| 1. |
- 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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| 2. |
- Hallberg, Jonas, et al.
(författare)
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A Randomized Controlled Study of Group-Administered Cognitive Behavioral Therapy for Hypersexual Disorder in Men
- 2019
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 16:5, s. 733-745
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypersexual disorder (HD) is defined as a condition in which the individual loses control over engagement in sexual behaviors, leading to distress and negative effects on key life areas. Cognitive behavioral therapy (CBT) has been proven to reduce symptoms of hypersexual behavior; however, no randomized controlled study of CBT interventions for HD has been reported previously. Aim: To investigate the efficacy of group-administered CBT for HD. Methods: Male participants (n = 137) diagnosed with HD, were randomized between 7 weeks of group-administered CBT (n = 70) and a waitlist control receiving the intervention after 8 weeks (n = 67). Measurements were administered at pre-, mid-, and posttreatment, with follow-up after 3 and 6 months. Outcomes: The primary outcome was the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and secondary outcomes were the Sexual Compulsivity Scale (SCS) and measures of depression (Montgomery-Asberg Depression Rating Scale (MADRS-S), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), and treatment satisfaction (CSQ-8). Results: A significantly greater decrease in HD symptoms and sexual compulsivity, as well as significantly greater improvements in psychiatric well-being, were found for the treatment condition compared with the waitlist. These effects remained stable at 3 and 6 months after treatment. Clinical Implications: CBT can ameliorate HD symptoms and psychiatric distress, suggesting that the CBT program may serve as a first-line treatment in clinical settings. Strengths & Limitations: This is the first randomized controlled study evaluating the efficacy of a CBT programin a rather large sample of HD-specific diagnosed men. The long-termtreatment effects are vague due to the low response rate on follow-up measurements, and the efficacy of this program for hypersexual women remains unknown. Conclusion: This study supports the efficacy of a group-administered CBT program as a treatment option for HD; however, future studies should include women, comprise dismantling analysis of the constituting interventions, and evaluate other treatment formats, for example, administration via the Internet. Copyright (C) 2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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| 3. |
- Hallberg, Jonas, et al.
(författare)
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Internet-Administered Cognitive Behavioral Therapy for Hypersexual Disorder, With or Without Paraphilia(s) or Paraphilic Disorder(s) in Men : A Pilot Study
- 2020
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 17:10, s. 2039-2054
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Forskningsöversikt (refereegranskat)abstract
- Background: Hypersexual disorder (HD) is a condition in which the individual experiences loss of control over engagement in sexual behaviors, leading to negative effects on various areas of life. Paraphilias often present concomitantly with HD, and although cognitive behavioral therapy (CBT) has been proven to reduce engagement in hypersexual behavior, no studies have investigated the effects of Internet-administered CBT (ICBT) on HD, with or without paraphilia(s) or paraphilic disorder(s). Aim: To investigate the effects of Internet-administered CBT on HD, with or without paraphilia(s) or paraphilic disorder(s). Methods: Male participants (n = 36) evaluated positive according to the proposed diagnostic HD criteria, with or without paraphilia(s) or paraphilic disorder(s), received 12 weeks of ICBT. Measures were administered weekly over the treatment period, with an additional follow-up measurement 3 months after completion of treatment. An assessment interview was performed 2 weeks after treatment. Outcomes: The primary outcome was the Hypersexual Behavior Inventory (HBI-19), and secondary outcomes were the Hypersexual Disorder: Current Assessment Scale (HD:CAS), the Sexual Compulsivity Scale (SCS), as well as a tentative composite of 6 Severity Self-rating Measures, for Paraphilic Disorders and depression (Montgomery-Asberg Depression Rating Scale [MADRS-S]), psychological distress (Clinical Outcomes in Routine Evaluation Outcome Measure [CORE-OM]), and treatment satisfaction (CSQ-8). Results: Large, significant decreases in HD symptoms and sexual compulsivity were found, as well as moderate improvements in psychiatric well-being and paraphilic symptoms. These effects remained stable 3 months after treatment. Clinical Implications: ICBT can ameliorate HD symptoms, psychiatric distress, and paraphilic symptoms, which suggests that the ICBT for HD, with or without paraphilia(s) or paraphilic disorder(s), may constitute a valuable addition of treatment options in clinical settings. Strengths and Limitations: This is the first study evaluating the efficacy ofICBT on a sample of men suffering from HD. In addition, a proportion of the sample reported concomitant paraphilic interests and disorders, thus mirroring an everyday clinical practice in the field of sexual medicine. No control group was assigned, and some of the outcome measures are still to be validated. The long-term effects of ICBT and its efficacy in hypersexual women are unknown. Conclusions: This study gives support for ICBT as an effective treatment option for HD. Future evaluations of the treatment program should include women and larger samples in randomized controlled procedures and investigate the long-term effects. Copyright (C) 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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| 4. |
- Jokinen, Jussi, et al.
(författare)
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Methylation of HPA axis related genes in men with hypersexual disorder
- 2017
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Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 80, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor I (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48 bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. The methylation levels at the identified CRH site, cg23409074, were significantly correlated between blood and four different brain regions. CRH is an important integrator of neuroendocrine stress responses in the brain, with a key role in the addiction processes. Our results show epigenetic changes in the CRH gene related to hypersexual disorder in men.
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| 7. |
- Latth, Johanna, et al.
(författare)
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Effects of internet-delivered cognitive behavioral therapy on use of child sexual abuse material : A randomized placebo-controlled trial on the Darknet
- 2022
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The use of child sexual abuse material (CSAM) is an international public health and child protection challenge.Objective: To investigate whether Prevent It, a therapist-supported, internet-delivered, eight-week, cognitive behavioral therapy, reduces CSAM viewing among users.Methods: We conducted a global online single-blind (participants), parallel-group, superiority, randomized, psychological placebo-controlled trial with a one-month follow-up, 2019-2021 (ISRCTN76841676). We recruited anonymous participants, mainly from Darknet forums. Inclusion criteria: age 18+ years, past week CSAM use, and sufficient English language skills; exclusion criteria: severe psychiatric illness or non-serious intent to participate. The main outcome was change in self-reported, weekly viewing time from pre-to post-treatment, according to the Sexual Child Molestation Risk Assessment+.Results: A total of 160 participants (157 male, 2 non-binary, and 1 not reporting gender) from all world regions (age intervals [%]: 18-29 [49]; 30-39 [30]; 40-49 [15]; 50-59 [6]) were randomized (1:1) to Prevent It (N = 80) or Placebo (N = 80). Between-group, intention-to-treat analyses suggested a significantly larger decrease in viewing time in Prevent It participants vs. controls pre-to post-treatment (Prevent It: N = 76, Placebo: N = 78, estimate-0.25, 95 % CI,-0.46 to-0.04, p = .017, Cohen's d 0.18). Negative side effects from treatment were fewer in Prevent It compared to control participants and neither group reported severe adverse events.Conclusion: We provide initial support for the feasibility, efficacy, and safety of Prevent It to reduce CSAM viewing among motivated users. Further research is needed to validate these findings.
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