From compulsivity to compulsion: the neural basis of compulsive disorders.

Compulsive behaviour, an apparently irrational perseveration in often maladaptive acts, is a potential transdiagnostic symptom of several neuropsychiatric disorders, including obsessive-compulsive disorder and addiction, and may reflect the severe manifestation of a dimensional trait termed compulsivity. In this Review, we examine the psychological basis of compulsions and compulsivity and their underlying neural circuitry using evidence from human neuroimaging and animal models. Several main elements of this circuitry are identified, focused on fronto-striatal systems implicated in goal-directed behaviour and habits. These systems include the orbitofrontal, prefrontal, anterior cingulate and insular cortices and their connections with the basal ganglia as well as sensoriomotor and parietal cortices and cerebellum. We also consider the implications for future classification of impulsive-compulsive disorders and their treatment.

The transition to compulsion in addiction.

Compulsion is a cardinal symptom of drug addiction (severe substance use disorder). However, compulsion is observed in only a small proportion of individuals who repeatedly seek and use addictive substances. Here, we integrate accounts of the neuropharmacological mechanisms that underlie the transition to compulsion with overarching learning theories, to outline how compulsion develops in addiction. Importantly, we emphasize the conceptual distinctions between compulsive drug-seeking behaviour and compulsive drug-taking behaviour (that is, use). In the latter, an individual cannot stop using a drug despite major negative consequences, possibly reflecting an imbalance in frontostriatal circuits that encode reward and aversion. By contrast, an individual may compulsively seek drugs (that is, persist in seeking drugs despite the negative consequences of doing so) when the neural systems that underlie habitual behaviour dominate goal-directed behavioural systems, and when executive control over this maladaptive behaviour is diminished. This distinction between different aspects of addiction may help to identify its neural substrates and new treatment strategies.

Beliefs, compulsive behavior and reduced confidence in control.

OCD has been conceptualized as a disorder arising from dysfunctional beliefs, such as overestimating threats or pathological doubts. Yet, how these beliefs lead to compulsions and obsessions remains unclear. Here, we develop a computational model to examine the specific beliefs that trigger and sustain compulsive behavior in a simple symptom-provoking scenario. Our results demonstrate that a single belief disturbance-a lack of confidence in the effectiveness of one's preventive (harm-avoiding) actions-can trigger and maintain compulsions and is directly linked to compulsion severity. This distrust can further explain a number of seemingly unrelated phenomena in OCD, including the role of not-just-right feelings, the link to intolerance to uncertainty, perfectionism, and overestimation of threat, and deficits in reversal and state learning. Our simulations shed new light on which underlying beliefs drive compulsive behavior and highlight the important role of perceived ability to exert control for OCD.

Development and Validation of the Metacognitions about Sex Scale: Exploring its Role as a Mediator between Negative Affect, Emotion Dysregulation Strategies, and Compulsive Sexual Behavior Disorder.

Metacognitions about sex are theorized to shape cognitive appraisal, coping mechanisms, and regulation or dysregulation before, during, and/or after exposure to sexual stimuli. In our study, we examined the construct structure and validity of the Metacognitions about Sex Scale (MSS) among a sample of adolescents. We estimated the convergent validity of the MSS by factors: negative affect, dysregulated thoughts, and impulsivity, and compulsive sexual behavior (CSB). We also ran a structural equation model in which we examined the possibility that metacognitions about sex would mediate the association between negative affect, dysregulated thoughts, and impulsivity on the one hand, and CSB on the other. The study population included 662 adolescents (252 boys and 410 girls, M = 16.70, SD = 1.32) between 13-18 years of age. The analyses indicated that the factorial structure of the MSS comprised the two expected factors. We also found that positive and negative metacognitions about sex significantly mediated the effect of negative affect, dysregulated thoughts, and impulsivity on CSB. The findings provide evidence that MSS among Israeli adolescents are psychometrically appropriate for use by researchers and practitioners in the prevention and treatment of CSB.

Stochastic synaptic plasticity underlying compulsion in a model of addiction.

Activation of the mesolimbic dopamine system reinforces goal-directed behaviours. With repetitive stimulation-for example, by chronic drug abuse-the reinforcement may become compulsive and intake continues even in the face of major negative consequences. Here we gave mice the opportunity to optogenetically self-stimulate dopaminergic neurons and observed that only a fraction of mice persevered if they had to endure an electric shock. Compulsive lever pressing was associated with an activity peak in the projection terminals from the orbitofrontal cortex (OFC) to the dorsal striatum. Although brief inhibition of OFC neurons temporarily relieved compulsive reinforcement, we found that transmission from the OFC to the striatum was permanently potentiated in persevering mice. To establish causality, we potentiated these synapses in vivo in mice that stopped optogenetic self-stimulation of dopamine neurons because of punishment; this led to compulsive lever pressing, whereas depotentiation in persevering mice had the converse effect. In summary, synaptic potentiation of transmission from the OFC to the dorsal striatum drives compulsive reinforcement, a defining symptom of addiction.

The Structure of Hypersexuality and Its Relation to Impulsivity.

Among the multiple controversies surrounding hypersexuality is the important issue of whether it constitutes a univocal construct. Although an initial study supported its homogeneity, more resent research has identified two separate subcomponents-problematic sexuality and sexual drive. The present survey study addressed this issue in a sample that included both in-person tested college students (n = 69) and online respondents (n = 339). A factor analysis of scales attempting to capture the indicators of each subcomponent of hypersexuality yielded two correlated, but separate factors. Whereas Problematic Sexuality (PS) comprised scales measuring sexual compulsivity, using sex as a coping mechanism, and the negative consequences of sexual behavior, Sexual Drive (SD) was defined by frequent sexual activity, preoccupation with sexual fantasies, a predilection for impersonal sexual behavior, and facile sexual arousal. These two subcomponents of hypersexuality were found to covary with different types of impulsivity, further supporting their discrimination and providing external validation for their differentiation. Contrary to a priori hypotheses, however, PS correlated highly with Callous/Manipulative/Risk-Taking as well as with a predicted Affective Instability/Behavioral Disinhibition factor, suggesting that PS may constitute an equifinality of separate developmental trajectories for those high on both subtypes of hypersexuality.

The Associations Between Attachment Insecurity and Compulsive Sexual Behavior Disorder or Problematic Pornography Use: The Mediating Role of Emotion Regulation Difficulties.

Compulsive sexual behavior disorder (CSBD) was previously considered an attachment disorder, while emotion dysregulation was thought to potentially be a key characteristic of it. However, this theoretical model was not tested in previous empirical research. In our cross-sectional study, we tested whether emotional regulation (ER) difficulties can be adopted as an explanatory mechanism for the relationships between attachment avoidance and anxiety, as well as CSBD and its most prevalent behavioral presentation-problematic pornography use (PPU). Participants (n = 1002; Mage = 50.49 years, SD = 13.32; men: 50.2%) completed an online survey regarding the investigated variables. In mediation analyses, attachment avoidance and anxiety were treated as simultaneous predictors, ER difficulties as a mediating variable, with CSBD/PPU severity as dependent variables. Emotion regulation difficulties and attachment anxiety had a direct positive effect on both CSBD and PPU. The direct effect of attachment avoidance on PPU was non-significant, and significant for CSBD depending on the measure used. Moreover, all the relationships between both insecure attachment dimensions and CSBD/PPU symptom severity were at least partially mediated by ER difficulties. Our results corroborate the theoretical claim that ER difficulties may be a useful framework for explaining the impact of attachment insecurity on CSBD/PPU. Theoretical and practical implications of the findings are discussed.

Exploring Compersion: A Study on Polish Consensually Non-Monogamous Individuals and Adaptation of the COMPERSe Questionnaire.

Compersion is a positive emotion experienced in relation to one's partner's relationship(s) with other partner(s). Experiencing it is highly desired in communities practicing consensual non-monogamy (CNM), especially polyamory. This article presents the results of a study on compersion on Polish CNM individuals. The main goal of the study was to adapt to the Polish-speaking population the COMPERSe (Classifying Our Metamour/Partner Emotional Response Scale; Flicker et al., 2021), the first standardized quantitative scale designed to measure compersion. The analyses were performed on data obtained from 211 individuals in CNM relationships and on a comparative group of 169 people in monogamous relationships. The results of the confirmatory factor analyses suggested that the three-factor model of the original COMPERSe version did not fit well, leading to further revisions that resulted in a 7-item, two-factor solution with excellent fit, excellent internal consistency, strong divergent and convergent validity, and excellent test-retest stability. The CNM individuals were found to have higher scores on compersion and cognitive empathy and were also less jealous than the monogamous participants. Furthermore, polyamorous individuals experienced more compersion and less aversion to partner's autonomy than people in open relationships. It was also revealed that compersion indirectly predicted relationship satisfaction by decreasing jealousy and that compersion was, in turn, predicted by cognitive empathy. However, when polyamorous and open relationships were analyzed separately, compersion predicted relationship satisfaction directly, but only in polyamorous relationships; meanwhile, in open relationships, satisfaction was directly predicted by cognitive empathy.

The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD). METHODS: We searched Pubmed, Scopus, Cochrane Library and PsychINFO databases until February 2023 for studies comparing patients with OCD and healthy controls on cognitive tests of compulsivity and impulsivity. The study followed PRISMA guidelines and was pre-registered on PROSPERO (CRD42021299017). RESULTS: Meta-analyses of 112 studies involving 8313 participants (4289 patients with OCD and 4024 healthy controls) identified significant impairments in compulsivity (g = -0.58, [95%CI -0.68, -0.47]; k = 76) and impulsivity (g = -0.48, [95%CI -0.57, -0.38]; k = 63); no significant difference between impairments. Medication use and comorbid psychiatric disorders were not significantly related to impairments. No associations were revealed with OCD severity, depression/anxiety, or illness duration. CONCLUSION: Cognitive phenotypes of compulsivity and impulsivity in patients with OCD appear to be orthogonal to clinical variables, including severity of OCD symptomatology. Their clinical impact is poorly understood and may require different clinical assessment tools and interventions.

Stress and compulsive buying-shopping disorder: A scoping review.

INTRODUCTION: Theoretical frameworks of behavioral addictions mostly acknowledge the role of stress in the development and maintenance of these disorders, models of compulsive buying-shopping disorder (CBSD) however rarely incorporated stress. The association between stress and CBSD has not been reviewed yet. METHODS: A scoping review was conducted to evaluate empirical results on the association between stress and CBSD. A comprehensive search string was employed in three databases. RESULTS: 16 studies were included. Correlative studies suggested significant correlations between general perceived stress and CBSD symptom severity. Studies involving mean comparisons found higher general perceived stress levels in persons with problematic buying-shopping behavior/CBSD compared to control participants (large effects). Mixed results were found in studies involving regression/structural equation models and ecological momentary assessments. One study with a stress/negative mood induction observed more CBSD symptoms in a high stress group compared to a low stress group. DISCUSSION: The studies are heterogeneous concerning design, samples and measures. Only very few studies surpass the level of cross-sectional correlative data which limits the ability to draw clear conclusions. Future research should study the impact of experimentally induced stress on CBSD symptoms, examine the relationship between stress and CBSD longitudinally and assess objective stress markers.

Disorders of compulsivity: Deficits in arbitrating learning strategies.

While previous research has shown that compulsivity is related to an imbalance between goal-directed and habitual learning systems, very little is known about whether this effect is due to the impairment of a single system or the impairment of the arbitration mechanism that determines which system controls behaviour at any given moment; the current study aims to address this disagreement. Nineteen alcohol use disorder, 30 obsessive-compulsive disorder (OCD) and 20 major depressive disorder patients and corresponding sex- and age-matched controls performed two-choice, three-stage Markov decision-making paradigm. Model-based and mode-free reinforcement learning models were used to independently fitted their behavioural data. Alcohol use disorder and OCD patients showed less model-based strategy choice than healthy controls in task conditions where the model-based strategy was optimal. Only OCD patients showed higher behavioural control system switching in task conditions where model-free use was optimal. Major depressive disorder patients did not differ from the matched control in both. These findings suggest that dysfunction in arbitration control between dual systems may be the basis for diverse disorders involving compulsivity.

Sense of agency and its disturbances: A systematic review targeting the intentional binding effect in neuropsychiatric disorders.

Sense of agency (SoA) indicates a person's ability to perceive her/his own motor acts as actually being her/his and, through them, to exert control over the course of external events. Disruptions in SoA may profoundly affect the individual's functioning, as observed in several neuropsychiatric disorders. This is the first article to systematically review studies that investigated intentional binding (IB), a quantitative proxy for SoA measurement, in neurological and psychiatric patients. Eligible were studies of IB involving patients with neurological and/or psychiatric disorders. We included 15 studies involving 692 individuals. Risk of bias was low throughout studies. Abnormally increased action-outcome binding was found in schizophrenia and in patients with Parkinson's disease taking dopaminergic medications or reporting impulsive-compulsive behaviors. A decreased IB effect was observed in Tourette's disorder and functional movement disorders, whereas increased action-outcome binding was found in patients with the cortico-basal syndrome. The extent of IB deviation from healthy control values correlated with the severity of symptoms in several disorders. Inconsistent effects were found for autism spectrum disorders, anorexia nervosa, and borderline personality disorder. Findings pave the way for treatments specifically targeting SoA in neuropsychiatric disorders where IB is altered.

Minority Stress, Psychological Distress, Sexual Compulsivity, and Avoidance-Based Motivations Associated with Methamphetamine Use Among Sexual Minority Men Living with HIV: Examining Direct and Indirect Associations Using Cross-Sectional Structural Equation Modeling.

OBJECTIVE: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g., HIV-related stigma) faced by SMM living with HIV and subsequent psychological and behavioral sequelae. We tested an integrated theoretical model comprised of pathways between stigma, discrimination, childhood sexual abuse, psychological distress, sexual compulsivity, and cognitive escape in predicting methamphetamine use among SMM living with HIV. METHODS: Among 423 SMM living with HIV, we tested a structural equation model examining factors hypothesized to be directly and indirectly associated with methamphetamine use. Analyses were adjusted for demographic covariates and sampling bias. RESULTS: The model showed good fit (CFI = 0.96, RMSEA = 0.01). Heterosexist discrimination was associated with psychological distress (ß = 0.39, p < 0.001) and psychological distress was associated with sexual compulsivity (ß = 0.33, p < 0.001). Sexual compulsivity was associated with cognitive escape (ß = 0.31, p < 0.001), which was associated with methamphetamine use (ß = 0.51, p < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape (ß = 0.05, p < 0.05). CONCLUSIONS: Heterosexist discrimination contributed to psychological distress among SMM living with HIV. Psychological distress is linked to methamphetamine use via sexual compulsivity and cognitive avoidance. Interventions seeking to reduce the likelihood that SMM living with HIV use methamphetamine should include coping strategies specific to heterosexism and related psychological distress.

The association between the coping attitudes and compulsive online buying behaviors of nurses.

AIM: The aim of this study is to examine the relationship between the coping attitudes and compulsive online buying behaviors of nurses. METHODS: This descriptive and correlational study was conducted with 253 nurses working in a research and training hospital in Istanbul between June and December 2022. Data were collected using a 'Participant Information Form', the 'Coping Attitudes Assessment Scale (R-COPE)', and the 'Compulsive Online Shopping Scale (COSS)'. Data were analyzed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression analysis. A p-value of <0.05 was considered statistically significant. RESULTS: The mean R-COPE score of the participants was 87.79 ± 10.40, and their mean COSS score was 26.00 ± 25.03. There was a negative and statistically significant correlation between the total R-COPE scores and the total COSS scores of the participants (p < 0.01). The coping attitudes (ß = -0.147) were a significant and negative predictor of compulsive online buying behaviors. Marital status (ß = 0.152), frequency of access to the internet (ß = 0.273), frequency of online shopping (ß = 0.365), and monthly amount of money spent for online shopping (ß = 0.123) were significant and positive predictors of compulsive online buying behaviors. These variables collectively explained 33 % (R2 = 0.328, p = 0.000) of the total variance in the compulsive online buying behaviors of the participants. CONCLUSION: Nurses had moderate levels of coping attitudes and low levels of compulsive online buying behaviors. Having low levels of coping attitudes, being single, accessing the internet frequently, doing online shopping frequently and spending a high amount of money for online shopping every month predicted the compulsive online buying behaviors.

Assessment of eating disorder symptoms, compulsive exercise, body dissatisfaction and depression in Swedish national team gymnasts, with a one-year follow-up.

PURPOSE: The purpose of this study was to explore changes in symptoms of eating disorders, compulsive exercise, and depression, between two assessments 12 months apart, among elite gymnasts. METHOD: Factors related to the development of mental health symptoms in male and female Swedish national team gymnasts were investigated using baseline and 1-year follow-up scores in two subscales of the Eating Disorders Inventory 3; drive for thinness and body dissatisfaction, two subscales of the Compulsive Exercise Test; avoidance and rule-driven behavior and exercise for weight control, and the Montgomery-Åsberg Depression Rating Scale-Self report (MADRS-S). Linear mixed models were used to investigate the influence of drive for thinness, exercise for weight control, avoidance and rule-driven behavior, and MADRS-S on body dissatisfaction. RESULTS: Body dissatisfaction increased from baseline to the follow-up assessment, while drive for thinness and depression remained stable. Symptoms of eating disorders and depression were generally low in this group of elite gymnasts at both assessments. Drive for thinness, exercise for weight control, and symptoms of depression were associated with body dissatisfaction. DISCUSSION: Our findings indicate that there were no significant changes over time in eating disorders and depression symptoms but significant associations with body dissatisfaction. Furthermore, we found independent effects of drive for thinness, exercise for weight control and symptoms of depression for body dissatisfaction.

[Compulsive Sexual Behaviour Disorder and Sexual Motivations]. / A kompulzív szexuális viselkedési zavar és a szexuális motivációk összefüggései.

INTRODUCTION: Compulsive sexual behaviour or hypersexuality has been the subject of growing interest among academic circles. However, relatively few reliable predictors have been identified. The aim of the present study was to examine whether different types of sexual motivations based on Self-Determination Theory can account for compulsive sexual behaviour. METHOD: The study was conducted on a non-clinical sample of nearly 1000 participants. Sexual motivation was assessed using the Sexual Motivation Scale and compulsive sexual behaviour was assessed using the Hypersexual Behaviour Inventory. Both measures showed adequate reliability. Multiple linear regression was performed to analyse the relationship between the variables. RESULTS: In the regression, controlling for gender, of the six motivational factors, integrated (ß = 0.167), introjected (ß = 0.074) and amotivation (ß = 0.128) were found significant (p <0.001), and identified was nearly significant (ß = 0.53; p = 0.065). The intrinsic (ß = -0.032; p = 0.366) and extrinsic (ß = -0.027; p = 0.168) forms of motivation had no impact on hypersexuality. The total explained variance of the model was 18% (p <0.001). Results indicated that three of the six motivational factors positively and weakly predicted hypersexuality. CONCLUSION: The original hypothesis of the study, that less self-determined motivated sexual behaviour would be a better predictor of compulsive sexual behaviour, was not confirmed. In practice, positively related variables, especially amotivation, may play an important role in psychotherapeutic processes. However, in order to better understand compulsive sexual behaviour, additional factors still need to be explored.

Mapping the neuroanatomical abnormalities in a phenotype of male compulsive rats.

Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI). Voxel-based morphometry of segmented MRI images revealed larger white matter volumes in anterior commissure and corpus callosum of HD rats compared with LD rats. HD rats also showed significantly larger regional volumes of dorsolateral orbitofrontal cortex, striatum, amygdala, hippocampus, midbrain, sub-thalamic nucleus, and cerebellum. By contrast, the medial prefrontal cortex was significantly smaller in HD rats compared with LD rats with no significant group differences in whole brain, ventricular, or cerebrospinal fluid volumes. These findings show that limbic cortico-basal ganglia structures implicated in impulse control disorders are distinct in rats that are vulnerable to develop compulsive behavior. Such abnormalities may be relevant to the etiology of compulsive disorders in humans.

Confirming and Expanding the Moral Incongruence Model of Compulsive Sexual Behavior.

Compulsive sexual behavior (CSB) is a clinical syndrome in which repetitive sexual behaviors, urges, or thoughts cause significant distress and impairment. Moral incongruence (MI), or conflict between an individual's sexual behaviors and moral beliefs, is highly associated with self-reported problematic pornography use, a common behavioral manifestation of CSB. However, it is currently unknown whether MI is associated with other self-reported compulsive sexual behaviors, such as masturbation, sexual fantasy, and sex with multiple partners. Additionally, research on MI has not explored whether emotional responses to sexual cues (i.e., erotophilia-erotophobia) may serve as a moderating variable in the MI model. To address these gaps in the literature, this study administered an online survey to a sample of 804 American participants. Results confirmed previous research on MI indicating frequency of pornography use is more strongly associated with self-reported CSB at high levels of moral disapproval. This moderation was also replicated with frequency of sexual fantasy and number of sex partners, but not with frequency of masturbation. Results also indicated that self-reported CSB was modestly associated with positive emotional response to sexual cues (i.e., erotophilia) but offered limited support for erotophilia as a moderator in the MI model. Collectively, these findings suggest the MI model can be expanded to several behavioral manifestations of CSB, but that emotional responses to sexual cues may play a limited or more nuanced role in MI.

The Structure of Compulsive Sexual Behavior: A Network Analysis Study.

Compulsive sexual behavior is a phenomenon characterized by a persistent failure to control intense, repetitive sexual impulses or urges, resulting in repetitive sexual behavior that causes marked distress or impairment in personal, familial, social, educational, or occupational areas of functioning. Despite its major impact on mental health and quality of life, little is known about its internal structure and whether this phenomenon differs across genders, age groups, and risk status. By considering a large online sample (n = 3186; 68.3% males), ranging from 14 to 64 years old, compulsive sexual behavior was explored by means of network analysis. State-of-the-art analytical techniques were adopted to investigate the pattern of association among the different elements of compulsive sexual behavior, identify possible communities of nodes, pinpoint the most central nodes, and detect differences between males and females, among different age groups, as well as between individuals at low and high risk of developing a full-blown disorder. The analyses revealed that the network was characterized by three communities, namely Consequence, Preoccupation, and Perceived Dyscontrol, and that the most central node was related to (perceived) impulse dyscontrol. No substantial differences were found between males and females and across age. Failing to meet one's own commitments and responsibilities was more central in individuals at high risk of developing a full-blown disorder than in those at low risk.

Conradi-Hünerman-Happle Syndrome and Obsessive-Compulsive Disorder: a clinical case report.

BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a common and chronic psychiatric disorder with significant morbidity characterized by intrusive, uncontrollable and reoccurring thoughts (i.e., obsessions) and/or ritualistic behaviours (i.e., compulsions). Conradi-Hünerman-Happle Syndrome (CHHS) is a rare inherited X-linked dominant variant of chondrodysplasia punctata, a heterogeneous group of rare bone dysplasias characterized by punctate epiphyseal calcifications of complex etiology and pathophysiology that remain to be defined. Available literature reveals a lacuna in regards to the coexistence of the entities with no clinical reports described. CASE PRESENTATION: A 12 year old female patient with diagnosis of CHHS, presents to psychiatric consultation due to aggravation of her OCD clinical picture, with aggravation of hand-washing frequency during the Covid-19 pandemic with significant functional impact. Psychopharmacological treatment aimed at OCD with Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic was instituted with favourable, albeit partial response. CONCLUSIONS: The authors aim to describe a clinical case in which the patient presents with Conradi-Hünerman-Happle Syndrome and Obsessive-Compulsive Disorder. Clinical descriptions of CHHS and OCD are not available in the literature. Through this case description the authors aim to present a rare case as well as discuss an eventual association between etiology and/or pathophysiology of the two disorders.