The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers

Chamberlain, Samuel R.; Blackwell, Andrew D.; Fineberg, Naomi; Robbins, Trevor W.; Sahakian, Barbara J.

doi:10.1016/j.neubiorev.2004.11.006

Cited by 725 publications

(614 citation statements)

References 190 publications

(197 reference statements)

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“…Despite the substantial recent interest in cognitive impairments as endophenotypes of diverse psychiatric disorders (including schizophrenia 57,58 bipolar disorder, 59 attention-deficit/hyperactivity disorder 60,61 and obsessive-compulsive disorder 62 ) replicated associations between candidate genes and specific cognitive functions remain elusive. The marginal nature of the association between COMT genotype and WCST performance revealed here may lessen the popularity of the WCST as a candidate endophenotype for schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

et al. 2007

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The catechol-O-methyltransferase (COMT) Val 158 Met polymorphism is hypothesized to affect executive function in patient and control populations. Studies inconsistently report better performance on the Wisconsin Card Sort Test (WCST) in individuals with one or more Met alleles. We conducted a meta-analysis of studies published until August 2006 that reported WCST perseverative errors from healthy volunteers or patients with schizophrenia-spectrum disorders. Twelve studies met inclusion criteria (total n = 1910) providing 10 samples each of patients and controls. In healthy controls, individuals with the Met/Met genotype performed better than those with the Val/Val genotype (d = 0.29; 95% confidence interval (CI) 0.02-0.55; P = 0.03), but this was not supported in the patient sample (d = À0.07; 95% CI À0.40 to 0.26; P = 0.68). Post hoc analyses suggested that Val and Met alleles are codominant in their effects on cognition. Effect size was greater in studies published at an earlier date and may also be larger in non-Caucasian samples. Gender did not affect the results. There was no evidence of publication bias. We conclude that there is small but significant relationship between Val 158 Met genotype and executive function in healthy individuals but not in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

et al. 2007

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“…Thus, problems suppressing or inhibiting inappropriate behavior could underpin both impulsive and compulsive symptomatology (Chamberlain et al, 2005;Stein et al, 2006). ADHD is a disorder of early onset characterized by poorly conceived, impulsive actions and robust impairment in motor inhibition as measured on tasks such as the SSRT (Aron et al, 2003;Lijffijt et al, 2005).…”

Section: Dissociating Impulsive and Compulsive Disorders Using Neuropmentioning

confidence: 99%

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

Fineberg

Potenza

Chamberlain

et al. 2009

Neuropsychopharmacol

592

468

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Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive-compulsive disorder (OCD), obsessive-compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field.

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“…Pathological levels of inhibition failure and impulsivity are common to psychiatric conditions such as attention deficit and hyperactivity disorder (ADHD) (Aron and Poldrack, 2005;Oosterlaan et al, 1998;Rubia et al, 2007;Schachar et al, 1995), Parkinson's disease (Gauggel et al, 2004;van den Wildenberg et al, 2006), schizophrenia (Bellgrove et al, 2006), obsessive-compulsive disorder (Chamberlain et al, 2005;Penades et al, 2007), and chronic drug abuse (eg cocaine (Fillmore and Rush, 2002), amphetamine , and methamphetamine (Monterosso et al, 2005)). …”

Section: Introductionmentioning

confidence: 99%

Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition

Eagle

Lehmann

Theobald

et al. 2008

Neuropsychopharmacol

123

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Central serotonin (5-HT) function is thought to be a critical component of behavioral inhibition and impulse control. However, in recent clinical studies, 5-HT manipulations failed to affect stop-signal reaction time (SSRT), which is a fundamental process in behavioral inhibition. We investigated the effect of central 5-HT depletion (intracerebroventricular 5,7-dihydroxytryptamine) in rats on two aspects of behavioral inhibition, SSRT and 'waiting', using the stop-signal task. 5-HT depletion had no effects on SSRT or any other primary measure on the stop-signal task. However, within the same task, there was a deficit in 'waiting' in 5-HT-depleted rats when they were required to withhold from responding in the terminal element of the stop-signal task for an extended period. D-Amphetamine had dosedependent, but not 5-HT-dependent effects on SSRT. Conversely, the dose that tended to improve, or decrease, SSRT (0.3 mg/kg) impaired the ability to wait, again independently of 5-HT manipulation. These findings suggest that SSRT and 'waiting' are distinct measures of behavioral inhibition, and show that 5-HT is critical for some forms of behavioral inhibition but not others. This has significant implications for the treatment of conditions such as attention deficit and hyperactivity disorder, substance abuse, and affective disorders, in which inhibitory and impulse-control deficits are common.

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The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers

Cited by 725 publications

References 190 publications

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

Effects of the catechol-O-methyltransferase Val158Met polymorphism on executive function: a meta-analysis of the Wisconsin Card Sort Test in schizophrenia and healthy controls

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

Serotonin Depletion Impairs Waiting but not Stop-Signal Reaction Time in Rats: Implications for Theories of the Role of 5-HT in Behavioral Inhibition

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