Models Of Obsessive-compulsive Disorder Research Articles

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

Signal attenuation as a rat model of obsessive compulsive disorder.

In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

White matter lesions in patient with treatment resistant obsessive compulsive disorder: a case report

Neurobiological models of Obsessive compulsive disorder (OCD) suggest that there are structural and functional abnormalities in frontal-striatal-thalamic-cortical circuits. These cortical and subcortical microcircuits are physically and functionally connected through the white matter. Therefore, the disrupted white matter microstructure may be implicated in the pathophysiology of OCD. Neuroanatomical studies have reported various regional white matter abnormalities in patients with OCD. In this case, we present subcortical WMHs in a patient with treatment resistant OCD.

Development and validation of the Japanese version of Responsibility Attitude Scale and Responsibility Interpretations Questionnaire

Distorted beliefs about responsibility attitude and interpretation are a central theme in Salkovskis’ cognitive model of Obsessive-Compulsive Disorder (OCD). This study aimed to develop Japanese versions of the Responsibility Attitude Scale (RAS-J) and Responsibility Interpretation Questionnaire (RIQ-J). Participants in Study 1 were 118 non-clinical Japanese students who completed the RAS-J and RIQ-J to confirm the test-retest reliability of these scales. In Study 2, 98 participants (OCD group = 37; anxiety control group = 24; healthy control group = 37) completed the RAS-J, RIQ-J and other measures to assess the validity of the RAS-J and RIQ-J. As a result of analysis, The RAS-J and RIQ-J demonstrated adequate test-retest reliability and internal consistency. In addition, both scales had adequate concurrent validity, demonstrated by significant correlations with other measures of OCD, anxiety and depression. Group comparison data using ANOVA with Bonferroni method indicated that RAS-J and RIQ-J scores fo...

The experience of OCD-related intrusive thoughts in African and European Americans: Testing the generalizability of cognitive models of obsessive compulsive disorder

Cognitive theories of obsessive-compulsive disorder (OCD) emphasize the role of maladaptive appraisals and control strategies in distinguishing normal from clinically significant intrusive thoughts. Since the majority of studies testing these models utilize predominantly European American samples, the racial and ethnic generalizability of these theories is largely unknown. In the current study, African Americans (n=40) and European Americans (n=54) were interviewed about their experiences of unwanted intrusive thoughts (e.g., frequency, interference, importance, and difficulty dismissing the intrusion), as well as their appraisals and the control strategies employed to manage distress associated with their most distressing intrusive thought. Participants also completed a self-report measure of OC symptoms. Results indicated that African American and European American participants reported similar experiences of OCD-related intrusions, appraisals, and control strategies; however, the groups showed different patterns of relations between intrusion appraisals, control strategies, and self-reported OC symptoms. These findings suggest that race-associated factors may play a role in the comparative experience of OCD-related phenomena between African American and European American individuals. Theoretical and clinical implications are discussed within cognitive models of OCD.

Part 2. They scare because we care: The relationship between obsessive intrusive thoughts and appraisals and control strategies across 15 cities

Cognitive models of Obsessive Compulsive Disorder (OCD) purport that obsessions are normal intrusive thoughts that are misappraised as significant, leading to negative emotional responses and maladaptive attempts to control the thoughts and related emotions. This paper utilised a large multi-national dataset of interview data regarding intrusive thoughts, to investigate three questions related to the cognitive model of OCD and to its stability across cultures. First, the paper aimed to investigate the implicit yet-hitherto-untested assumption of cognitive models that misappraisals and control strategies for intrusive thoughts relate similarly across cultures. Second, this study aimed to build upon recent studies categorising intrusive thoughts into repugnant and non-repugnant categories, by investigating whether the content of intrusive thought moderates the relationship between the thoughts and appraisals and control strategies. Finally, this study aimed to provide further evidence regarding whether general beliefs implicated in cognitive models of OCD (e.g., responsibility, importance of thoughts) influence the occurrence of intrusions via maladaptive appraisals and control strategies. Overall, it was found that while overall intrusive thought frequency, distress, ease and importance of dismissal all varied significantly by site, their relationship with appraisals and control strategies did not. Generally, appraisals and action taken to confront the thought were the more consistent predictors, with the notably caveat that the relationship between thought frequency and appraisals was not strong. Second, repugnant vs. non-repugnant thought-content differed only with respect to thought frequency, but thought-content did not moderate the relationship between intrusive thoughts and control strategies and appraisals. Finally, appraisals and control strategies generally partially mediated the relationship between general OCD-related beliefs and the occurrence of, and distress associated with, intrusive thoughts. The results are taken to add credence to cognitive models of OCD and their validity across cultures.

Literature Review of the Metacognitive Model of Obsessive Compulsive Disorder

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A Metacognition Approach to Characteristics of Obsessive-Compulsive Disorder, Model and Intervention

The metacognitive model of obsessive-compulsive disorder(OCD) emphasizes that metacognitive beliefs are a key factor in OCD pathology. OCD patients have a series of metacognitive problems, such as incorrect metacognitive knowledge beliefs, negative metacognitive experiences and inappropriate use of metacognitive strategies. Metacognitive therapy for OCD has a good treatment efficacy in the individual intervention and group intervention study, with a focus on the importance of thinking processes(such as self-focused attention, perseverative thinking styles of worry, attention strategies of threat monitoring and so on) rather than the content of thoughts. Future research should examine the memory and other metacognitive characteristics for OCD from the perspectives of cognitive neuroscience and replicate and extend metacognitive model of OCD.

Spotlight on a mouse model of obsessive-compulsive disorder

It has been shown these last years that optogenetic tool, that uses a combination of optics and genetics technics to control neuronal activity with light on behaving animals, allows to establish causal relationship between brain activity and normal or pathological behaviors [3]. In combination with animal model of neuropsychiatric disorder, optogenetic could help to identify deficient circuitry in numerous pathologies by exploring functional connectivity, with a specificity never reached before, while observing behavioral and/or physiological correlates. To illustrate the promising potential of these tools for the understanding of psychiatric diseases, we will present our recent study where we used optogenetic to block abnormal repetitive behavior in a mutant mouse model of obsessive-compulsive disorder [1]. Using a delay-conditioning task we showed that these mutant mouse model had a deficit in response inhibition that lead to repetitive behaviour. With optogenetic, we could stimulate a specific circuitry in the brain that connect the orbitofrontal cortex with the basal ganglia; a circuitry that has been shown to be dysfunctional in compulsive behaviors. We observed that these optogenetic stimulations, through their effect on inhibitory neurons of the basal ganglia, could restore the behavioral response inhibition and alleviate the compulsive behavior. These findings raise promising potential for the design of targeted deep brain stimulation therapy for disorders involving excessive repetitive behavior and/or for the optimization of already existing stimulation protocol [2].

Validation of a Chinese Version of the Obsessive Beliefs Questionnaire

Cognitive models of obsessive-compulsive disorder (OCD) assign a central role to maladaptive beliefs. Evaluation of these OCD beliefs in Western countries is commonly accomplished using the Obsessive Beliefs Questionnaire (OBQ) and is important for conceptualizing and treating OCD. It remains unclear if Western models of OCD beliefs are appropriate for sufferers in some non-Western regions, such as China, which represents nearly 20 % of the world population. Thus, the aim of present study is to examine the psychometric properties of a Chinese translation of the OBQ in three samples: 1,322 undergraduates, 139 patients with OCD, and 79 patients with other anxiety disorders. Confirmatory factor analysis revealed poor fit for multiple English-based models of the OBQ. However, an exploratory factor analysis supported an OBQ model that differs slightly from the English version: (1) Perfectionism/Certainty (P/C), (2) Over-Estimation of Threat (T), (3) Importance of Thoughts/Responsibility for Harm (I/R). This Chinese version of the OBQ (C-OBQ) contains 30 items and shows adequate internal consistency, test-retest reliability, construct validity, and criterion-related validity. In China, the C-OBQ may be a useful instrument for delineating cognitive patterns associated with OCD to inform research and treatment.

Optogenetic models for obsessive compulsive disorder (OCD) in mice

Optogenetic models for obsessive compulsive disorder (OCD) in mice

Oxcarbazepine and fluoxetine protect against mouse models of obsessive compulsive disorder through modulation of cortical serotonin and creb pathway

The serotonergic system is suggested to be dysregulated in obsessive compulsive disorder (OCD) as selective serotonin reuptake inhibitors have emerged as the mainstay in the treatment of this disorder. Oxcarbazepine (OXC), a second generation antiepileptic drug, enhances hippocampal serotonin (5-HT) levels. The aim of the present study was to screen the anti-OCD effects of OXC on marble burying behaviour (MBB) and 8-OHDPAT-induced disruption of alternation, two most studied paradigms of OCD, in rodents. Here we show that 8-OHDPAT (2.8mg/kg) significantly increases spontaneous alternation behaviour (SAB) score in a T-maze. Fluoxetine (FLX), an SSRI on chronic administration (10mg/kg, 21 days) restored the increase in SAB induced by 8-OHDPAT in mice which is in line with the findings earlier reported for rats. Hence, we present the first mouse model of OCD induced by 2.8mg/kg of 8-OHDPAT. Chronic administration (21 days) of OXC (20 and 40mg/kg) also restored the SAB disrupted by 8-OHDPAT which was comparable to FLX. Likewise in MBB test, FLX and OXC significantly reduced the number of marbles buried. 8-OHDPAT induced OCD was associated with a concomitant decrease in basal 5-HT levels (88%) and depletion of basal CREB (32%) in the frontal cortex. Chronic treatment with FLX and OXC effectively mitigated the lowering effects of 8-OHDPAT on cortical 5-HT, and enabled an efficient recovery in basal CREB levels. Our results on FLX and OXC provide the indication that their anti-OCD effects in part, might be elicited through modulation of 5HT levels and CREB pathway.

Toward a Neuroanatomy of Obsessive-Compulsive Disorder Revisited

Since the publication of Insel’s commentary Towards a Neuroanatomy of Obsessive-Compulsive Disorder ( 1 Insel T.R. Towards a neuroanatomy of obsessive compulsive disorder. Arch Gen Psychiatry. 1992; 49: 739-744 Crossref PubMed Scopus (412) Google Scholar ) 20 years ago, the finding of increased regional metabolic activity in orbitofrontal cortex and caudate in obsessive-compulsive disorder (OCD) patients versus controls, in both resting and symptomatic states, has been one of the most replicable findings in psychiatric imaging. Using resting positron emission tomography, Schwartz et al. ( 2 Schwartz J.M. Stoessel P.W. Baxter L.R. Martin K.M. Phelps M.E. Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive compulsive disorder. Arch Gen Psychiatry. 1996; 53: 109-113 Crossref PubMed Scopus (546) Google Scholar ) were the first to report on a functional connectivity measure that led to the speculation that the orbital striatal thalamic loop was overly synchronized in OCD and that successful behavioral or pharmacologic treatment led to the desynchronization of the network. Since that initial study, advances in Bayesian dynamic causal modeling have allowed us to gain an understanding of how slow resting state rhythms are synchronized across brain regions and has led to a new era in exploring functional connectivity in psychiatric disease ( 3 Fox M.D. Raichle M.E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Neurosci Rev. 2007; 8: 700-711 Crossref PubMed Scopus (4769) Google Scholar ). Functional connectivity studies have brought home the importance of complex network connections as well as the significance of synchrony versus desynchrony between structures as a potential target for therapeutic intervention. In 2009 Harrison et al. ( 4 Harrison B.J. Soriano-Mas C. Pujol J. Ortiz H. Lopez-Sola M. Hernandez-Ribas R. et al. Altered corticostriatal functional connectivity in obsessive compulsive disorder. Arch Gen Psychiatry. 2009; 66: 1189-1200 Crossref PubMed Scopus (419) Google Scholar ) were the first of several groups to report on resting-state functional connectivity in OCD. Their major findings confirmed previous positron emission tomography and functional magnetic resonance imaging data that pointed to abnormalities in orbital striatal function in OCD and whose magnitude was correlated with OCD severity. In the current issue, Harrison et al. ( 4 Harrison B.J. Soriano-Mas C. Pujol J. Ortiz H. Lopez-Sola M. Hernandez-Ribas R. et al. Altered corticostriatal functional connectivity in obsessive compulsive disorder. Arch Gen Psychiatry. 2009; 66: 1189-1200 Crossref PubMed Scopus (419) Google Scholar ) have replicated their initial findings with a much larger sample of 74 patients and controls and report on the similarities and differences in functional connectivity ( 5 Harrison BJ, Pujol J, Cardoner N, Deus J, Alonso P, López-Solà M, et al. (2013): Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder. Biol Psychiatry 73:321–328. Google Scholar ) that are correlated with OCD symptom dimensions measured by the Dimensional Yale Brown Obsessive Compulsive Scale (DYBOCS) ( 6 Mataix-Cols D. Rosario-Campos M.S. Leckman J.F. A multidimensional model of obsessive compulsive disorder. Am J Psychiatry. 2005; 162: 228-238 Crossref PubMed Scopus (728) Google Scholar ). The findings validate a host of other clinical, imaging, and genetic findings that demonstrate both the overlap and unique features of symptom dimensions in OCD. These data support OCD’s phenotypic and etiologic heterogeneity. Brain Corticostriatal Systems and the Major Clinical Symptom Dimensions of Obsessive-Compulsive DisorderBiological PsychiatryVol. 73Issue 4PreviewFunctional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder’s prominent clinical heterogeneity. Full-Text PDF

Ritualistic Chewing Behavior induced by mCPP in the rat is an animal model of Obsessive Compulsive Disorder

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6–8week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3mg/kg), the dopamine antagonist haloperidol (1mg/kg), the GABA modulator diazepam (10mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14days of chronic treatment were required for blockade of the mCPP-evoked response.The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD.

“Not just right experiences” predict obsessive–compulsive symptoms in non-clinical Italian individuals: A one-year longitudinal study

The cognitive model of obsessive compulsive disorder (OCD) proposes that certain beliefs may contribute to the development and maintenance of this disorder. However, the role of such beliefs in OCD symptomatology is not clear, despite many investigations conducted so far. In the effort to identify other constructs and processes related to OCD, the phenomenon labeled “not just right experiences” (NJREs) has been receiving increasing attention. NJREs can be defined as “the subjective sense that something isn't just as it should be”, an unsettled feeling because something in the individuals or in the world around them is not right. In the current research, measures of NJREs, OC symptoms, general distress (i.e., anxiety, depression), and looming maladaptive style were administered to 187 college students on three occasions six months apart (baseline, six-months, and one-year later). Linear mixed effects regression models indicated that NJREs explained OC symptoms variation over time even when general distress and looming style were accounted for. Investigation of distinct OC symptoms indicated that NJREs were associated also with washing, ordering and obsessing symptoms, but not with checking ones. These findings suggest that the concept of NJREs may contribute to improve current psychological and biological model of OCD.

The extended fronto-striatal model of obsessive compulsive disorder: convergence from event-related potentials, neuropsychology and neuroimaging

In this work, we explored convergent evidence supporting the fronto-striatal model of obsessive-compulsive disorder (FSMOCD) and the contribution of event-related potential (ERP) studies to this model. First, we considered minor modifications to the FSMOCD model based on neuroimaging and neuropsychological data. We noted the brain areas most affected in this disorder -anterior cingulate cortex (ACC), basal ganglia (BG), and orbito-frontal cortex (OFC) and their related cognitive functions, such as monitoring and inhibition. Then, we assessed the ERPs that are directly related to the FSMOCD, including the error-related negativity (ERN), N200, and P600. Several OCD studies present enhanced ERN and N2 responses during conflict tasks as well as an enhanced P600 during working memory (WM) tasks. Evidence from ERP studies (especially regarding ERN and N200 amplitude enhancement), neuroimaging and neuropsychological findings suggests abnormal activity in the OFC, ACC, and BG in OCD patients. Moreover, additional findings from these analyses suggest dorsolateral prefrontal and parietal cortex involvement, which might be related to executive function (EF) deficits. Thus, these convergent results suggest the existence of a self-monitoring imbalance involving inhibitory deficits and executive dysfunctions. OCD patients present an impaired ability to monitor, control, and inhibit intrusive thoughts, urges, feelings, and behaviors. In the current model, this imbalance is triggered by an excitatory role of the BG (associated with cognitive or motor actions without volitional control) and inhibitory activity of the OFC as well as excessive monitoring of the ACC to block excitatory impulses. This imbalance would interact with the reduced activation of the parietal-DLPC network, leading to executive dysfunction. ERP research may provide further insight regarding the temporal dynamics of action monitoring and executive functioning in OCD.

Effects of Obsessive-Compulsive Symptoms on Neuropsychological Test Performance: Complicating an Already Complicated Story

Theoretical models of obsessive-compulsive disorder (OCD) implicate neurocognitive dysfunction, particularly deficits in nonverbal memory and executive functioning, in the pathogenesis of the disorder. The opposite hypothesis (poor performance in neuropsychological test as an epiphenomenon of OCD symptoms) has rarely been contemplated although checking behavior, obsessional doubt, lack of motivation, and slowness as well as preoccupation with touching objects may result in secondary test impairment and mimic manifestations of neural dysfunction. A total of 60 patients with OCD and 30 healthy controls were tested with a multi-functional neuropsychological battery. At the end of the testing participants were asked about their effort and the severity of OCD symptoms during task execution. Up to one fourth of the OCD patients affirmed OCD-related worries and motivational problems during task execution. Poor motivation and checking were significantly associated with enhanced objective performance deficits. Whereas the present study does not negate a role of neurocognitive deficits in the formation of OCD, in our view the reverse relationship should be contemplated as well. We advise researchers to pay closer attention to possible confounds that may mediate the relationship between OCD and neurocognition. Limitations of the study are discussed.

Poor inhibitory control and neurochemical differences in high compulsive drinker rats selected by schedule-induced polydipsia

Schedule-induced polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, has been proposed as a model for obsessive-compulsive disorder, schizophrenia and drug abuse. The purpose of this study is to investigate if individual differences in SIP reflect psychopathological behavioural traits related to lack of inhibitory control and reactivity to novelty, and if these differences have neurochemical correlates. Outbred Wistar rats were selected for being either high (HD) or low (LD) drinkers according to their SIP behaviour. We tested locomotor reactivity to a novel environment and inhibitory control on the five-choice serial reaction time task (5-CSRTT), under baseline vs. extinction conditions and following challenge with D: -amphetamine (saline, 0.5 or 1 mg/kg). Post-mortem analyses of the monoaminergic levels in different brain regions were also analysed. Compared to LD animals, HD rats exhibiting SIP acquisition showed no differences in spontaneous locomotor reactivity to novelty. On the 5-CSRTT, HD rats showed a greater increase in perseverative responses under extinction, a trend towards elevated premature responses on baseline, and a significantly greater elevation of premature responses to D: -amphetamine 0.5 mg/kg. The HD animals also exhibited increased serotonin activity in the amygdala, and correlational analyses between the rate of drinking on SIP and monoamine levels also revealed altered dopaminergic mesolimbic function. These findings show that HD rats selected by SIP exhibit compulsive and impulsive behaviour based on measures of performance on the five-choice serial reaction time task and associated with changes in monoaminergic systems in limbic-striatal circuitry.

S.06.05 Gender and distinct correlates of disgust sensitivity in OCD

Cognitive models of Obsessive Compulsive Disorder (OCD) purport that obsessions are normal intrusive thoughts that are misappraised as significant, leading to negative emotional responses and maladaptive attempts to control the thoughts and related emotions. This paper utilised a large multi-national dataset of interview data regarding intrusive thoughts, to investigate three questions related to the cognitive model of OCD and to its stability across cultures. First, the paper aimed to investigate the implicit yet-hitherto-untested assumption of cognitive models that misappraisals and control strategies for intrusive thoughts relate similarly across cultures. Second, this study aimed to build upon recent studies categorising intrusive thoughts into repugnant and non-repugnant categories, by investigating whether the content of intrusive thought moderates the relationship between the thoughts and appraisals and control strategies. Finally, this study aimed to provide further evidence regarding whether general beliefs implicated in cognitive models of OCD (e.g., responsibility, importance of thoughts) influence the occurrence of intrusions via maladaptive appraisals and control strategies. Overall, it was found that while overall intrusive thought frequency, distress, ease and importance of dismissal all varied significantly by site, their relationship with appraisals and control strategies did not. Generally, appraisals and action taken to confront the thought were the more consistent predictors, with the notably caveat that the relationship between thought frequency and appraisals was not strong. Second, repugnant vs. non-repugnant thought-content differed only with respect to thought frequency, but thought-content did not moderate the relationship between intrusive thoughts and control strategies and appraisals. Finally, appraisals and control strategies generally partially mediated the relationship between general OCD-related beliefs and the occurrence of, and distress associated with, intrusive thoughts. The results are taken to add credence to cognitive models of OCD and their validity across cultures.

Animal models of obsessive compulsive disorder: recent findings and future directions

Introduction: Obsessive compulsive disorder (OCD) is a debilitating condition with limited treatment options. OCD is heterogeneous with respect to the content of obsessions and compulsions and their underlying motivation, among other characteristics. Animal models have provided important insights into the pathophysiology of OCD.Areas covered: The phenomenology of OCD is discussed, with emphasis on clinically-relevant subgroups. The paper also discusses the advantages and limitations of animals as models of OCD, along with considerations on assessing their validity. A PubMed database search using the terms ‘animal model’ and ‘obsessive compulsive disorder’ revealed ongoing studies in several models, including stereotypy in the deer mouse, quinpirole-induced checking, spontaneous alternation, compulsive lever pressing, genetic models, pathogenic models and models involving normal compulsive-like behavioral patterns. These models are presented with respect to their similarity to specific features of OCD and the information gained from them. Studies in many of these models point to the participation of corticostriatal thalamocortical circuitry and corticostriatal glutamate neurotransmission in the pathophysiology of compulsive-like behavior.Expert opinion: The use of animal models takes us beyond simple serotonin- or dopamine-based models of OCD that are founded on the often limited, and still unexplained, response of OCD symptoms to serotonin reuptake inhibitors or antipsychotic therapy. Pharmacological challenges that selectively target neurochemical systems that modulate either corticostriatal glutamate or striatal dopamine neurotransmission, or indeed both, should be investigated in animal models of compulsive-like behavior. Such systems include metabotropic glutamate, adenosine and endocannabinoid receptors, among others.