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.

Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system.

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.

Maximizing translational value in models of compulsive behavior: A commentary on Pickenhan et al. (2024).

In this issue of Cognitive, Affective, and Behavioral Neuroscience, Pickenhan et al. (2024) discuss the need for translational studies to understand features underlying obsessive-compulsive disorder (OCD). They highlight the translational value of the observing-response task (ORT) for modeling functional and maladaptive checking behaviors, a common symptom of OCD.

Opening new vistas on obsessive-compulsive disorder with the observing response task.

Obsessive-compulsive disorder (OCD), a highly prevalent and debilitating disorder, is incompletely understood in terms of underpinning behavioural, psychological, and neural mechanisms. This is attributable to high symptomatic heterogeneity; cardinal features comprise obsessions and compulsions, including clinical subcategories. While obsessive and intrusive thoughts are arguably unique to humans, dysfunctional behaviours analogous to those seen in clinical OCD have been examined in nonhuman animals. Genetic, ethological, pharmacological, and neurobehavioural approaches all contribute to understanding the emergence and persistence of compulsive behaviour. One behaviour of particular interest is maladaptive checking, whereby human patients excessively perform checking rituals despite these serving no purpose. Dysfunctional and excessive checking is the most common symptom associated with OCD and can be readily operationalised in rodents. This review considers animal models of OCD, the neural circuitries associated with impairments in habit-based and goal-directed behaviour, and how these may link to the compulsions observed in OCD. We further review the Observing Response Task (ORT), an appetitive instrumental learning procedure that distinguishes between functional and dysfunctional checking, with translational application in humans and rodents. By shedding light on the psychological and neural bases of compulsive-like checking, the ORT has potential to offer translational insights into the underlying mechanisms of OCD, in addition to being a platform for testing psychological and neurochemical treatment approaches.

Disentangling associations between impulsivity, compulsivity, and performance monitoring.

Disorders marked by high levels of impulsivity and compulsivity have been linked to changes in performance monitoring, specifically the error-related negativity (ERN). We investigated the relationship between performance monitoring and individual differences in impulsivity and compulsivity. A total of 142 participants were recruited into four groups, each with different combinations of impulsivity and compulsivity, and they performed a flanker task to assess error-related brain activity. We defined error-related brain activity as ERN amplitude and theta power. Single-trial regression was employed to analyze the amplitude differences between incorrect and correct trials within the ERN time window. The findings revealed that impulsivity, compulsivity, and different measures of response processing exhibited distinct interactions, which were influenced by the configuration of impulsivity and compulsivity, but also depended on the measure of response processing. Specifically, high compulsivity predicted larger ERN amplitudes in individuals with low impulsivity, whereas high impulsivity had no significant effect on ERN amplitude in individuals with low compulsivity. Furthermore, when both impulsivity and compulsivity were high, no significant increase in ERN amplitude was observed; instead, there was a reduced difference between incorrect and correct trials. No significant differences were found for theta power. While the association between error-related brain activity and transdiagnostic markers or psychopathology may be smaller than generally assumed, considering the interaction between different transdiagnostic markers and their facets can enhance our understanding of the complex associations that arise during the investigation of neural correlates of performance monitoring, specifically the ERN.

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.

Compulsivity is linked to reduced adolescent development of goal-directed control and frontostriatal functional connectivity.

A characteristic of adaptive behavior is its goal-directed nature. An ability to act in a goal-directed manner is progressively refined during development, but this refinement can be impacted by the emergence of psychiatric disorders. Disorders of compulsivity have been framed computationally as a deficit in model-based control, and have been linked also to abnormal frontostriatal connectivity. However, the developmental trajectory of model-based control, including an interplay between its maturation and an emergence of compulsivity, has not been characterized. Availing of a large sample of healthy adolescents (n = 569) aged 14 to 24 y, we show behaviorally that over the course of adolescence there is a within-person increase in model-based control, and this is more pronounced in younger participants. Using a bivariate latent change score model, we provide evidence that the presence of higher compulsivity traits is associated with an atypical profile of this developmental maturation in model-based control. Resting-state fMRI data from a subset of the behaviorally assessed subjects (n = 230) revealed that compulsivity is associated with a less pronounced change of within-subject developmental remodeling of functional connectivity, specifically between the striatum and a frontoparietal network. Thus, in an otherwise clinically healthy population sample, in early development, individual differences in compulsivity are linked to the developmental trajectory of model-based control and a remodeling of frontostriatal connectivity.

Model-Based Planning Deficits in Compulsivity Are Linked to Faulty Neural Representations of Task Structure.

Compulsive individuals have deficits in model-based planning, but the mechanisms that drive this have not been established. We examined two candidates-that compulsivity is linked to (1) an impaired model of the task environment and/or (2) an inability to engage cognitive control when making choices. To test this, 192 participants performed a two-step reinforcement learning task with concurrent EEG recordings, and we related the neural and behavioral data to their scores on a self-reported transdiagnostic dimension of compulsivity. To examine subjects' internal model of the task, we used established behavioral and neural responses to unexpected events [reaction time (RT) slowing, P300 wave, and parietal-occipital alpha band power] measured when an unexpected transition occurred. To assess cognitive control, we probed theta power at the time of initial choice. As expected, model-based planning was linked to greater behavioral (RT) and neural (alpha power, but not P300) sensitivity to rare transitions. Critically, the sensitivities of both RT and alpha to task structure were weaker in those high in compulsivity. This RT-compulsivity effect was tested and replicated in an independent pre-existing dataset (N = 1413). We also found that mid-frontal theta power at the time of choice was reduced in highly compulsive individuals though its relation to model-based planning was less pronounced. These data suggest that model-based planning deficits in compulsive individuals may arise, at least in part, from having an impaired representation of the environment, specifically how actions lead to future states.SIGNIFICANCE STATEMENT Compulsivity is linked to poorer performance on tasks that require model-based planning, but it is unclear what precise mechanisms underlie this deficit. Do compulsive individuals fail to engage cognitive control at the time of choice? Or do they have difficulty in building and maintaining an accurate representation of their environment, the foundation needed to behave in a goal-directed manner? With reaction time and EEG measures in 192 individuals who performed a two-step decision-making task, we found that compulsive individuals are less sensitive to surprising action-state transitions, where they slow down less and show less alpha band suppression following a rare transition. These findings implicate failures in maintaining an accurate model of the world in model-based planning deficits in compulsivity.

Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals.

Substance use disorders (SUDs) impose severe negative impacts upon individuals, their families, and society. Clinical studies demonstrate that some chronic stimulant users are able to curtail their drug use when faced with adverse consequences while others continue to compulsively use drugs. The mechanisms underlying this dichotomy are poorly understood, which hampers the development of effective individualized treatments of a disorder that currently has no Food and Drug Administration-approved pharmacological treatments. In the present study, using a rat model of methamphetamine self-administration (SA) in the presence of concomitant foot shocks, thought to parallel compulsive drug taking by humans, we found that SA behavior correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal "go" circuit and a decreased prelimbic cortex-ventrolateral striatal "stop" circuit. Critically, this correlation was seen only in rats who continued to self-administer at a relatively high rate despite receiving foot shocks of increasing intensity. While the stop circuit functional connectivity became negative after repeated SA in all rats, "shock-resistant" rats showed strengthening of this negative connectivity after shock exposure. In contrast, "shock-sensitive" rats showed a return toward their baseline levels after shock exposure. These results may help guide novel noninvasive brain stimulation therapies aimed at restoring the physiological balance between stop and go circuits in SUDs.

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective.

Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top-down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug-induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico-striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug-motivated behaviours that might explain individual risk for addiction.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease.

BACKGROUND: The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson's disease (PD) are understudied. OBJECTIVE: To investigate clinical predictors of STN-DBS effects on ICB. METHODS: In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into 'QUIP-RS improvement or worsening' and analysed between-group differences. RESULTS: We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the 'QUIP-RS worsening' group had more severe baseline impairment in the NMSS attention/memory domain. CONCLUSIONS: Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS. TRIAL REGISTRATION NUMBER: DRKS00006735.

Individual differences in the engagement of habitual control over alcohol seeking predict the development of compulsive alcohol seeking and drinking.

Excessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol-preferring rats were pre-exposed intermittently to a two-bottle choice procedure and trained on a seeking-taking chained schedule of alcohol reinforcement until some individuals developed punishment-resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome-devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome devaluation (were more habitual) were more likely to show punishment-resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals who have preferentially engaged the habit system.

Compulsive Alcohol Seeking Results from a Failure to Disengage Dorsolateral Striatal Control over Behavior.

The acquisition of drug, including alcohol, use is associated with activation of the mesolimbic dopamine system. However, over the course of drug exposure the control over drug seeking progressively devolves to anterior dorsal striatum (aDLS) dopamine-dependent mechanisms. The causal importance of this functional recruitment of aDLS in the switch from controlled to compulsive drug use in vulnerable individuals remains to be established. Here we tested the hypothesis that individual differences in the susceptibility to aDLS dopamine-dependent control over alcohol seeking predicts and underlies the development of compulsive alcohol seeking. Male alcohol-preferring rats, the alcohol-preferring phenotype of which was confirmed in an intermittent two-bottle choice procedure, were implanted bilaterally with cannulae above the aDLS and trained instrumentally on a seeking-taking chained schedule of alcohol reinforcement until some individuals developed compulsive seeking behavior. The susceptibility to aDLS dopamine control over behavior was investigated before and after the development of compulsivity by measuring the extent to which bilateral aDLS infusions of the dopamine receptor antagonist α-flupenthixol (0, 5, 10, and 15 µg/side) decreased alcohol seeking at different stages of training, as follows: (1) after acquisition of instrumental taking responses for alcohol; (2) after alcohol-seeking behavior was well established; and (3) after the development of punishment-resistant alcohol seeking. Only alcohol-seeking, not alcohol-taking, responses became dependent on aDLS dopamine. Further, marked individual differences in the susceptibility of alcohol seeking to aDLS dopamine receptor blockade actually predicted the vulnerability to develop compulsive alcohol seeking, but only in subjects dependent on aDLS dopamine-dependent control.SIGNIFICANCE STATEMENT Over the course of addictive drug exposure, there is a transition in the control over drug seeking from ventral to anterior dorsal striatum (aDLS) dopamine-dependent mechanisms, but it is unclear whether this is causally involved in the development of compulsive drug seeking. We tested the hypothesis that individual differences in the reliance of alcohol seeking on aDLS dopamine predicts and underlies the emergence of compulsive alcohol seeking. We identified individual differences in the reliance of well established alcohol seeking, but not taking behavior, on aDLS mechanisms and also showed that this predicted the subsequent development of compulsive alcohol-seeking behavior. Thus, those individuals in whom alcohol seeking depended on aDLS mechanisms were vulnerable subsequently to display compulsivity.

Strengthened Inputs from Secondary Motor Cortex to Striatum in a Mouse Model of Compulsive Behavior.

Hyperactivity in striatum is associated with compulsive behaviors in obsessive-compulsive disorder (OCD) and related illnesses, but it is unclear whether this hyperactivity is due to intrinsic striatal dysfunction or abnormalities in corticostriatal inputs. Understanding the cellular and circuit properties underlying striatal hyperactivity could help inform the optimization of targeted stimulation treatments for compulsive behavior disorders. To investigate the cellular and synaptic abnormalities that may underlie corticostriatal dysfunction relevant to OCD, we used the Sapap3 knock-out (Sapap3-KO) mouse model of compulsive behaviors, which also exhibits hyperactivity in central striatum. Ex vivo electrophysiology in double-transgenic mice was used to assess intrinsic excitability and functional synaptic input in spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in central striatum of Sapap3-KOs and wild-type (WT) littermates. While we found no differences in intrinsic excitability of SPNs or FSIs between Sapap3-KOs and WTs, excitatory drive to FSIs was significantly increased in KOs. Contrary to predictions, lateral orbitofrontal cortex-striatal synapses were not responsible for this increased drive; optogenetic stimulation revealed that lateral orbitofrontal cortex input to SPNs was reduced in KOs (∼3-fold) and unchanged in FSIs. However, secondary motor area (M2) postsynaptic responses in central striatum were significantly increased (∼6-fold) in strength and reliability in KOs relative to WTs. These results suggest that increased M2-striatal drive may contribute to both in vivo striatal hyperactivity and compulsive behaviors, and support a potential role for presupplementary/supplementary motor cortical regions in the pathology and treatment of compulsive behavior disorders.SIGNIFICANCE STATEMENT These findings highlight an unexpected contribution of M2 projections to striatal dysfunction in the Sapap3-KO obsessive-compulsive disorder (OCD)-relevant mouse model, with M2 inputs strengthened by at least sixfold onto both spiny projection neurons and fast-spiking interneurons in central striatum. Because M2 is thought to be homologous to presupplementary/supplementary motor areas (pre-SMA/SMA) in humans, regions important for movement preparation and behavioral sequencing, these data are consistent with a model in which increased drive from M2 leads to excessive selection of sequenced motor patterns. Together with observations of hyperactivity in pre-SMA/SMA in both OCD and Tourette syndrome, and evidence that pre-SMA is a potential target for repetitive transcranial magnetic stimulation treatment in OCD, these results support further dissection of the role of M2 in compulsivity.

Perineuronal nets in the insula regulate aversion-resistant alcohol drinking.

One of the most pernicious characteristics of alcohol use disorder is the compulsion to drink despite negative consequences. The insular cortex controls decision making under conditions of risk or conflict. Cortical activity is tightly controlled by inhibitory interneurons that are often enclosed by specialized extracellular matrix structures known as perineuronal nets (PNNs), which regulate neuronal excitability and plasticity. The density of PNNs in the insula increases after repeated bouts of binge drinking, suggesting that they may play a role in the transition from social to compulsive, or aversion-resistant, drinking. Here, we investigated whether insular PNNs play a role in aversion-resistant alcohol drinking using a mouse model in which ethanol was adulterated with the bitter tastant quinine. Disrupting PNNs in the insula rendered mice more sensitive to quinine-adulterated ethanol but not ethanol alone. Activation of the insula, as measured by c-fos expression, occurred during aversion-resistant drinking and was further enhanced by elimination of PNNs. These results demonstrate that PNNs control the activation of the insula during aversion-resistant drinking and suggest that proper excitatory/inhibitory balance is important for decision making under conditions of conflict. Disrupting PNNs in the insula or optimizing insula activation may be a novel strategy to reduce aversion-resistant drinking.

Effects of glutamate-related drugs on anxiety and compulsive behavior in rats with obsessive-compulsive disorder.

Objective: Altered glutamatergic neurotransmission has been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We examined the effects and potential mechanism of glutamate-related drugs on compulsive behavior in quinpirole (QNP)-sensitized rats, to deepen our understanding of the link between OCD and glutamate.Method: This study systematically compared the effects of the partial NMDA agonist D-Cycloserine and the NMDA antagonist NVP-AAMO77, Ro25-6981 on compulsive behavior using the elevated zero maze, open field, and marble burying tests in QNP-induced OCD model.Results: The competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists NVP-AAMO77 (5 mg/kg) and Ro25-6981 (5 mg/kg) significantly inhibited anxiety-like and compulsive behavior in rats. And D-Cycloserine at all doses showed significant suppression on anxiety-like and marble-burying behavior. Glutamic acid (Glu) levels, reflecting changes in the glutamatergic neurotransmission, were significantly decreased in rat hippocampus of the NVP-AAMO77 and D-Cycloserine-treated group compared to the saline-treated group. The levels of other amino acids were unaffected. Moreover, NVP-AAMO77 significantly decreased the expression of the subunit NR2A of the NMDAR, and Ro25-6981 suppressed the level of the subunit NR2B of the NMDAR, while D-Cycloserine decreased both the subunit NR2A and NR2B of the NMDAR.Conclusion: Collectively, these findings suggest a functional role of NMDARs in anxiety and compulsive behaviors, with NMDARs inhibition promoting anxiolytic-like and anti-compulsive responses. These findings suggest that D-cycloserine, NVP-AAMO77, and Ro25-6981 could be useful drugs for the treatment of OCD, which may be due to the suppression of NR2A- or NR2B- containing NMDAR.

Chest Wall Mobility: Identification of Underlying Predictors.

OBJECTIVE: The purpose of this study was to identify factors contributing to normal mobility or hypermobility of the chest wall. METHODS: Seventy-eight young adults were divided into 2 groups: patients with normal mobility (group 1, n = 40) and hypermobility of the chest wall (group 2, n = 38). The mean mobility of the chest wall in groups 1 and 2 was 9.9 and 6.1 cm, respectively. The mean age of groups 1 and 2 was 22.2 and 21.5 years, respectively. The Brief Symptom Inventory, State-Trait Anxiety Inventory, Beck Depression Inventory, and the Perceived Stress Scale were used to evaluate the psychometric properties. Quality of life was assessed using 12-Item Short Form Health Survey. Smoking status was determined via self-report of current smoking status. Chest wall mobility was measured using thoracic and axillary cirtometry. Pulmonary functions were evaluated using a Spirobank II device. Subsequently, forced vital capacity (FVC), forced expiratory volume in 1 second, peak expiratory flow, and forced expiratory flow 25% to 75% were verified. Carefusion Micro RPM and the 6-minute walk test were used to evaluate maximal respiratory pressures and functional capacity, respectively. RESULTS: With backward linear regression models, FVC and obsessive-compulsive traits were significant predictors of chest wall mobility (R²â€¯= 0.27; P < .001 and P = .01, respectively). In logistic regression models, FVC, maximum inspiratory pressure, and obsessive-compulsive traits were significant predictors of normal mobility/hypermobility of the chest wall (R²â€¯= 0.42; P < .001, P = .01, and P = .03, respectively). CONCLUSION: Forced vital capacity, maximum inspiratory pressure, and obsessive-compulsive traits are significant predictors of chest wall mobility and normal mobility or hypermobility of the chest wall.

A study of the Repeated Actions Diary in patients suffering from obsessive compulsive disorder.

The structured Repeated Action Diary (RAD) collects in vivo data on compulsions and their various characteristics. Certain compulsions (i.e., those ending because the patient feels certain that it is safe to stop) are then compared with uncertain compulsions. The compulsion profile in patients with obsessive compulsive disorder (OCD) was assessed by using the RAD. Thirty-two patients from two sources participated in the study. Before pooling the two subgroups, we checked that they did not differ significantly with regard to demographic and clinical variables. Patients reported several categories of compulsion. The most frequently reported compulsions were washing and checking. In a given person, checking compulsions (in contrast to washing compulsions) were often produced by several different obsessions. Almost all the patients reported repeating the compulsions because of a need to feel sure. There were far more "certain" compulsions than "uncertain" compulsions. The number of repetitions was significantly lower for certain compulsions than for uncertain compulsions. The person felt greater relief from guilt and responsibility and a greater decrease in discomfort at the end of a compulsive episode for certain compulsions than for uncertain compulsions. In conclusion, the need to ritualize (prompted by uncertainty, i.e., potential danger) might explain the maintenance (or posttreatment recurrence) of OCD in many patients. The need for certainty in the completion of a compulsion may be worth considering as a therapeutic tool. The development of an approach based on the need for certainty might help to improve treatment outcomes.

Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors.

There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that, in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression, and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-containing striatal neurons of mice expressing EAAC1 leads to reduced D1R protein level and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.SIGNIFICANCE STATEMENT Genetic studies implicate Slc1a1, a gene encoding the neuronal glutamate transporter EAAC1, with obsessive-compulsive disorder (OCD). EAAC1 is abundantly expressed in the striatum, a brain region that is hyperactive in OCD. What remains unknown is how EAAC1 shapes synaptic function in the striatum. Our findings show that EAAC1 limits activation of metabotropic glutamate receptors (mGluRIs) in the striatum and, by doing so, promotes D1 dopamine receptor (D1R) expression. Targeted activation of signaling cascades coupled to mGluRIs in mice expressing EAAC1 reduces D1R expression and triggers repeated motor behaviors. These findings provide new information on the molecular basis of OCD and suggest new avenues for its treatment.

Defining Compulsive Behavior.

Compulsive tendencies are a central feature of problematic human behavior and thereby are of great interest to the scientific and clinical community. However, no consensus exists about the precise meaning of 'compulsivity,' creating confusion in the field and hampering comparison across psychiatric disorders. A vague conceptualization makes compulsivity a moving target encompassing a fluctuating variety of behaviors, which is unlikely to improve the new dimension-based psychiatric or psychopathology approach. This article aims to help progress the definition of what constitutes compulsive behavior, cross-diagnostically, by analyzing different definitions in the psychiatric literature. We searched PubMed for articles in human psychiatric research with 'compulsive behavior' or 'compulsivity' in the title that focused on the broader concept of compulsivity-returning 28 articles with nine original definitions. Within the definitions, we separated three types of descriptive elements: phenomenological, observational and explanatory. The elements most applicable, cross-diagnostically, resulted in this definition: Compulsive behavior consists of repetitive acts that are characterized by the feeling that one 'has to' perform them while one is aware that these acts are not in line with one's overall goal. Having a more unified definition for compulsive behavior will make its meaning precise and explicit, and therefore more transferable and testable across clinical and non-clinical populations.