| 1. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
-
Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weight.
- 2010
-
Ingår i: Metabolism. - : Elsevier BV. - 0026-0495. ; 59:8, s. 1156-1163
-
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.
|
|
| 2. |
- Bah Rösman, Jessica, 1975
(författare)
-
Influence of serotonin-related genes on behavior and body weight
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rationale: The neurotransmitter serotonin has been implicated in the regulation of normal behaviors, including food intake, and attributed importance for a variety of common psychiatric conditions, including major depression, suicidal behavior, eating disorders and premenstrual dysphoria. The purpose of these studies was to explore the possible influence of genetic variation in serotonin-related genes on a) body weight, b) binding capacity of the serotonin transporter in the brain of suicide attempters and c) a disorder for which numerous findings suggest serotonin to play a key role, i.e., premenstrual dysphoria. Observations: 1) An amino acid substitution (Cys23Ser) in the gene encoding the serotonin receptor 5-HT2C (HTR2C) was associated with weight loss in teenage girls. 2) Supporting the above-mentioned finding, the Cys23Ser substitution in the HTR2C was associated with low body weight also in a middle-aged female cohort recruited from the general population; in addition, influences on weight of a SNP in the promoter region of HTR2C, as well of a polymorphism, 5-HTTLPR, in the gene encoding the serotonin transporter, SLC6A4, were found. 3) Both the 5-HTTLPR polymorphism and a variable number of tandem repeats (VNTR) in intron 2 (STin2) of SLC6A4 were shown to be associated with binding capacity of the serotonin transporter in brains of suicide attempters. 4) Genes coding for the serotonin receptor subunit 5-HT3B and a transcription factor involved in the development and differentiation of serotonergic neurons, GATA2, were associated with premenstrual dysphoria. Conclusions: Our results add to the growing literature suggesting variations in serotonin-related genes to be of importance for inter-individual differences in behavior.
|
|
| 3. |
- Bah Rösman, Jessica, 1975, et al.
(författare)
-
Serotonin transporter gene polymorphisms: Effect on serotonin transporter availability in the brain of suicide attempters
- 2008
-
Ingår i: Psychiatry Research: Neuroimaging. - : Elsevier BV. - 0925-4927 .- 0165-1781. ; 162:3, s. 221-229
-
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.
|
|
| 4. |
- Borg,, et al.
(författare)
-
Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans.
- 2009
-
Ingår i: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). - 1461-1457. ; 12:6, s. 783-792
-
Tidskriftsartikel (refereegranskat)abstract
- The human serotonin transporter (5-HTT) gene is one of the most extensively studied in psychiatry. A functional polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR) has been associated with several psychiatric disorders as well as anxiety-related personality traits. In search of a mechanistic understanding of the functional implications of 5-HTTLPR, the influence of this polymorphism on regional 5-HT1A receptor density has previously been examined in two positron emission tomography (PET) studies in humans, yielding, however, contradictory results. In the present study, 54 control subjects were examined with [11C]WAY 100635 PET and a battery of cognitive tests. Regional binding potential (BP) of [11C]WAY 100635 to 5-HT1A receptor was calculated for the dorsal raphe nuclei, the hippocampus, the anterior cingulate, the insula, the temporal cortex and the frontal cortex. The influence of 5-HTTLPR genotype on regional 5-HT1A BP and cognitive performance was investigated. No differences in 5-HT1A receptor density between carriers and non-carriers of the S allele were found. Thus, we could not replicate any of the previously reported associations between 5-HTTLPR and 5-HT1A density. There was, however, a highly significant association between 5-HTTLPR genotype and performance in Wisconsin Card Sorting Test; carriers of the S allele had a superior performance compared to the LL carriers. These observations suggest that functional implications of the 5-HTTLPR polymorphism are not likely to be mediated by differences in 5-HT1A expression levels and that other biomarkers must be considered for future investigations at phenotype level.
|
|
| 5. |
- Henningsson, Susanne, 1977, et al.
(författare)
-
Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men
- 2009
-
Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 66:5, s. 477-485
-
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.
|
|
| 6. |
- Jönsson, Erik G, et al.
(författare)
-
Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers.
- 2004
-
Ingår i: BMC psychiatry. - 1471-244X. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D4 receptor (DRD4), and the dopamine beta-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.
|
|
| 7. |
- Westberg, Lars, 1973, et al.
(författare)
-
Association between a polymorphism of the 5-HT2C receptor and weight loss in teenage girls.
- 2002
-
Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - 0893-133X. ; 26:6, s. 789-93
-
Tidskriftsartikel (refereegranskat)abstract
- Receptors of the 5-HT2C subtype are assumed to be involved in the influence of serotonin on food intake. A polymorphism in the coding region of the gene for this receptor, resulting in a cysteine to serine substitution, has been reported. Fifty-seven somatically healthy teenage girls displaying weight loss and 91 normal-weight girls of the same age, all recruited by means of a population-based screening study, were compared with respect to this polymorphism. Subjects in the weight loss group displayed a higher frequency of the serine allele than those in the comparison group (23.7% vs. 7.7%, p =.0001). Seventy-two percent of the weight loss girls fulfilled the diagnostic criteria of anorexia nervosa, whereas 28% did not; when these two groups were separately analyzed, both differed significantly from controls with respect to serine allele frequency. The results support the notion that the studied gene may be involved in the regulation of food intake in young women.
|
|
