Neurobiological Underpinnings to Hypersexual Disorder

Study Overview
=================
Brief Summary
-----------------
Hypersexual Disorder (HD), sometimes called sexual addiction, is a disorder with intense sexual desires and psychological preoccupations that lead to out-of-control sexual activities with severe consequences. HD is related to higher risks of HIV infection and an important risk factor for committing sexual crimes. The prevalence of HD is 3-6% of the general population, thus, a significant burden for society. The neurobiological mechanisms behind HD are still unknown, and there is still a great need for causal treatments. This study is aimed at identifying neurobiological and psychological mechanisms underlying HD as a basis for treatment development. The overall goal is to improve mental health, quality of life, diagnosis and treatment options for affected individuals, and to reduce the impact HD can have on society. Patients with HD will be recruited at Karolinska University Hospital in close collaboration between endocrinologists, psychologists, psychiatrists, and brain researchers at Karolinska Institutet. Cases and healthy controls will undergo brain scans (MRI), psychological and blood tests to quantify neurobiological, cognitive, and behavioral aspects of HD. This study is directly integrated into clinical practice, can identify important targets for interventions and factors predicting treatment outcomes. This study is essential for a better understanding of HD, the improvement of treatments, and can have significant impact on the prevention of HIV infections and sexual crimes.

Official Title
-----------------
Neurobiologisk Bakgrund Till Hypersexuell Störning

Conditions
-----------------
Hypersexuality, Hypersexual Disorder, Compulsive Sexual Behavior

Intervention / Treatment
-----------------
* Other: Brain Imaging
* Other: Cognitive testing
* Other: Psychometric
* Other: Blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male At least 18 years of age, Fluent in the Swedish language Patients will meet diagnostic criteria for hypersexual disorder and will not have started with any psychotherapy or psychological treatment. Controls will be physically and psychologically healthy, and show no indication of clinical hypersexuality Exclusion Criteria: For both patients and controls any reported medical or clinical condition known to affect brain structure and function, test performance, or associated with risks for the MRI environment will be exclusionary. The investigators will exclude for the following: Severe neurological/psychiatric diseases or conditions (e.g., major depression, bipolar disorder, ADHD, autism, anxiety/panic disorder, obsessive compulsive disorder, personality disorder, Parkinson's disease, epilepsy, PTSD/chronic stress/burnout syndrom, Alzheimer's disease) Gender identity disorder/gender dysphoria Chronic pain conditions Impared vision, or other vision problems that cannot be corrected with MR-safe equipment. Hearing impairments, or problems with other senses History of severe brain damage/injuries Claustrophobia Having metal implants, a pacemaker, metallic braces or other MRI contra-indications Alcohol/drug dependence/abuse, eating disorder, pathological gambling, during the past 6 months. HIV and Hepatitis C/B, if the condition is untreated or virus levels detectable. Untreated endocrinologic diseases Medication: bensodiazepine, antipsychotics, mood stabilizers, centrally acting sympathicomimetics, SSRI (if use started less than 3 months ago). Any medication or pharmaceutical drug that interferes with sex hormone production or metabolism, i.e. ketoconazol, cyproteronacetate, spironolactone and similar drugs. Note: There is a potentially higher prevalence of comorbidities and medication use in patients. To facilitate recruitment and study completion, the investigators may include subjects that report specific conditions at the discretion of the principle investigator. In those cases, corresponding information will be recorded in order to control for potential confounders.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Controls (HC)<br>Controls will be physically and psychologically healthy and will show no indication of clinical hypersexuality. | Other: Brain Imaging<br>* Structural MRI (T1 weighted) Diffusion Tensor Imaging (DTI) resting state functional MRI (rs-fMRI) functional MRI (fMRI): Brain activity will be measured in response to sexual images (visually evoked sexual arousal; processing of sexual stimuli), and importantly during a phase when these stimuli are anticipated (neural correlates of wanting and desire; reward anticipation).<br>Other: Cognitive testing<br>* We will administer neuropsychological tests assessing objective measures for intelligence (Ravens Matrices) impulsivity and risk-taking behavior (Balloon Analogue Risk Task) inhibitory control (Stop Signal Task).<br>Other: Psychometric<br>* Administered questionnaires include anxiety and depression symptoms (MADRS, HADS, GAD), drug use (AUDIT, DUDIT), attention deficits (ASRS), impulsivity (BIS-11), reward seeking behavior (BIS/BAS), sexual orientation, (hyper)sexual behavior, desire and compulsivity aspects (HDSI, HBI, SCS, SDI, SIS/SES).<br>Other: Blood test<br>* Blood samples will be taken for routine health assessment, measurement of sex hormonal levels, HPA-axis function test (dexamethasone suppression), and potential DNA extraction and (epi)genetic profiling.<br>|
| Patients with hypersexual disorder (HD)<br>Patients will meet diagnostic criteria for HD as defined in the DSM-5 proposed criteria for hypersexual disorder (Kafka, 2010) and CSBD according to ICD-11. | Other: Brain Imaging<br>* Structural MRI (T1 weighted) Diffusion Tensor Imaging (DTI) resting state functional MRI (rs-fMRI) functional MRI (fMRI): Brain activity will be measured in response to sexual images (visually evoked sexual arousal; processing of sexual stimuli), and importantly during a phase when these stimuli are anticipated (neural correlates of wanting and desire; reward anticipation).<br>Other: Cognitive testing<br>* We will administer neuropsychological tests assessing objective measures for intelligence (Ravens Matrices) impulsivity and risk-taking behavior (Balloon Analogue Risk Task) inhibitory control (Stop Signal Task).<br>Other: Psychometric<br>* Administered questionnaires include anxiety and depression symptoms (MADRS, HADS, GAD), drug use (AUDIT, DUDIT), attention deficits (ASRS), impulsivity (BIS-11), reward seeking behavior (BIS/BAS), sexual orientation, (hyper)sexual behavior, desire and compulsivity aspects (HDSI, HBI, SCS, SDI, SIS/SES).<br>Other: Blood test<br>* Blood samples will be taken for routine health assessment, measurement of sex hormonal levels, HPA-axis function test (dexamethasone suppression), and potential DNA extraction and (epi)genetic profiling.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activity | Functional brain response (BOLD activity) upon presentation and anticipation of visual sexual stimuli. | acquired during brain imaging experiment (MRI scan day) | 
| Anatomical brain measures | Measures for brain morphology (regional cortical volume, thickness, surface area, and subcortical volumes) | Acquired during brain imaging experiment (MRI scan day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting state fMRI | Functional connectivity | Acquired during fMRI experiment (MRI scan day) | 
| Diffusion MRI | Structural connectivity | Acquired during fMRI experiment (MRI scan day) | 
| Reaction times | Response reaction times during fMRI task | Acquired during fMRI experiment (MRI scan day) | 
| Raven Progressive Matrices (cognitive task) | Objective measures for intelligence | Acquired at brain MRI assessment day, or as close to this day as possible. | 
| Balloon Analogue Risk Task (cognitive task) | Objective measures for impulsivity/risk-taking | Acquired at brain MRI assessment day, or as close to this day as possible. | 
| Stop Signal Task (cognitive task) | Objective measures for inhibitory control | Acquired at brain MRI assessment day, or as close to this day as possible. | 
| MADRS-S (questionnaire) | Montgomery Asberg Depression Rating Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| ASRS (questionnaire) | Adult ADHD Self-Report Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| AUDIT (questionnaire) | Alcohol Use Disorders Identification Test | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| DUDIT (questionnaire) | Drug Use Disorders Identification Test | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| EQ-5D (questionnaire) | General Health information | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| 4-item Kinsey-scale (questionnaire) | Sexual Orientation Dimension | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| HDSI (questionnaire) | Hypersexual Disorder Screening Inventory | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| SCS (questionnaire) | Sexual Compulsivity Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| HBI (questionnaire) | Hypersexual Behavior Inventory | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| SIS/SES (questionnaire) | Sexual Inhibition/Excitation Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| HADS (questionnaire) | Hospital Anxiety and Depression Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| GAD (questionnaire) | General Anxiety Disorder scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| BRSI-SE (questionnaire) | Bem Sex Role Inventory | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| RAADS (questionnaire) | Ritvo Autism Asperger Diagnostic Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| SDI (questionnaire) | Sexual Desire Inventory | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| BIS-11 (questionnaire) | Barratt Impulsiveness Scale | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| BIS/BAS (questionnaire) | Behavioral Inhibition/Activation System | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| Sexual Behavior (questionnaire) | Frequency of pornography consumption and sexual encounters. | Assessed through an online platform (as close to MRI scan day), and/or at MRI scan day | 
| fMRI experience rating (questionnaire) | Ratings of emotions experienced in context of the fMRI task, incl. craving/desire, stimuli induced sexual arousal. | Assessed right before and after MRI scan |