Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men

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–Åsberg 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

Impulsivity in Compulsive Sexual Behavior Disorder and Pedophilic Disorder

Background and aims: Impulsivity is regarded as a risk factor for sexual crime reoffending, and a suggested core feature in Compulsive Sexual Behavior Disorder. The aim of this study was to explore clinical (e.g. neurodevelopmental disorders), behavioral and neurocognitive dimensions of impulsivity in disorders of problematic sexuality, and the possible correlation between sexual compulsivity and impulsivity. Methods: Men with Compulsive Sexual Behavior Disorder (n = 20), and Pedophilic Disorder (n = 55), enrolled in two separate drug trials in a specialized Swedish sexual medicine outpatient clinic, as well as healthy male controls (n = 57) were assessed with the Hypersexual Behavior Inventory (HBI) for sexual compulsivity, and with the Barratt Impulsiveness Scale (BIS) and Connors' Continuous Performance Test-II (CPT-II) for impulsivity. Psychiatric comorbidity information was extracted from interviews and patient case files. Results: Approximately a quarter of the clinical groups had Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder. Both clinical groups reported more compulsive sexuality (r = 0.73-0.75) and attentional impulsivity (r = 0.36-0.38) than controls (P < 0.05). Based on results on univariate correlation analysis, BIS attentional score, ADHD, and Commissions T-score from CPT-II were entered in a multiple linear regression model, which accounted for 15% of the variance in HBI score (P < 0.0001). BIS attentional score was the only independent positive predictor of HBI (P = 0.001). Discussion: Self-rated attentional impulsivity is an important associated factor of compulsive sexuality, even after controlling for ADHD. Psychiatric comorbidity and compulsive sexuality are common in Pedophilic Disorder. Conclusion: Neurodevelopmental disorders and attentional impulsivity - including suitable interventions - should be further investigated in both disorders

A randomised controlled trial of fluoxetine versus naltrexone in compulsive sexual behaviour disorder : presentation of the study protocol

Background: Compulsive sexual behaviour disorder is a new disorder in the International Classification of Diseases (ICD-11), and is associated with negative consequences in different areas of life. Evidence for pharmacological treatment of compulsive sexual behaviour disorder is weak and treatment options are limited. This proposed study will be the largest and the first randomised controlled trial comparing the efficacy and tolerability of two active drugs in compulsive sexual behaviour disorder. Methods and analysis: Eighty adult participants with compulsive sexual behaviour disorder according to ICD-11 will be randomised to receive either naltrexone 25-50 mg or fluoxetine 20-40 mg for 8 weeks, followed by 6 weeks without treatment. The study will be conducted in a subspecialised outpatient sexual medicine unit at Karolinska University Hospital, Stockholm, Sweden. The study is financed by grants and entirely independent of the manufacturers. Exclusion criteria include severe psychiatric or psychical illness, changes to concurrent medication and non-compatible factors contraindicating the use of either drug. The primary outcome measure is the Hypersexual Disorder: Current Assessment Scale (HD: CAS), and tolerability will be assessed by the Udvalg for Kliniske Undersogelser side effect rating scale (UKU), drug accountability, adherence to treatment and drop-out rate. Participants will complete questionnaires at regular intervals, with the main endpoint for efficacy after 8 weeks (end of treatment) and after 14 weeks (follow-up). Blood chemistry will be repeatedly collected as a safety precaution and for research purposes. The results will be analysed using an appropriate analysis of variance model or a mixed model, depending on the distribution of HD: CAS and the extent of missing data

Structural brain differences related to compulsive sexual behavior disorder

Background and aims: Compulsive sexual behavior disorder (CSBD) has been included as an impulse control disorder in the International Classification of Diseases (ICD-11). However, the neurobiological mechanisms underlying CSBD remain largely unknown, and given previous indications of addiction-like mechanisms at play, the aim of the present study was to investigate if CSBD is associated with structural brain differences in regions involved in reward processing. Methods: We analyzed structural MRI data of 22 male CSBD patients (mean = 38.7 years, SD = 11.7) and 20 matched healthy controls (HC; mean = 37.6 years, SD = 8.5). Main outcome measures were regional cortical thickness and surface area. We also tested for case-control differences in subcortical structures and the effects of demographic and clinical variables, such as CSBD symptom severity, on neuroimaging outcomes. Moreover, we explored case-control differences in regions outside our hypothesis including white matter. Results: CSBD patients had significantly lower cortical surface area in right posterior cingulate cortex than HC. We found negative correlations between right posterior cingulate area and CSBD symptoms scores. There were no group differences in subcortical volume. Conclusions: Our findings suggest that CSBD is associated with structural brain differences, which contributes to a better understanding of CSBD and encourages further clarifications of the neurobiological mechanisms underlying the disorder

Neurochemical and Hormonal Contributors to Compulsive Sexual Behavior Disorder

Purpose of Review: Compulsive sexual behavior disorder has been recently included in the 11th revision of the International Classification of Diseases (ICD-11), and the possible contribution of neurochemical and hormonal factors have been reported. However, relatively little is known concerning the neurobiology underlying this disorder. The aim of this article is to review and discuss published findings in the area. Recent Findings: Evidence suggests that the neuroendocrine systems are involved in the pathophysiology of compulsive sexual behavior. The hypothalamus-pituitary adrenal axis, the hypothalamus-pituitary–gonadal axis, and the oxytocinergic system have been implicated. Summary: Further studies are needed to elucidate the exact involvement of neuroendocrine and hormonal systems in compulsive sexual behavior disorder. Prospective longitudinal studies are particularly needed, especially those considering co-occurring psychiatric disorders and obtaining hormonal assessments in experimental circumstances with appropriate control groups

High plasma oxytocin levels in men with hypersexual disorder

Context: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior. Objective: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol. Design: Longitudinal. Setting: ANOVA clinic (Karolinska University Hospital). Patients or other participants: 64 males with HD and 38 age-matched healthy volunteers. Main Outcome Measures: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms. Interventions: A patient subgroup (n=30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured. Results: Hypersexual men (n=64) exhibited significantly higher oxytocin plasma levels (mean±SD: 31.0±9.9 pM) compared with healthy volunteers (16.9±3.9 pM; P<0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n=30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5±10.1 pM) to posttreatment (20.2±8.0 pM; P<0.001). Conclusions: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress

Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder

Introduction: Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis. Aim: The aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels. Methods: Basal morning plasma levels of testosterone, LH, and sex hormone-binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-Asberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis-coupled genes were included. Main Outcome Measures: Testosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis-coupled CpG sites with testosterone and LH levels. Results: LH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis-coupled genes and plasma testosterone or LH levels after multiple testing corrections. Conclusions: Subtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men

Neural and behavioral correlates of sexual stimuli anticipation point to addiction-like mechanisms in compulsive sexual behavior disorder

Background and aims: Compulsive sexual behavior disorder (CSBD) is characterized by persistent patterns of failure to control sexual impulses resulting in repetitive sexual behavior, pursued despite adverse consequences. Despite previous indications of addiction-like mechanisms and the recent impulse-control disorder classification in the International Classification of Diseases (ICD-11), the neurobiological processes underlying CSBD are unknown. Methods: We designed and applied a behavioral paradigm aimed at disentangling processes related to anticipation and viewing of erotic stimuli. In 22 male CSBD patients (age: M = 38.7, SD = 11.7) and 20 healthy male controls (HC, age: M = 37.6, SD = 8.5), we measured behavioral responses and neural activity during functional magnetic resonance imaging (fMRI). The main outcomes were response time differences between erotic and non-erotic trials and ventral striatum (VS) activity during anticipation of visual stimuli. We related these outcomes with each other, to CSBD diagnosis, and symptom severity. Results: We found robust case-control differences on behavioral level, where CSBD patients showed larger response time differences between erotic and non-erotic trials than HC. The task induced reliable main activations within each group. While we did not observe significant group differences in VS activity, VS activity during anticipation correlated with response time differences and self-ratings for anticipation of erotic stimuli. Discussion and Conclusions: Our results support the validity and applicability of the developed task and suggest that CSBD is associated with altered behavioral correlates of anticipation, which were associated with ventral striatum activity during anticipation of erotic stimuli. This supports the idea that addiction-like mechanisms play a role in CSBD

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