HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes.

DNA methylation shifts in Hypothalamic-pituitary-adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

Genetic Variants Associated With Male Pedophilic Sexual Interest.

INTRODUCTION: The etiology of sexual preference disorders (paraphilias) in general and pedophilia in particular remains unknown. There are some indications of biological factors related to pedophilic interest and pedophilic disorder. AIM: To examine single-nucleotide polymorphisms (SNPs) potentially associated with pedophilic sexual interest. METHODS: The sample consisted of 1,672 men 18 to 45 years old from the Genetics of Sex and Aggression sample who had submitted saliva samples. Fifty-four SNPs were genotyped and relevant SNPs were analyzed. MAIN OUTCOME MEASURES: A self-report questionnaire designed specifically for the Genetics of Sex and Aggression sample was used to measure sexual interest in and sexual behavior toward children and adolescents. DNA extraction and genotyping were used to measure possible associations between male pedophilia and SNPs. RESULTS: Before controlling for multiple testing, statistically significant associations were found for SNPs linked to androgen, estrogen, prolactin, corticotrophin, serotonin, and oxytocin. No associations remained significant after controlling for multiple testing. CONCLUSION: The results of the present study suggest a complex biological mechanism affecting adult sexual interest in children. Very small effect sizes characterized the findings, and several polymorphisms related to different hormonal functioning were initially related to the phenotype.

Traits of autism spectrum disorders in adults with gender dysphoria.

The literature examining the co-occurrence of gender dysphoria (GD) and autistic traits has so far been limited to a series of small case studies and two systematic studies, one looking at autistic traits in gender dysphoric children and the other set within the context of the extreme male brain hypothesis and looking at adults. The current study examined this co-occurrence of GD and autistic traits in an adult population, to see whether this heightened prevalence persisted from childhood as well as to provide further comparison of MtF versus FtM transsexuals and homosexual versus nonhomosexual individuals. Using the Autistic Spectrum Quotient (AQ), 91 GD adults (63 male-to-female [MtF] and 28 female-to-male [FtM]) undertaking treatment at a gender clinic completed the AQ. The prevalence of autistic traits consistent with a clinical diagnosis for an autism spectrum disorder (ASD) was 5.5 % (n = 3 MtF and n = 2 FtM) compared to reports of clinical diagnoses of 0.5-2.0 % in the general population. In contrast to the single previous report in adults, there was no significant difference between MtF and FtM on AQ scores; however, all of those who scored above the clinical cut-off were classified as nonhomosexual with respect to natal sex. Results were considered in the context of emerging theories for the observed co-occurrence of GD and autistic traits.

Cartografiando la pedofilia: eficacia de los tratamientos y estrategias futuras / No disponible

Para orientar el trabajo de los profesionales de la salud mental que trabajan con pedófilos se necesitan evaluaciones clínicas rigurosas que aporten evidencias de la eficacia de las intervenciones psicoterapéuticas y/o psicofarmacológicas. Con ese propósito, se revisan aquí distintos hallazgos obtenidos hasta hoy en el tratamiento de los pedófilos. Aunque los hallazgos son incipientes, la literatura científica sugiere ciertas anomalías en el neurodesarrollo asociadas a tal parafilia. También hay evidencia empírica que avala la eficacia del abordaje multimodal que combina los tratamientos cognitivo- conductuales usados con medidas psicosociales y/o jurídicas. Los avances que puedan producirse en la explicación etiológica de la pedofilia ayudarán en el futuro a adoptar programas de prevención y tratamiento más eficaces

To guide the work of mental health professionals who work with pedophiles rigorous clinical evaluations that provide evidence of the effectiveness of psychotherapeutic interventions and / or psychopharmacological are needed. To that aim, here they are reviewed various actual findings in the treatment of pedophiles. While the findings are emerging, the scientific literature suggests certain neurodevelopmental abnormalities associated with such paraphilia . There is also empirical evidence supporting the effectiveness of multimodal approach combining cognitive-behavioral treatments used with psychosocial and / or legal actions. The advances that may occur in the etiological explanation of pedophilia help in the future to adopt prevention programs and more effective treatment

Hormônios pré-natais e a idéia de sexo cerebral: uma análise das pesquisas biomédicas sobre gênero e sexualidade / Prenatal hormones and the brain sex: an analysis of gender and sexuality in biomedical research

Este trabalho teve como objetivo analisar concepções de gênero e sexualidade na produção biomédica contemporânea e no processo de construção do conhecimento científico. Para isso, analisamos artigos científicos contemporâneos selecionados a partir de um levantamento na base de dados PubMed. Focamos em pesquisas sobre a teoria dos hormônios pré-natais, que propõe que comportamentos e características consideradas "femininas" ou "masculinas" são determinados, de modo inato, pelo "sexo" cerebral dos indivíduos, e que homossexuais e transexuais – por exemplo – possuiriam cérebros com um sexo discordante ao seu sexo biológico, sendo uma espécie de "hermafrodita" cerebral. Assim, através da análise dessas publicações, procuramos refletir sobre a relação entre ciência e senso comum, além dos ideais em torno da "masculinidade", "feminilidade" e "heterossexualidade" subjacentes ao conhecimento científico. Buscamos refletir também sobre a relação entre gênero, orientação sexual e desvio, e a importância concedida ao "biológico" e "inato" na sociedade contemporânea.

The aim of this study was to analyze the conceptions surrounding gender and sexuality in contemporary biomedical research and in the construction of scientific knowledge. We performed a PubMed search, focusing on papers that discussed the theory of pre-natal hormones. According to this theory, some behaviors and characteristics considered as "female" or "male" are innately determined by the individual‘s brain "sex", and homosexuals and transsexuals, for instance, have a different brain sex than their biologic sex, being a kind of a brain hermaphrodite. Therefore, through the analysis of these publications, we reflected on the relationships between science and common sense, and on the ideals of "masculinity", "feminility" and "heterossexuality" that form the basis of scientific knowledge. We also discussed the relationship between gender, sexual orientation and deviation, and the importance of the "biological" and "innate" given by contemporary society.

Behavioural phenotype in Börjeson-Forssman-Lehmann syndrome.

BACKGROUND: Börjeson-Forssman-Lehmann syndrome (BFLs) is an X-linked inherited disorder characterised by unusual facial features, abnormal fat distribution and intellectual disability. As many genetically determined disorders are characterised not only by physical features but also by specific behaviour, we studied whether a specific behavioural phenotype exists in BFLs. METHODS: We studied in detail the behaviour of four molecularly proven BFLs patients, and reviewed available literature on BFLs specifically for behavioural characteristics. RESULTS: Behaviour in persons with BFLs is in general friendly, but can be challenging with externalising and thrill-seeking features. Social skills are good. However, variation among patients is wide. Three patients from a single family showed expressed hypersexual behaviour. This was not present in other patients. CONCLUSION: In BFLs a specific behavioural phenotype exists and in behaviour general is challenging besides a friendly habit. Within single families more problematic behaviour may occur. Further behavioural and molecular analysis of a larger group of patients is warranted to determine whether a genotype-behavioural phenotype correlation exists.

Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.

Obsessive-compulsive disorder and paraphilia in a monozygotic twin pair.

We report OCD and paraphilia in two male members of triplets (the two males being monozygotic twins), and discuss the possible aetiological factors for this previously unreported occurrence. We suggest that patients presenting with paraphilia should be examined for OCD and that a detailed sexual history should be obtained in all patients with OCD.

Is there familial transmission of pedophilia?

A naturalistic, double-blind, family history comparison of sexual deviancy in the first degree relatives of inpatients with pedophilia and nonpedophilic paraphilia was done. Both proband groups were similar in demographic characteristics, except that pedophiles had a later onset of illness and were older during hospitalization. All patients were men. Sexual deviancy was found in 18.5 per cent of the families of paraphiliacs; only 3 per cent of a psychiatric control group had a family member with sexual deviancy. The preponderance of affected relatives were men. The types of sexual deviancy found in the families of the groups differed. Sexual deviancy among the pedophiles' families consisted of pedophilia. In families of nonpedophilic paraphiliacs, sexual deviancy was predominantly a paraphilia not involving children. These data suggest that pedophilia is familial; however, further studies are needed to delineate the manner of transmission. Nonetheless, pedophilia is found more frequently in families of pedophiles than in families of nonpedophilic paraphiliacs. This indicates specificity in the familial transmission. Thus pedophilia may be independent of the other paraphilias.

Biology of sexuality inborn determinants of human sexual response.

Opinions vary on the relative importance of biological and learning processes in the aetiology of sexual expression and deviance. The structure of personality, consistency of fantasy patterns, and the familial nature of homosexuality hint at a biological anlage. Research with the HY-antigen complex and X chromosome, and the elucidation of the interactions of intrauterine testosterone and its products with the foetal brain and neurotransmitters, have given us new models to understand the programming of sexuality. However, gonadotrophin feedback is not relevant as an indicator of brain feminization in primates and man. Finally, the interaction of masculinization and defeminization provides us with a model for understanding homosexual behaviour.

A case of familial exhibitionism in Tourette's syndrome successfully treated with haloperidol.

The authors describe a 32-year-old man with Gilles de la Tourette's syndrome whose most severe symptom was exhibitionism. Treatment with low doses of haloperidol eliminated all exhibitionistic urges. This patient's oldest son has multiple tics and his nephew has Tourette's syndrome with mild exhibitionism. The major implications of this case are that 1) all patients with compulsive-type exhibitionism should be carefully questioned about symptoms of Tourette's syndrome and, if positive, be given a trial regimen of haloperidol; 2) some patients with compulsive exhibitionism and no symptoms of Tourette's syndrome have a genetic, neurochemical disorder and respond to haloperidol.

Sexual and other abnormalities in the family of a transsexual.

A case of transsexualism with homosexuality of Kinsey type 6 is described, in whose maternal kinship were found a large number of persons with various types of sexual abnormalities including one case of probable transsexualism. The pattern of intermarriage produces from generation to generation an increasing number of children with such abnormalities. The patient and a number of relatives also show epilepsy. That disorder seems to exist mainly in the paternal kinship, and the coexistence of transexxualism and epilepsy in the patient seems coincidental.