| 1. |
- Zettergren, Anna, 1978, et al.
(författare)
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Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.
- 2016
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Ingår i: Psychoneuroendocrinology. - Stockholm : Elsevier BV. - 1873-3360 .- 0306-4530. ; 68, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out.
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| 2. |
- Cesta, Carolyn E, et al.
(författare)
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Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort.
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 73, s. 196-203
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associations. Using the Swedish national registers, we identified all women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings (n=25,921), plus matched individuals (1:10/100) from the general population and their full-siblings. Psychiatric disorder diagnoses were identified including schizophrenia, bipolar disorder, depressive and anxiety disorders, eating disorders, personality and gender identity disorder, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and completed suicide. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression and adjusted ORs (AOR) were determined by adjustment for comorbid psychiatric disorders. Overall, women with PCOS had an increased odds of having at least one psychiatric disorder (OR=1.56 [95CI%, 1.51-1.61]). Crude ORs showed associations with nearly all psychiatric disorders included in this study. Following adjustment for comorbid psychiatric disorders, women with PCOS were still at a significantly increased risk for bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders, personality disorders, with the highest AORs for ASD (AOR=1.55 [95%CI, 1.32-1.81]) and tics (AOR=1.65 [95%CI, 1.10-2.47]). Significantly higher AORs were found for ASD in both brothers and sisters of women with PCOS, and for depressive, anxiety, and schizophrenia spectrum disorders in the sisters only. Notably, the crude ORs for attempted suicide were 40% higher in women with PCOS and 16% higher in their unaffected sisters. However, the AORs were greatly attenuated indicating that underlying psychiatric comorbidity is important for this association. Women with PCOS had higher risks for a range of psychiatric disorders not shown before. Elevated risk in their siblings suggests shared familial factors between PCOS and psychiatric disorders. This study is an important first step towards identifying the underlying mechanisms for risk of psychiatric disorders in women with PCOS. Health professionals treating women with PCOS should be aware that these patients - as well as their family members - are important targets for mental health care.
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| 3. |
- Engberg, Hedvig, et al.
(författare)
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Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.
- 2015
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 60, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n=335) born between January 1915 and January 2010 were compared with aged-matched female (n=33500) and male controls (n=33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.
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| 4. |
- Gustafsson, Per E, et al.
(författare)
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Does quantity have a quality all its own? Cumulative adversity and up- and down-regulation of circadian salivary cortisol levels in healthy children.
- 2010
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 35:9, s. 1410-1415
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Tidskriftsartikel (refereegranskat)abstract
- Findings have been divergent regarding the direction of basal cortisol dysregulations resulting from stressor exposure, and seem to differ between young people and adults. Accumulated stress exposure has been suggested to be a risk factor for the development of hypocortisolism. This cross-sectional study aims to examine the impact of cumulative adversity, i.e., the number of adversities, on diurnal salivary cortisol levels, including the cortisol awakening response (CAR), in children without psychiatric disorder. The sample consisted of 130 children (mean age 12.8 years), representing one in each twin pair included in the population-based Child and Adolescent Twin Study in Sweden (CATSS). Information about socioeconomic disadvantage, negative life events and potentially traumatic life events were collected by telephone interview and questionnaires, with parents as informants. Salivary cortisol sampling was performed in the home during two school days: at awakening, +30 min post-awakening, and at bedtime. Results showed that the number of adversities was related to the CAR, diurnal decline and +30 min post-awakening cortisol levels. Children with a moderate amount of cumulative adversity displayed high cortisol measures, while those with a high amount (3 or more) of adversities instead showed levels similar to the non-exposed group, yielding an inverse U-pattern of the association between cortisol and adversity. These results indicate that the accumulation of adversity might be an explanation of patterns of basal cortisol up-regulation in children and that those most severely exposed can exhibit an early stage of down-regulation, an issue which should be further examined in longitudinal studies.
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| 5. |
- Vestlund, Jesper, et al.
(författare)
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Ghrelin and aggressive behaviours—Evidence from preclinical and human genetic studies
- 2019
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 104, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Aggressive behaviour is of crucial importance in the defence for limited resources including food and mates and involves central serotonin as well as dopamine signalling. As ghrelin modulates food intake and sexual behaviour we initially investigated the hypothesis that central ghrelin signalling regulates aggressive behaviour in the resident intruder paradigm in male mice. Moreover, interaction between ghrelin signalling and serotonergic, noradrenergic as well as dopaminergic neurotransmission in aggression was investigated. The relevance of ghrelin for human aggression per se as well as for aggression induced by alcohol was evaluated in a human genetic association study comprising young men (n = 784) from the normal population assessed for anti-social behaviours. The present study demonstrates that central ghrelin infusion, but not ghrelin administered systemically, increases aggression. Moreover aggressive behaviour is decreased by pharmacological suppression of the growth hormone secretagogue receptor-1 A (GHSR-1A) by JMV2959. As indicated by the ex vivo biochemical data serotonin, rather than dopamine or noradrenaline, in amygdala may have central roles for the ability of JMV2959 to reduce aggression. This link between central serotonin, GHSR-1A and aggression is further substantiated by the behavioural data showing that JMV2959 cannot decrease aggression following depletion of central serotonin signalling. The genetic association study demonstrates that males carrying the Leu72Leu genotype of the pre-pro-ghrelin gene and displaying hazardous alcohol use are more aggressive when compared to the group carrying the Met-allele. Collectively, this contributes to the identification of central ghrelin pathway as an important modulator in the onset of aggressive behaviours in male mice.
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| 6. |
- Zettergren, Anna, 1978, et al.
(författare)
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Associations between polymorphisms in sex steroid related genes and autistic-like traits.
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:11, s. 2575-2584
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences in psychiatric disorders are common, which is particularly striking in autism spectrum disorders (ASDs) that are four times more prevalent in boys. High levels of testosterone during early development have been hypothesized to be a risk factor for ASDs, supported by several studies showing fetal testosterone levels, as well as indirect measures of prenatal androgenization, to be associated with ASDs and autistic-like traits (ALTs). Further, the importance of sex steroid related genes in ASDs is supported by studies reporting associations between polymorphisms in genes involved in sex steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was to investigate possible associations between 29 single nucleotide polymorphisms (SNPs) in eight genes related to sex steroids and autistic features. Individuals included in the study belong to a subset (n=1771) from The Child and Adolescent Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs, rs2747648 located in the 3'-UTR of ESR1 encoding the estrogen receptor alpha and rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly significant associations with ALTs were found in boys and girls, respectively. The results of the present study suggest that SNPs in sex steroid related genes, known to affect gene expression (rs2747648 in ESR1) and enzymatic activity (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In conclusion, the current findings provide further support for a role of sex steroids in the pathophysiology of ASDs.
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