| 91. |
- Walum, Hasse, et al.
(författare)
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Variation in the oxytocin receptor gene is associated with pair-bonding and social behavior
- 2012
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Ingår i: Biological Psychiatry. - New York, USA : Elsevier. - 0006-3223 .- 1873-2402. ; 71:5, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- Background: In specific vole and primate species the neuropeptide oxytocin plays a central role in the regulation of pair-bonding behavior. Here we investigate the extent to which genetic variants in the oxytocin receptor gene (OXTR) are associated with pair-bonding and related social behaviors in humans.Methods: We first genotyped twelve single nucleotide polymorphisms (SNPs) in the TOSS (Twin and Offspring Study in Sweden) (n = 2309) and the TCHAD (Swedish Twin Study of Child and Adolescent Development) (n = 1240), comprising measures of self-reported pair-bonding behavior. In the TOSS sample we further investigated one of the SNPs for measures of marital status and quality. Moreover, in the TCHAD sample we explored the longitudinal relationship between precursors of pair-bonding during childhood and subsequent behavior in romantic relationships. Finally, in the TCHAD study and in the Child and Adolescent Twin Study of Sweden (CATSS) (n = 1771), the association between the same SNP and childhood behaviors was investigated.Results: One SNP (rs7632287) in OXTR was associated with traits reflecting pair-bonding in women in the TOSS and TCHAD samples. In girls the rs7632287 SNP was further associated with childhood social problems, which longitudinally predicted pair-bonding behavior in the TCHAD sample. This association was replicated in the CATSS sample in which an association between the same SNP and social interaction deficit symptoms from the autism spectrum was detected.Conclusion: These results suggest an association between variation in OXTR and human pair-bonding and other social behaviors, possibly indicating that the well-described influence of oxytocin on affiliative behavior in voles could also be of importance for humans.
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| 92. |
- Westberg, Lars, 1973, et al.
(författare)
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Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women.
- 2003
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 8:1, s. 118-22
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens are known to play a key role in the regulation of various aspects of behavior. In order to study the potential contribution of genetic variation in the estrogen receptor (ER) alpha to specific personality traits, we investigated a repeat polymorphism in the ER alpha gene in 172 42-year-old women who had been assessed using the Karolinska Scales of Personality (KSP). Based on the hypothesis that there is a relationship between the length of a repeat polymorphism and gene function,(1) the alleles were divided into two groups: short and long. In order to elucidate the possible influence of the ER alpha gene on the different aspects of personality measured by means of the KSP, the possible association between this gene and four different factors ('neuroticism', 'psychoticism', 'non-conformity', and 'extraversion') was analysed. 'Neuroticism', 'psychoticism', and 'non-conformity' all appeared to be associated with the ER alpha gene. After correction for multiple comparisons by means of permutation analysis, the associations with the factor 'non-conformity'--including the subscales 'indirect aggression' and 'irritability'--and the factor 'psychoticism'--including the subscale 'suspicion'--remained significant. The results suggest that the studied dinucleotide repeat polymorphism of the ER alpha gene may contribute to specific components of personality.
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| 93. |
- Westberg, Lars, 1973, et al.
(författare)
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Association between a polymorphism of the 5-HT2C receptor and weight loss in teenage girls.
- 2002
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - 0893-133X. ; 26:6, s. 789-93
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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.
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| 94. |
- Westberg, Lars, 1973, et al.
(författare)
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Association between the estrogen receptor beta gene and age of onset of Parkinson's disease.
- 2004
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 29:8, s. 993-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the potential contribution of genetic variants in the estrogen receptor beta gene to the aetiology of Parkinson's disease (PD). Several lines of evidence from human and animal studies suggest a protective role for estrogen in PD. Recently the estrogen receptor beta subtype was reported to be an important mediator of estrogen actions in the nigrostriatal dopamine system. Two single nucleotide polymorphisms at position 1730 and 1082 in the ER beta gene were genotyped, using pyrosequencing, in 260 patients with PD and 308 controls recruited from the Swedish population. Neither of the two estrogen receptor beta polymorphisms was associated with an increased risk for PD. However, the G allele of the A1730G polymorphism was more frequent in patients with an early age of onset than in patients with a late age of onset of PD (P = 0.006). Patients carrying the GG genotype had an odds ratio of 2.2 for having an early onset of PD compared to non-carriers. In conclusion, our results indicate that genetic variation in the estrogen receptor beta gene may influence the age of onset of PD.
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| 95. |
- Westberg, Lars, 1973, et al.
(författare)
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Colocalization of connexin 36 and corticotropin-releasing hormone in the mouse brain.
- 2009
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Ingår i: BMC neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 10:41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gap junction proteins, connexins, are expressed in most endocrine and exocrine glands in the body and are at least in some glands crucial for the hormonal secretion. To what extent connexins are expressed in neurons releasing hormones or neuropeptides from or within the central nervous system is, however, unknown. Previous studies provide indirect evidence for gap junction coupling between subsets of neuropeptide-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Here we employ double labeling and retrograde tracing methods to investigate to what extent neuroendocrine and neuropeptide-containing neurons of the hypothalamus and brainstem express the neuronal gap junction protein connexin 36. RESULTS: Western blot analysis showed that connexin 36 is expressed in the PVN. In bacterial artificial chromosome transgenic mice, which specifically express the reporter gene Enhanced Green Fluorescent Protein (EGFP) under the control of the connexin 36 gene promoter, EGFP expression was detected in magnocellular (neuroendocrine) and in parvocellular neurons of the PVN. Although no EGFP/connexin36 expression was seen in neurons containing oxytocin or vasopressin, EGFP/connexin36 was found in subsets of PVN neurons containing corticotropin-releasing hormone (CRH), and in somatostatin neurons located along the third ventricle. Moreover, CRH neurons in brainstem areas, including the lateral parabrachial nucleus, also expressed EGFP/connexin 36. CONCLUSION: Our data indicate that connexin 36 is expressed in subsets of neuroendocrine and CRH neurons in specific nuclei of the hypothalamus and brainstem.
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| 96. |
- 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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| 97. |
- Westberg, Lars, 1973
(författare)
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Polymorphism in sex steroid-related genes. Effects on hormone levels and behavior
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genetic factors are important for variations between individuals with respect to most humantraits and diseases. Sex steroids are of profound importance for reproduction, metabolism,cardiovascular function and bone formation. They are potent regulators of their ownsynthesis as well as of that of other hormones, including prolactin. They also exert markedinfluence on the brain, and are hence of probable importance for various normal behaviors,including sexual activity and aggression, as well as for a number of neuropsychiatricdisorders.The purpose of this thesis was to explore how various aspects of the human phenotypemay be influenced by genetic variants polymorphisms - in genes encoding proteins ofimportance for the synthesis and metabolism of sex steroids, receptors for sex steroids, andcoregulators of these receptors. The studies were focused on the possible influence of sexsteroid-related genes on brain and behavior. In addition, effects on hormone levels in serumwere analyzed.Observations: 1) Repeat polymorphisms in the genes encoding the androgen receptor(AR) and the estrogen receptor (ER) beta were associated with serum levels of androgens inwomen. 2) The same ER beta repeat polymorphism, as well as a single nucleotidepolymorphism (SNP) in the progesterone receptor (PR) gene, earlier shown to be ofimportance for the expression of this gene, were associated with serum levels of prolactin. 3)A repeat polymorphism in the gene encoding ER alpha was associated with personality traitsrelated to anxiety and irritability in women. 4) The same variant of the PR genepolymorphism that was associated with prolactin levels was also associated with panicdisorder in women but not in men. 5) A SNP in the ER beta gene was associated with anearly age of onset of Parkinson s disease, but not with the disease per se. 6) In spite of thefact that is well established that women with premenstrual dysphoric disorder displayaberrant brain responsiveness to sex steroids, no differences between patients with thiscondition and controls with respect to a large number of polymorphisms in sex steroidrelatedgenes were observed.Conclusions: All the studies were based on a priori hypotheses regarding the possiblerelationship between the studied genes and the various aspects of the phenotype beinginvestigated. A number of possible associations were found, as described above, none ofwhich had been reported in the literature before. Whereas some of these findings havesubsequently been confirmed in independent studies, or are more or less in line with findingsreported by other researchers, such as the associations between the AR gene and androgenlevels, and between the ER alpha gene and personality traits, others should be regarded aspreliminary until replicated in other populations. The main conclusion of this thesis is thatsex steroid-related genes may be relevant candidates not only for the study of traits anddisorders that are obviously related to sex steroids, such as those related to reproduction,but also for further studies of inter-individual differences with respect to normal behavior aswell as with respect to the susceptibility to various neuropsychiatric disorders.
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| 98. |
- Westberg, Lars, 1973, et al.
(författare)
-
Polymorphisms in oestrogen and progesterone receptor genes: possible influence on prolactin levels in women.
- 2004
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 61:2, s. 216-23
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Oestrogen and progesterone are known to influence the release of human prolactin. The present study was undertaken in order to investigate the possible influence of polymorphisms of the genes encoding the oestrogen receptor (ER)alpha, ERbeta and the progesterone receptor (PGR), on prolactin levels in premenopausal women. DESIGN AND MEASUREMENTS: Serum levels of prolactin were measured in the follicular phase of the menstrual cycle. Subjects were genotyped with respect to a TA repeat polymorphism of the ERalpha gene, a CA repeat polymorphism of the ERbeta gene, and two polymorphisms of the PGR gene: one insertion polymorphism (PROGINS) and one single nucleotide polymorphism (G331A). SUBJECTS: A population-based cohort of 270 42-year-old women. RESULTS: The CA repeat polymorphism of the ERbeta gene and the G331A polymorphism of the PGR gene appeared to be associated with prolactin levels. In contrast, we found no evidence for an influence of the PROGINS polymorphism of the PGR gene or the TA repeat polymorphism of the ERalpha gene on the levels of this hormone. CONCLUSIONS: These data suggest that genetic variants of both the ERbeta and the PGR may influence prolactin release.
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| 99. |
- Westberg, Lars, 1973, et al.
(författare)
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Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women.
- 2001
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 86:6, s. 2562-8
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.
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| 100. |
- Westberg, Lars, 1973, et al.
(författare)
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Sex steroid-related candidate genes in psychiatric disorders.
- 2008
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Ingår i: Journal of psychiatry & neuroscience : JPN. - 1488-2434. ; 33:4, s. 319-30
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Tidskriftsartikel (refereegranskat)abstract
- Sex steroids readily pass the blood-brain barrier, and receptors for them are abundant in brain areas important for the regulation of emotions, cognition and behaviour. Animal experiments have revealed both important early effects of these hormones on brain development and their ongoing influence on brain morphology and neurotransmission in the adult organism. The important effects of sex steroids on human behaviour are illustrated by, for example, the effect of reduced levels of these hormones on sexual drive and conditions such as premenstrual dysphoric disorder, perimenopausal dysphoria, postpartum depression, postpartum psychosis, dysphoria induced by oral contraceptives or hormonal replacement therapy and anabolic steroid-induced aggression. The fact that men and women (as groups) differ with respect to the prevalence of several psychiatric disorders, certain aspects of cognitive function and certain personality traits may possibly also reflect an influence of sex steroids on human behaviour. The heritability of most behavioural traits, including personality, cognitive abilities and susceptibility to psychiatric illness, is considerable, but as yet, only few genes of definite importance in this context have been identified. Given the important role of sex steroids for brain function, it is unfortunate that relatively few studies so far have addressed the possible influence of sex steroid-related genes on interindividual differences with respect to personality, cognition and susceptibility to psychiatric disorders. To facilitate further research in this area, this review provides information on several such genes and summarizes what is currently known with respect to their possible influence on brain function.
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