; 162:3, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using I-123-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.
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| 6. |
- Bergman, Olle, 1978, et al.
(författare)
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Association between amygdala reactivity and a dopamine transporter gene polymorphism.
- 2014
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.
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| 7. |
- 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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| 8. |
- 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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| 9. |
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| 10. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men
- 2009
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:5, s. 477-485
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Tidskriftsartikel (refereegranskat)abstract
- Background: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). Methods: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [C-11]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [C-11]WAY-100635. Results: Several single nucleotide polymorphisms were associated with [C-11]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [C-11]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with I-123-beta-CIT as ligand. Conclusions: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.
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