| 1. |
- de Frias, Cindy M, et al.
(author)
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Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.
- 2005
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In: Journal of cognitive neuroscience. - Cambridge : MIT Press - Journals. - 0898-929X .- 1530-8898. ; 17:7, s. 1018-25
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Journal article (peer-reviewed)abstract
- The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val158Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.
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| 2. |
- de Frias, Cindy M, et al.
(author)
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COMT gene polymorphism is associated with declarative memory in adulthood and old age.
- 2004
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In: Behavior genetics. - New York : Kluwer Academic Publishers. - 0001-8244 .- 1573-3297. ; 34:5, s. 533-9
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Journal article (peer-reviewed)abstract
- Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.
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| 3. |
- Sundblad-Elverfors, Charlotta, 1959, et al.
(author)
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Effects of the androgen antagonist flutamide and the serotonin reuptake inhibitor citalopram in bulimia nervosa: a placebo-controlled pilot study.
- 2005
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In: Journal of clinical psychopharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0271-0749. ; 25:1, s. 85-8
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Journal article (peer-reviewed)abstract
- Prompted by previous studies suggesting that bulimia nervosa in women may be associated with elevated serum levels of testosterone, we have evaluated the possible effect of androgen antagonism in this condition. To this end, women meeting the DSM-IV criteria of bulimia nervosa, purging type, were treated in a one-center study with the androgen receptor antagonist flutamide (n = 9), the serotonin reuptake inhibitor citalopram (n = 15), flutamide plus citalopram (n = 10), or placebo (n = 12) for 3 months using a double-blind design. Self-rated global assessment of symptom intensity suggests all active treatments to be superior to placebo. The reduction in binge eating compared with baseline was statistically significant in both groups given flutamide but not in the groups given citalopram only or placebo. A moderate and reversible increase in serum transaminase levels led to discontinuation in two subjects in the flutamide group. It is concluded that blockade of androgen receptors may reduce some of the symptoms of bulimia nervosa in women.
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| 4. |
- Alexanderson, Camilla, 1978, et al.
(author)
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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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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 35
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Journal article (peer-reviewed)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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| 5. |
- Alexanderson, Camilla, 1978, et al.
(author)
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Postnatal testosterone exposure results in insulin resistance, enlarged mesenteric adipocytes, and an atherogenic lipid profile in adult female rats: comparisons with estradiol and dihydrotestosterone.
- 2007
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In: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:11, s. 5369-76
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Journal article (peer-reviewed)abstract
- Postnatal events contribute to features of the metabolic syndrome in adulthood. In this study, postnatally administered testosterone reduced insulin sensitivity and increased the mesenteric fat depot, the size of mesenteric adipocytes, serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and the atherogenic index in adult female rats. To assess the involvement of estrogen and androgen receptors in these programming effects, we compared testosterone-exposed rats to rats exposed to estradiol or dihydrotestosterone (DHT). Estradiol-treated rats had lower insulin sensitivity than testosterone-treated rats and, like those rats, had enlarged mesenteric adipocytes and increased triglyceride levels. DHT also reduced insulin sensitivity but did not mimic the other metabolic effects of testosterone. All treated rats were probably anovulatory, but only those treated with testosterone had reduced testosterone levels. This study confirms our previous finding that postnatal administration of testosterone reduces insulin sensitivity in adult female rats and shows that this effect is accompanied by unfavorable changes in mesenteric fat tissue and in serum lipid levels. The findings in the estradiol and DHT groups suggest that estrogen receptors exert stronger metabolic programming effects than androgen receptors. Thus, insults such as sex hormone exposure in early life may have long-lasting effects, thereby creating a predisposition to disturbances in insulin sensitivity, adipose tissue, and lipid profile in adulthood.
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| 6. |
- Annerbrink, Kristina, 1974, et al.
(author)
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Catechol O-methyltransferase val158-met polymorphism is associated with abdominal obesity and blood pressure in men.
- 2008
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In: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 57:5, s. 708-711
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Journal article (peer-reviewed)abstract
- Catechol O-methyltransferase (COMT) degrades catecholamines and estrogens, both of which are of known importance for cardiovascular risk factors such as obesity and hypertension. The gene coding for COMT contains a val158-met polymorphism that exerts a considerable influence on enzymatic activity. We hypothesized that this polymorphism might influence risk factors for cardiovascular disease. Deoxyribonucleic acid samples and data regarding blood pressure and anthropometry were collected from 240 Swedish men, all 51 years old. Subjects homozygous for the low-activity allele (met) displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter as compared with heterozygous subjects, who in turn displayed higher blood pressure, heart rate, waist-to-hip ratio, and abdominal sagittal diameter than subjects homozygous for the high-activity allele (val). All measured variables were significantly correlated; however, the associations between COMT val158-met and cardiovascular variables, and the association between COMT val158-met and anthropometry, respectively, were partly independent of each other, as revealed by multiple linear regression.
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| 7. |
- Bah Rösman, Jessica, 1975, et al.
(author)
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Serotonin transporter gene polymorphisms: Effect on serotonin transporter availability in the brain of suicide attempters
- 2008
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In: Psychiatry Research: Neuroimaging. - : Elsevier BV. - 0925-4927 .- 0165-1781. ; 162:3, s. 221-229
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Journal article (peer-reviewed)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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| 8. |
- Bergman, Olle, 1978, et al.
(author)
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PITX3 polymorphism is associated with early onset Parkinson's disease.
- 2010
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 31:1, s. 114-117
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Journal article (peer-reviewed)abstract
- PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p=0.002) or to PD patients with late onset (p=0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated.
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| 9. |
- Damberg, Mattias, et al.
(author)
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Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
- 2005
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In: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
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Journal article (peer-reviewed)abstract
- It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2beta in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2beta in regulatory regions, suggesting an involvement of AP-2beta in these systems. The gene encoding AP-2beta is located on chromosome 6p12-p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2beta genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2beta correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2beta genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2beta genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2beta genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2beta genotype in women with PMDD. Hence, these results should be considered preliminary until replicated.
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| 10. |
- Ekman, Agneta, 1961, et al.
(author)
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Low density and high affinity of platelet [3H]paroxetine binding in women with bulimia nervosa.
- 2006
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In: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 142:2-3, s. 219-23
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Journal article (peer-reviewed)abstract
- Impaired serotonin transmission has been suggested to be implicated in the pathophysiology of bulimia nervosa. As an indirect measure of brain serotonergic activity, the binding of tritiated ligands to platelet serotonin transporters has been studied in bulimia nervosa as well as in other putatively serotonin-related psychiatric disorders. In this study, the density and affinity of platelet serotonin transporters were assessed in 20 women meeting the DSM-IV criteria for bulimia nervosa and in 14 controls without previous or ongoing eating disorder using [(3)H]paroxetine as a ligand. In comparison to controls, women with bulimia nervosa had a significantly reduced number of platelet binding sites (B(max) = 721 +/- 313 vs. 1145 +/- 293 fmol/mg protein) and an increase in the affinity for the ligand demonstrated by a lower dissociaton constant (K(d) = 33 +/- 10 vs. 44 +/- 10 pM). A significant correlation between B(max) and K(d) values was found in patients but not in controls. Our results support the notion that bulimia nervosa is associated with a reduction in platelet serotonin transporter density. In addition, our study is the first to report that this reduced transporter density in women with bulimia nervosa is accompanied by an increase in the affinity of the transporter for the ligand.
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