| 1. |
- Adebahr, Roberth, et al.
(författare)
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Reaching Men and Women at Risk of Committing Sexual Offences : Findings From the National Swedish Telephone Helpline PrevenTell
- 2021
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 18:9, s. 1571-1581
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2012 the Swedish Helpline project PrevenTell, targeting men and women with self-identified out-of-control and paraphilic sexual behavior, was launched by ANOVA, Karolinska University Hospital. The overall purpose was to reach the target group and via a telephone-contact encourage further on-site assessment and treatment.Aim: To describe men and women contacting PrevenTell during the first 7 years by delineate sexuality-related risk-factors for sexual violence, gender differences, and age-and gender-preferences when reporting a pedophilic interest.Method: A 52-item semi-structured telephone interview was conducted by experts in sexual medicine with individuals who contacted the helpline. The interview covered sociodemographic characteristics, problematic sexual behavior(s), and mental health and based on the information reported, interventions included recommending an appointment at ANOVA, supporting other appropriate healthcare, or motivation of individuals still ambivalent to treatment.Results: Data collection took place between March 2012 and October 2019. A total of 1573 respondents in the main target group (1454 men and 119 women) gave informed consent for participation. Compulsive sexual behavior was reported by 69% of respondents and 56% described at least one paraphilic interest. The prevalence of concomitant compulsive sexual behavior and a paraphilic interest was high, varying between 65% and 83%. Significant gender differences were found in socioeconomic and mental health variables, in which women showed fewer positive and stable life factors compared to men. A sexual preference for minors was reported by 24% of respondents. In this group, 63% reported use of child sexual exploitation material and 15% committed child sexual abuse. Respondents were offered anonymity, however 55% disclosed their identity and were enrolled for further assessment and treatment at ANOVA.Clinical Implications: The result of this study is of substantial relevance when developing secondary preventive initiatives targeting sexual violence in the community.Strengths and Limitations: This is the first study to present data from a national helpline targeting both men and women with a wide range of self-identified problematic sexual behaviors. Limitations include the lack of diagnostic confirmation on-site, hence, presented data provides only an indication of clinical conditions. Furthermore, the main objective of the interview was to motivate participants to seek further treatment, sometimes necessary to prioritize this over adherence to the semi-structured questionnaire, explaining the relatively high absence rate in some variables.Conclusion: Men and women at risk of committing sexual crimes can be reached through a national helpline service and motivated to undergo further assessment and treatment.
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| 2. |
- Boström, Adrian Desai E., et al.
(författare)
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HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration.MethodsThis study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.genetics.ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups.ResultsQuality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge – the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05).ConclusionEA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.
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| 3. |
- Boström, Adrian, et al.
(författare)
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Hypermethylation-associated downregulation of microRNA-4456 in hypersexual disorder with putative influence on oxytocin signalling : A DNA methylation analysis of miRNA genes
- 2020
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Ingår i: Epigenetics. - : Taylor & Francis. - 1559-2294 .- 1559-2308. ; 15:1-2, s. 145-160
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Tidskriftsartikel (refereegranskat)abstract
- Hypersexual disorder (HD) was proposed as a diagnosis in the DSM-5 and the classification ‘Compulsive Sexual Behavior Disorder’ is now presented as an impulse-control disorder in ICD-11. HD incorporates several pathophysiological mechanisms; including impulsivity, compulsivity, sexual desire dysregulation and sexual addiction. No previous study investigated HD in a methylation analysis limited to microRNA (miRNA) associated CpG-sites. The genome wide methylation pattern was measured in whole blood from 60 subjects with HD and 33 healthy volunteers using the Illumina EPIC BeadChip. 8,852 miRNA associated CpG-sites were investigated in multiple linear regression analyses of methylation M-values to a binary independent variable of disease state (HD or healthy volunteer), adjusting for optimally determined covariates. Expression levels of candidate miRNAs were investigated in the same individuals for differential expression analysis. Candidate methylation loci were further studied for an association with alcohol dependence in an independent cohort of 107 subjects. Two CpG-sites were borderline significant in HD – cg18222192 (MIR708)(p < 10E-05,pFDR = 5.81E-02) and cg01299774 (MIR4456)(p < 10E-06, pFDR = 5.81E-02). MIR4456 was significantly lower expressed in HD in both univariate (p < 0.0001) and multivariate (p < 0.05) analyses. Cg01299774 methylation levels were inversely correlated with expression levels of MIR4456 (p < 0.01) and were also differentially methylated in alcohol dependence (p = 0.026). Gene target prediction and pathway analysis revealed that MIR4456 putatively targets genes preferentially expressed in brain and that are involved in major neuronal molecular mechanisms thought to be relevant for HD, e.g., the oxytocin signalling pathway. In summary, our study implicates a potential contribution of MIR4456 in the pathophysiology of HD by putatively influencing oxytocin signalling.
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| 4. |
- Brokken, Leon, et al.
(författare)
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Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer.
- 2013
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 4:Feb.,14
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Tidskriftsartikel (refereegranskat)abstract
- In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped in genes encoding AHR and AHR repressor (AHRR). Binary logistic regression was used to calculate the risk of TGCC, non-seminoma versus seminoma, and metastasis versus localized disease. Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21-0.90; rs2672725: OR = 0.49, 95% CI: 0.25-0.94; rs6879758: OR = 0.27, 95% CI: 0.08-0.92; rs6896163: OR = 0.34, 95% CI: 0.12-0.98). This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action.
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| 5. |
- Brokken, Leon, et al.
(författare)
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Association of polymorphisms in genes encoding hormone receptors ESR1, ESR2 and LHCGR with the risk and clinical features of testicular germ cell cancer.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 351:2, s. 279-285
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Tidskriftsartikel (refereegranskat)abstract
- Testicular germ cell cancer (TGCC) is the most common malignancy in young men. Genetic variants known to be associated with risk of TGCC only partially account for the observed familial risks. We aimed to identify additional polymorphisms associated with risk as well as histological and clinical features of TGCC in 367 patients and 214 controls. Polymorphisms in ESR2 (rs1256063; OR=0.53, 95% CI: 0.35-0.79) and LHCGR (rs4597581; OR=0.68, 95% CI: 0.51-0.89, and rs4953617; OR=1.88, 95% CI: 1.21-2.94) associated with risk of TGCC. Polymorphisms in ESR1 (rs9397080; OR=1.85, 95% CI: 1.18-2.91) and LHCGR (rs7371084; OR=2.37, 95% CI: 1.26-4.49) associated with risk of seminoma and metastasis, respectively. SNPs in ESR1 (rs9397080) and LHCGR (rs7371084) were predictors of higher LH levels and higher androgen sensitivity index in healthy subjects. The results suggest that polymorphisms in ESR1, ESR2 and LHCGR contribute to the risk of developing TGCC, histological subtype, and risk to metastasis.
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| 6. |
- Chatzittofis, Andreas, et al.
(författare)
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CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters
- 2013
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 23:10, s. 1280-7
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin system and the hypothalamic-pituitary-adrenal (HPA) axis are involved in the biological vulnerability to suicidal behaviour. Altered levels of dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS have been reported in neuropsychiatric conditions. The aim of this study was to investigate CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA) and CSF and plasma levels of cortisol and DHEAS in 28 medication free suicide attempters and 19 healthy volunteers. Another aim was to investigate the relationship between neuroendocrine measures and childhood trauma in suicide attempters. As the study design includes a longitudinal part, we investigated whether CSF cortisol, 5-HIAA or DHEAS would predict subsequent suicide. We hypothesized higher cortisol levels in suicide attempters and lower CSF 5-HIAA levels and higher cortisol levels in suicide victims. Suicide attempters had higher CSF and plasma cortisol levels compared to healthy volunteers. Male suicide attempters had higher CSF DHEAS levels and female suicide attempters had lower CSF 5-HIAA levels compared to male and female healthy volunteers respectively. Exposure to interpersonal violence as a child showed a negative correlation with CSF cortisol/DHEAS ratio adjusted for age, gender and depression severity in a regression analysis. Suicide victims tended to have low CSF 5-HIAA and high CSF cortisol. Abused suicide victims had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. The results underlie the important role of the serotonergic system and HPA axis in suicidal behaviour and suggest that CSF DHEAS may be elevated in male suicide attempters.
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| 7. |
- Chatzittofis, Andreas, et al.
(författare)
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HPA axis dysregulation in men with hypersexual disorder
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 63, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5 mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels >= 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Asberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.
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| 8. |
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| 9. |
- Chatzittofis, Andreas, et al.
(författare)
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HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Chatzittofis, Andreas, et al.
(författare)
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Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men
- 2017
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Ingår i: Journal of Behavioral Addictions. - : Akademiai Kiado. - 2062-5871 .- 2063-5303. ; 6:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods: This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire-Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Asberg Depression Rating Scale - Self-rating. Results: Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion: Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion: Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.
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