Translational approaches to obsessive-compulsive disorder: From animal models to clinical treatment

Na Fineberg, Sr Chamberlain, Eric Hollander, V. Boulougouris, Tw Robbins

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.

Original languageEnglish (US)
Pages (from-to)1044-1061
Number of pages18
JournalBritish Journal of Pharmacology
Volume164
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Obsessive-Compulsive Disorder
Animal Models
Compulsive Behavior
Obsessive Behavior
Corpus Striatum
Genetic Models
Therapeutic Uses
Reproducibility of Results
Cognition
Pharmacology
Psychology
Brain
Research
Pharmaceutical Preparations

Keywords

  • compulsivity
  • dopamine
  • flexibility
  • impulsivity
  • inhibition
  • OCD
  • serotonin
  • translational

ASJC Scopus subject areas

  • Pharmacology

Cite this

Translational approaches to obsessive-compulsive disorder : From animal models to clinical treatment. / Fineberg, Na; Chamberlain, Sr; Hollander, Eric; Boulougouris, V.; Robbins, Tw.

In: British Journal of Pharmacology, Vol. 164, No. 4, 10.2011, p. 1044-1061.

Research output: Contribution to journalArticle

Fineberg, Na ; Chamberlain, Sr ; Hollander, Eric ; Boulougouris, V. ; Robbins, Tw. / Translational approaches to obsessive-compulsive disorder : From animal models to clinical treatment. In: British Journal of Pharmacology. 2011 ; Vol. 164, No. 4. pp. 1044-1061.
@article{32d5cf1d385746e48690e5c7816699eb,
title = "Translational approaches to obsessive-compulsive disorder: From animal models to clinical treatment",
abstract = "Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.",
keywords = "compulsivity, dopamine, flexibility, impulsivity, inhibition, OCD, serotonin, translational",
author = "Na Fineberg and Sr Chamberlain and Eric Hollander and V. Boulougouris and Tw Robbins",
year = "2011",
month = "10",
doi = "10.1111/j.1476-5381.2011.01422.x",
language = "English (US)",
volume = "164",
pages = "1044--1061",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Translational approaches to obsessive-compulsive disorder

T2 - From animal models to clinical treatment

AU - Fineberg, Na

AU - Chamberlain, Sr

AU - Hollander, Eric

AU - Boulougouris, V.

AU - Robbins, Tw

PY - 2011/10

Y1 - 2011/10

N2 - Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.

AB - Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.

KW - compulsivity

KW - dopamine

KW - flexibility

KW - impulsivity

KW - inhibition

KW - OCD

KW - serotonin

KW - translational

UR - http://www.scopus.com/inward/record.url?scp=80053331478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053331478&partnerID=8YFLogxK

U2 - 10.1111/j.1476-5381.2011.01422.x

DO - 10.1111/j.1476-5381.2011.01422.x

M3 - Article

C2 - 21486280

AN - SCOPUS:80053331478

VL - 164

SP - 1044

EP - 1061

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 4

ER -