| 1. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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The extreme male brain revisited: gender coherence in adults with autism spectrum disorder
- 2012
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Ingår i: British Journal of Psychiatry. - London, United Kingdom : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:2, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- Background The 'extreme male brain' theory suggests that autism spectrum disorder (ASD) is an extreme variant of male intelligence. However, somewhat paradoxically, many individuals with ASD display androgynous physical features regardless of gender. Aims To assess physical measures, supposedly related to androgen influence, in adults with and without ASD. Method Serum hormone levels, anthropometry, the ratio of 2nd to 4th digit length (2D:4D) and psychiatric symptomatology were measured in 50 adults with high-functioning ASD and age- and gender-matched neurotypical controls. Photographs of face and body, as well as voice recordings, were obtained and assessed with respect to gender coherence, blindly and independently, by eight assessors. Results Women with ASD had higher total and bioactive testosterone levels, less feminine facial features and a larger head circumference than female controls. Men in the ASD group were assessed as having less masculine body characteristics and voice quality, and displayed higher (i.e. less masculine) 2D:4D ratios, but similar testosterone levels to controls. Androgynous facial features correlated strongly and positively with autistic traits measured with the Autism-Spectrum Quotient in the total sample. In males and females with ASD dehydroepiandrosterone sulfate did not decrease with age, in contrast to the control group. Conclusions Women with ASD had elevated testosterone levels and several masculinised characteristics compared with controls, whereas men with ASD displayed several feminised characteristics. Our findings suggest that ASD, rather than being characterised by masculinisation in both genders, may constitute a gender defiant disorder.
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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. |
- Hansson, Caroline, 1981, et al.
(författare)
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A possible association between panic disorder and a polymorphism in the preproghrelin gene
- 2013
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Ingår i: Psychiatry Research. - : Elsevier. - 0165-1781 .- 1872-7123. ; 206:1, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.
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| 5. |
- Hieronymus, Fredrik, et al.
(författare)
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The alleged ineffectiveness of SSRIs in depression is an artefact caused by the use of an inappropriate measure of efficacy
- 2014
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Ingår i: International Journal of Neuropsychopharmacology vol. 17 Supplement 1. 29th CINP World Congress of Neuropsychopharmacology, Vancouver, Canada, 22–26 June 2014. - New York : Cambridge University Press. - 1461-1457 .- 1469-5111.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Many studies have questioned if summation of the scores of the 17 disparate items constituting the Hamilton Depression Rating Scale (HDRS-17) is a reliable index of severity in depression; yet the cur- rent questioning of the ef fi cacy of antidepressant drugs is to a large extent based on the assumption that response to treatment is reliably re fl ected by this instrument. We aimed to investigate the possibility that the shortcom- ings of the HDRS may contribute to the failure of antidepressants to out- perform placebo in many trials. Methods: We analyzed thirteen industry-sponsored trials of selective serotonin reuptake inhibitors (SSRIs) comprising twenty-four drug- placebo comparisons and including patient-level data from 5381 subjects (administered paroxetine, citalopram, fl uoxetine, or placebo), the aim being to assess what the outcome would have been if the single item de- pressed mood (rated 0 – 4) had been used as measure of ef fi cacy. Results: While 12 out of 24 comparisons (50%) revealed a signi fi cant difference between active drug and placebo at week 6 with respect to re- duction in HDRS-17-sum, 23 out of 24 comparisons (96%) showed the ac- tive drug to be superior to placebo in reducing depressed mood. Correspondingly, a pooled analysis of all cases showed the effect size when assessed using the HDRS-17-sum to be 0.30, whereas it, when mea- sured using the depressed mood item alone, was 0.42. Conclusion: While not claiming that measuring one item only is the most appropriate way of recording symptom severity in depression, we do suggest that the inclusion of a number of varying symptoms in the as- sessment, some of which may be side-effects of treatment and/or are unre- lated to the disorder, reduces the sensitivity to detect a difference between active drug and placebo. This lack of sensitivity of HDRS-17 might partly explain why a high fraction of antidepressant trials fail to reveal a signi fi - cant difference between treatment groups
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| 6. |
- 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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| 7. |
- Andersson, Evelyn, et al.
(författare)
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Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.MethodParticipants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.ResultsAt long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.ConclusionsNone of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.
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| 8. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder: A replication
- 2010
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Ingår i: Psychiatry Research. - : Elsevier Science B.V., Amsterdam.. - 0165-1781 .- 1872-7123. ; 178:1, s. 196-198
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Tidskriftsartikel (refereegranskat)abstract
- The association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder was studied in a Swedish sample of 211 patients and 452 controls. We found a significant excess of the Val allele in both male and female patients, the latter but not the former finding being in line with previous studies.
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| 9. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene
- 2011
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Ingår i: PSYCHIATRIC GENETICS. - : Rapid Communications of Oxford Ltd. - 0955-8829 .- 1473-5873. ; 21:2, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Background Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. Methods We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. Results Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. Conclusion Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.
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| 10. |
- 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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