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Autism androgen

Carolyn E Cesta, Mattias Månsson, Camilla Palm, Paul Lichtenstein, Anastasia N Iliadou, Mikael Landén
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...
November 2016: Psychoneuroendocrinology
Karson T F Kung, Debra Spencer, Vickie Pasterski, Sharon Neufeld, Vivette Glover, Thomas G O'Connor, Peter C Hindmarsh, Ieuan A Hughes, Carlo L Acerini, Melissa Hines
BACKGROUND: There is a marked male preponderance in autism spectrum conditions. The extreme male brain theory and the fetal androgen theory of autism suggest that elevated prenatal testosterone exposure is a key contributor to autistic traits. The current paper reports findings from two separate studies that test this hypothesis. METHODS: A parent-report questionnaire, the Childhood Autism Spectrum Test (CAST), was employed to measure autistic traits in both studies...
July 27, 2016: Journal of Child Psychology and Psychiatry, and Allied Disciplines
Miguel Perez-Pouchoulen, Marta Miquel, Paul Saft, Brenda Brug, Rebeca Toledo, Maria Elena Hernandez, Jorge Manzo
Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points...
October 2016: International Journal of Developmental Neuroscience
Anna Zettergren, Sara Karlsson, Daniel Hovey, Lina Jonsson, Jonas Melke, Henrik Anckarsäter, Paul Lichtenstein, Sebastian Lundström, Lars Westberg
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)...
June 2016: Psychoneuroendocrinology
Anna Pivovarciova, Jaroslava Durdiakova, Katarina Babinska, Aneta Kubranska, Lenka Vokalova, Gabriel Minarik, Peter Celec, Marianna Murin, Daniela Ostatnikova
INTRODUCTION: Autism spectrum disorders (ASD) and hyperactivity symptoms exhibit an incidence that is male-biased. Thus androgen activity can be considered a plausible biological risk factor for these disorders. However, there is insufficient information about the association between increased androgen activity and hyperactivity symptoms in children with ASD. METHODS: In the present study, the relationship between parameters of androgenicity (plasmatic testosterone levels and androgen receptor sensitivity) and hyperactivity in 60 boys (age 3-15) with ASD is investigated...
2016: PloS One
Christina Chen, John Darrell Van Horn
Examining sex differences in the brain has been historically contentious but is nonetheless important for advancing mental health for both girls and boys. Unfortunately, females in biomedical research remain underrepresented in most mental health conditions including autism spectrum disorders (ASD), even though equal inclusion of females would improve treatment for girls and yield benefits to boys. This review examines sex differences in the relationship between neuroanatomy and neurogenetics of ASD. Recent findings reveal that girls diagnosed with ASD exhibit more intellectual and behavioral problems compared to their male counterparts, suggesting that girls may be less likely diagnosed in the absence of such problems or that they require a higher mutational load to meet the diagnostic criteria...
January 19, 2016: Brain Imaging and Behavior
K Kosidou, C Dalman, L Widman, S Arver, B K Lee, C Magnusson, R M Gardner
Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring...
October 2016: Molecular Psychiatry
Ayhan Bilgiç, Özlem Bilgiç, Sabri Hergüner, Hilmi Cevdet Altınyazar
AIM: Many psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), disruptive behavioral disorders, autism spectrum disorders, and some psychiatric characteristics, such as poor empathizing, are regarded to be related to elevated levels of androgens or androgen sensitivity. Thus, numerous studies have investigated the potential association between androgen-related physical diseases and these psychiatric conditions. Idiopathic hirsutism (IH) is a disease characterized by an increased sensitivity of the pilosebaceous unit to circulating androgens in women...
July 2015: International Journal of Trichology
Keely Cheslack-Postava, Ezra Susser, Kayuet Liu, Peter S Bearman
BACKGROUND: Sibling sex ratios have been applied as an indirect test of a hypothesized association between prenatal testosterone levels and risk for autism, a developmental disorder disproportionately affecting males. Differences in sibling sex ratios between those with and without autism would provide evidence of a shared risk factor for autism and offspring sex. Conclusions related to prenatal testosterone, however, require additional assumptions. Here, we used directed acyclic graphs (DAGs) to clarify the elements required for a valid test of the hypothesis that sibling sex ratios differ between children with and without autism...
2015: PloS One
Timothy R Rice
Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic-pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen-mediated organizational effects on the developing brain...
September 10, 2015: International Journal of Adolescent Medicine and Health
Esha S L Jamnadass, Jeffrey A Keelan, Lauren P Hollier, Martha Hickey, Murray T Maybery, Andrew J O Whitehouse
BACKGROUND: Prenatal androgen exposure has been hypothesized to be linked to autism spectrum disorder (ASD). While previous studies have found a link between testosterone levels in amniotic fluid and autistic-like traits, a similar relationship has not been found for testosterone in umbilical cord blood. However, it may be the net biological activity of multiple androgens and estrogens that influences postnatal effects of prenatal sex steroids. Accordingly, composite levels of androgens (A) and estrogens (E) were investigated, along with their ratio, in relation to autistic-like traits in young adulthood...
2015: Journal of Neurodevelopmental Disorders
Nikola Nowack, Jürgen Wittsiepe, Monika Kasper-Sonnenberg, Michael Wilhelm, Axel Schölmerich
BACKGROUND: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits. OBJECTIVES: We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood. METHODS: We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry...
2015: PloS One
Arzu Hergüner, Sabri Hergüner
OBJECTIVES: The androgen theory of autism suggests that masculinizing effect of fetal androgens may play a role in the expression of autism. Recent evidence showed that excessive prenatal androgen exposure might delay age at menarche (AAM). The aim of this study was to investigate the relation between autistic traits and AAM in a sample of nonclinical female university students. METHODS: Autistic traits were measured using the Autism Spectrum Quotient (AQ), and AAM was questioned by retrospective self-reports...
January 2016: American Journal of Human Biology: the Official Journal of the Human Biology Council
Masaru Katoh
ASXL1, ASXL2 and ASXL3 are epigenetic scaffolds for BAP1, EZH2, NCOA1, nuclear receptors and WTIP. Here, functional proteomics of the ASXL family members are reviewed with emphasis on mutation spectra, the ASXM2 domain and the plant homeodomain (PHD) finger. Copy number gains of ASXL1 occur in chromosome 20q11.2 duplication syndrome and cervical cancer. Truncation mutations of ASXLs occur in autism, Bohring-Opitz and related syndromes, hematological malignancies and solid tumors, such as prostate cancer, breast cancer and high-grade glioma, which are gain- or loss-of-function mutations...
June 2015: Expert Review of Proteomics
Walter Lichtensteiger, Catherine Bassetti-Gaille, Oliver Faass, Marta Axelstad, Julie Boberg, Sofie Christiansen, Hubert Rehrauer, Jelena Kühn Georgijevic, Ulla Hass, Andreas Kortenkamp, Margret Schlumpf
The study addressed the question whether gene expression patterns induced by different mixtures of endocrine disrupting chemicals (EDCs) administered in a higher dose range, corresponding to 450×, 200×, and 100× high-end human exposure levels, could be characterized in developing brain with respect to endocrine activity of mixture components, and which developmental processes were preferentially targeted. Three EDC mixtures, A-Mix (anti-androgenic mixture) with 8 antiandrogenic chemicals (di-n-butylphthalate, diethylhexylphthalate, vinclozolin, prochloraz, procymidone, linuron, epoxiconazole, and DDE), E-Mix (estrogenic mixture) with 4 estrogenic chemicals (bisphenol A, 4-methylbenzylidene camphor, 2-ethylhexyl 4-methoxycinnamate, and butylparaben), a complex mixture, AEP-Mix, containing the components of A-Mix and E-Mix plus paracetamol, and paracetamol alone, were administered by oral gavage to rat dams from gestation day 7 until weaning...
April 2015: Endocrinology
Xin-Jie Xu, Hong-Feng Zhang, Xiao-Jing Shou, Jin Li, Wei-Long Jing, Ying Zhou, Yi Qian, Song-Ping Han, Rong Zhang, Ji-Sheng Han
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent impairment in social communication and social interaction. Recent studies revealed that environmental factors, especially the intrauterine developmental environment, played important roles in the development of ASD. It is hypothesized that maternal hyperandrogenism during pregnancy may increase the susceptibility of the fetus to ASD. In the present study, pregnant rats were treated with a low dose of letrozole (1μg/kg/day) in an attempt to produce a hyperandrogenic intrauterine environment for the developing fetus...
January 2015: Physiology & Behavior
Agnieszka Butwicka, Paul Lichtenstein, Mikael Landén, Anna S Nordenvall, Anna Nordenström, Agneta Nordenskjöld, Louise Frisén
BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients...
February 2015: Journal of Child Psychology and Psychiatry, and Allied Disciplines
A Skakkebaek, A Bojesen, M K Kristensen, A Cohen, D M Hougaard, J M Hertz, J Fedder, P Laurberg, M Wallentin, J R Østergaard, A D Pedersen, C H Gravholt
Klinefelter syndrome (KS, 47,XXY) is associated with increased psychiatric morbidity and cognitive disabilities, although the neuropsychological phenotype shows great variability. Androgen receptor polymorphism (CAG repeat length), skewed X-chromosome inactivation and parent-of-origin of the extra X-chromosome have been suggested to influence cognitive function and psychological traits. These issues have not been clarified for KS patients. We studied X-chromosome inactivation pattern, CAG repeat length and parent-of-origin in relation to educational and cohabitation status, personality and autism traits, psychological distress, cognitive function and brain volumes in 73 KS patients and 73 controls...
July 2014: Andrology
Koichiro Watanabe, Toshiaki Kikuchi
The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children...
2014: Seishin Shinkeigaku Zasshi, Psychiatria et Neurologia Japonica
Alexa Pohl, Sarah Cassidy, Bonnie Auyeung, Simon Baron-Cohen
BACKGROUND: Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms ('steroidopathy') in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC...
2014: Molecular Autism
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