From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD)

Eilam, David

doi:10.1016/j.neubiorev.2016.12.034

Cited by 13 publications

(21 citation statements)

References 49 publications

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“…To identify the neural circuitry controlling OCD checking behaviors, it is necessary to consider behavior in animals that resembles the checking symptoms of OCD patients. Given that rats treated with the dopamine agonist quinpirole develop checking behavior, we developed a convenient mouse model of OCD-like checking behavior in favor of optogenetic manipulation (22)(23)(24). To explore mouse behavior after chronic quinpirole treatment, we designed an experimental setup in which mice received 10% sucrose solution and water ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Sun

Song

Tian

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world’s population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA–mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.

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Section: Resultsmentioning

confidence: 99%

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Sun

Song

Tian

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…To improve the comparison of human and animal results, similar experimental procedures across species are indispensable in order to ensure comparable task parameters and psychometric properties 24,25 , and, hence, comparable results 26 . In case of reversal learning tasks, it has been demonstrated that the neurobiological processes may differ according to sensory modalities, impeding translational value in approaches using different stimulus modality across species 27 .…”

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confidence: 99%

A cross-species assessment of behavioral flexibility in compulsive disorders

et al. 2021

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Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. However, experimental evidence has proven inconsistent across human and animal models of compulsive-like behavior. In the present study, applying a similarly-designed reversal learning task in two different species, which share a common symptom of compulsivity (human OCD patients and Sapap3 KO mice), we found no consistent link between compulsive behaviors and lack of behavioral flexibility. However, we showed that a distinct subgroup of compulsive individuals of both species exhibit a behavioral flexibility deficit in reversal learning. This deficit was not due to perseverative, rigid behaviors as commonly hypothesized, but rather due to an increase in response lability. These cross-species results highlight the necessity to consider the heterogeneity of cognitive deficits in compulsive disorders and call for reconsidering the role of behavioral flexibility in the aetiology of compulsive behaviors.

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“…Inclusion criteria for the clinical sample were: (1) Hebrew language spoken as mother tongue; (2) self-completion of the questionnaires; (3) self-referral; (4) at least 10 years of formal education; (5) 391 schizophrenia or psychosis; (2) any current legal problems; (3) dyslexia; (4) motor or neurological disorder (tic disorder or Tourette syndrome were not excluded); (5) current or past diagnosis of post-traumatic stress disorder; (6) diagnosis of obsessive-compulsive personality disorder (OCPD), since we presumed that this disorder may also affect the filling-out of questionnaires.…”

Section: Study Samplementioning

confidence: 99%

“…Novel research approaches OCD behavior from a different perspective, namely, human ethology, which examines behavior on the basis of observations made by the clinician rather than on the basis of evidence provided by the subject's own introspective complaints [1] . This approach is based on recently implemented tools derived from previous studies in an animal model of OCD [2][3][4][5] to study motor rituals in OCD patients while scrutinizing the spatiotemporal structure of OCD rituals. For analysis, rituals go through segmentation into a sequence of visits to objects or locations, a segmentation that is based on studying rituals in an animal model of OCD.…”

Section: Introductionmentioning

confidence: 99%

Nonfunctional Redundant Acts Characterize OCD, Even in OCD-Unrelated Tasks: A Demonstration in Questionnaire Completion

Amitai

Arnon²,

Shaham³

et al. 2017

Psychopathology

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Background: Ethological methods used to analyze human obsessive-compulsive disorder (OCD) rituals demonstrated excess of unnecessary repetitions as well as irrelevant, idiosyncratic acts (additions) compared to normal activity. A question that still remains is whether these well-known repetitions and additions are manifested in behaviors unrelated to the OCD rituals. Our objectives were to: (1) assess whether OCD-related repetitions and additions as found in previous studies also affect the patients' activity of filling out questionnaires and (2) evaluate the specificity of these behaviors to OCD as opposed to other anxiety disorders and healthy controls. Sampling and Methods: Several standardized disorder-specific self-report questionnaires were used in order to assess the patient's psychopathologies. The style of filling-out these questionnaires by OCD and non-OCD anxiety outpatients and normal controls was analyzed. Four categories were used: omissions, repetitions, corrections, and additions. Results: The OCD group scored significantly higher on the number of additions as compared with both the anxiety group and the nonclinical group, and significantly higher on the number of corrections and repetitions as compared with the nonclinical group. Conclusions: The hallmarks of OCD, repetitions and additions, are manifested not only in the patient's rituals and thoughts, but in apparently “neutral” tasks that do not a priori involve the intrusive thoughts, urges, and images typical of obsessive-compulsive behavior. Additions seem to be more specific to OCD than repetitions. These two executive faults impede routine functionality of OCD patients in tasks related and unrelated to their rituals. Our study delineates simple, observable behavioral characteristics that distinguish between OCD and non-OCD anxiety patients as well as healthy individuals. These symptomatic behaviors may offer a clue to personality traits or deficits in executive functions that possibly play a part in the pathophysiology of OCD. Our results are an additional indication that nonfunctionality in obsessive-compulsive behavior deserves full attention for a better understanding of the psychopathological mechanisms of OCD.

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From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD)

Cited by 13 publications

References 49 publications

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

A cross-species assessment of behavioral flexibility in compulsive disorders

Nonfunctional Redundant Acts Characterize OCD, Even in OCD-Unrelated Tasks: A Demonstration in Questionnaire Completion

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