| 1. |
- Damberg, Mattias, et al.
(författare)
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Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder.
- 2005
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 377:1, s. 49-52
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Ekman, Agneta, 1961, et al.
(författare)
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Low density and high affinity of platelet [3H]paroxetine binding in women with bulimia nervosa.
- 2006
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Ingår i: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 142:2-3, s. 219-23
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Eriksson, Olle, 1954-, et al.
(författare)
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Ovarian morphology in premenstrual dysphoria
- 2012
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 37:6, s. 742-751
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.
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| 4. |
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| 5. |
- Landén, Mikael, 1966, et al.
(författare)
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Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.
- 2001
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Ingår i: Psychopharmacology. - 0033-3158. ; 155:3, s. 292-8
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: It is well established that serotonin reuptake inhibitors (SRIs) are effective for the treatment of premenstrual dysphoria (PMD), but the receptor subtype(s) mediating this effect of serotonin have yet not been identified. OBJECTIVE: In this trial, the possible efficacy of buspirone, a partial 5HT1A receptor agonist, and nefazodone, a combined SRI and 5HT2 receptor antagonist, was evaluated in women with PMD. METHODS: After a three-menstrual-cycle screening phase, patients were randomised to buspirone (n=19), nefazodone (n=22) or placebo (n=22). During the first two treatment cycles, patients were taking the drug during the luteal phase only (mean +/- SD daily dose of buspirone: 21 +/- 6 mg; nefazodone: 228 +/- 54 mg). During the subsequent two cycles, the medication was taken each day of the menstrual cycle (mean daily dose of buspirone: 27 +/- 10 mg; nefazodone: 304 +/- 95 mg). RESULTS: With respect to self-rated global improvement, buspirone (P<0.001) but not nefazodone was significantly superior to placebo. While buspirone appeared to reduce self-rated irritability (visual analogue scale) more effectively than placebo, other self-rated symptoms did not differ markedly between the groups. The side-effects were mild, and sexual dysfunction was not significantly more common in patients given buspirone or nefazodone than in those given placebo. CONCLUSION: It is suggested that buspirone is mildly effective for premenstrual irritability. In patients experiencing sexual dysfunction when treated with an SRI, buspirone may be a useful alternative.
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| 6. |
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| 7. |
- Melke, Jonas, 1971, et al.
(författare)
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Serotonin transporter gene polymorphisms and platelet [3H] paroxetine binding in premenstrual dysphoria.
- 2003
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Ingår i: Psychoneuroendocrinology. - 0306-4530. ; 28:3, s. 446-58
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate if women with premenstrual dysphoria differ from controls with respect to the number of platelet serotonin transporters, and with respect to three polymorphisms in the gene coding for the serotonin transporter: a 44 base pair insertion/deletion in the promoter region, a variable number of tandem repeats in the second intron, and a single nucleotide polymorphism in the 3' untranslated region. Also, the possible relationship between the three polymorphisms and platelet serotonin transporter density was analyzed. The density of platelet [(3)H]paroxetine binding sites was significantly lower in women with premenstrual dysphoria than in controls, but patients and controls did not differ with respect to allele or genotype frequency for any of the three polymorphisms examined. A significant association between the number of platelet serotonin transporters and the promoter polymorphism was observed, subjects being homozygous for the short (deletion) variant having higher platelet serotonin transporter density than subjects carrying the long (insertion) allele. The results support the assumption that serotonin-related psychiatric disorders-such as premenstrual dysphoria-may be associated with a reduction in platelet [(3)H]paroxetine binding, but argue against the notion that this reduction is due to certain variants of the serotonin transporter gene being more common in patients than in controls.
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| 8. |
- Sundblad-Elverfors, Charlotta, 1959, et al.
(författare)
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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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Ingår i: Journal of clinical psychopharmacology. - : Ovid Technologies (Wolters Kluwer Health). - 0271-0749. ; 25:1, s. 85-8
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Alm, Charlotta, et al.
(författare)
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Classification of offenders with mental health problems and problematic substance use using the Addiction Severity Index version 6 : Analysis of three-year follow-up data and predictive validity
- 2014
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Ingår i: Mental Health and Substance Use. - Abingdon : Routledge. - 1752-3281 .- 1752-3273. ; 7:4, s. 431-445
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Tidskriftsartikel (refereegranskat)abstract
- Previous research is scarce on the problems and needs of the “triply troubled” – among offenders with mental health problems and problematic substance use. Classifying this population into clusters based on problem profiles may provide information about individual needs for treatment. In a previous study, we identified four clusters of triply troubled: less troubled, severely triply troubled, triply troubled with medical problems, and working triply troubled. The present study explored the stability and predictive validity of these clusters in a naturalistic design. In total, 125 triply troubled individuals included in any of the four clusters were followed for approximately three years with regard to their inpatient and outpatient treatment participation. They were also interviewed with the 6th version of the Addiction Severity Index, the Psychopathy Checklist–Revised, and the World Health Organization Quality of Life–Bref. The main finding of the study was that on average the participants of all four clusters exhibited substantial improvements over the course of time but that improvements were cluster-specific rather than sample-specific. Implications of the study are discussed.
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| 10. |
- Altgärde, Noomi, 1983, et al.
(författare)
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Mucin-like region of herpes simplex virus type 1 attachment protein gC modulates the virus-glycosaminoglycan interaction.
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:35, s. 21473-21485
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Tidskriftsartikel (refereegranskat)abstract
- Glycoprotein C (gC) mediates the attachment of herpes simplex virus type 1 (HSV-1) to susceptible host cells by interacting with glycosaminoglycans (GAGs) on the cell surface. gC contains a mucin-like region located near the GAG-binding site, which may affect the binding activity. Here, we address this issue by studying an HSV-1 mutant lacking the mucin- like domain in gC and the corresponding purified mutant protein (gCΔmuc), in cell culture and GAG-binding assays, respectively. The mutant virus exhibited two functional alterations as compared to native HSV-1, i.e. decreased sensitivity to GAG-based inhibitors of virus attachment to cells, and reduced release of viral particles from the surface of infected cells. Kinetic and equilibrium binding characteristics of purified gC were assessed using surface plasmon resonance-based sensing together with a surface platform consisting of end-on immobilized GAGs. Both native gC and gCΔmuc bound via the expected binding region to chondroitin sulfate and sulfated hyaluronan but not to the non-sulfated hyaluronan, confirming binding specificity. In contrast to native gC, gCΔmuc exhibited a decreased affinity for GAGs and a slower dissociation, indicating that once formed, the gCΔmuc-GAG complex is more stable. It was also found that a larger number of gCΔmuc bound to a single GAG chain, compared to native gC. Taken together, our data suggest that the mucin-like region of HSV-1 gC is involved in the modulation of the GAG-binding activity, a feature of importance both for unrestricted virus entry into the cells and release of newly produced viral particles from infected cells.
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