Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder
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OBJECTIVE: Obsessive-compulsive disorder (OCD) is highly heritable. Attempts to delineate precise genetic contributions have met with limited success. There is an ongoing search for intermediate cognitive brain markers (endophenotypes) that may help clarify genetic contributions. The aim was to assess inhibitory control processes in unaffected first-degree relatives of OCD patients for the first time with objective tests. METHOD: The Intradimensional/Extradimensional Shift, Stop-Signal, and Cambridge Gamble tasks were administered to 20 unaffected first-degree relatives, 20 OCD patient probands with washing/checking symptoms, and 20 healthy matched comparison subjects without a family history of OCD. RESULTS: Unaffected first-degree relatives and OCD patient probands showed cognitive inflexibility (extradimensional set shifting) and motor impulsivity (stop-signal reaction times). Decision making (Cambridge Gamble task) was intact. CONCLUSIONS: Deficits in cognitive flexibility and motor inhibition may represent cognitive endophenotypes for OCD. Such measures will play a key role in understanding genotype/phenotype associations for OCD and related spectrum conditions.
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Cognitive inflexibility deficits persist in remitted patients and are also observed in unaffected first-degree relatives.
“Importantly, these deficits persist in remitted patients and are also observed in unaffected first-degree relatives (10, 11, 19), supporting the view that cognitive inflexibility represents a candidate endophenotype (or trait-like marker) of OCD.”
From Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review (2026) · cites this paper as [19]
The Abstract Results and Discussion report cognitive inflexibility in unaffected first-degree relatives of OCD patients, supporting that part of the claim and the proposed endophenotype interpretation. The paper does not examine whether deficits persist in remitted patients. (LLM, conf=0.87)
Experimental — accuracy not yet measuredImpaired action cancelation and action restraint has been described for OCD; patients showed increased SSRT in the Stop-signal task and higher error rates on the Go/No Go task compared with healthy control subjects.
“Impaired action cancelation and action restraint has been described for OCD (Chamberlain et al., 2007b; Penades et al., 2007); patients showed increased SSRT (i.e., slower inhibition) in the Stop-signal task and higher error rates on the Go/No Go task compared with healthy control subjects.”
From Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders (2014) · cites this paper as Chamberlain et al., 2007b
The Results report that OCD patients had significantly longer stop-signal reaction times than healthy comparison subjects, supporting the action-cancelation finding. The Method lists the tasks administered, but not a Go/No Go task; our copy does not support the claim about higher Go/No Go error rates or action restraint. (LLM, conf=0.88)
Experimental — accuracy not yet measuredExperimental studies using stop-signal, ID/ED set-shifting, reversal-learning, and Tower of London planning tasks have shown that patients with OCD often require greater cognitive effort to inhibit prepotent responses, adapt to changing contingencies, or organise goal-directed behaviour.
“Experimental studies using tasks such as the stop-signal task, intradimensional/extradimensional (ID/ED) set-shifting task, reversal-learning paradigms, and Tower of London planning tasks have further shown that patients with OCD often require greater cognitive effort to inhibit prepotent responses, adapt to changing contingencies, or organise goal-directed behaviour [5,6,7,8].”
From Electrophysiological Correlates of Cognitive Dysfunction in Obsessive-Compulsive Disorder (OCD): A Systematic and Mechanistic Review of EEG, ERP, and QEEG Evidence (2026) · cites this paper as [8]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDeficits in motor response inhibition were also observed in unaffected first-degree relatives of OCD patients.
“Deficits in motor response inhibition were also observed in unaffected first-degree relatives of OCD patients (Chamberlain et al., 2007b; Menzies et al., 2007), suggesting that motor response inhibition may be considered an endophenotype”
From Response Inhibition and Interference Control in Obsessive–Compulsive Spectrum Disorders (2014) · cites this paper as Chamberlain et al., 2007b
OCD patients have dysfunction in core neural processes mapped onto CSTC circuits, such as response inhibition and sensorimotor gating.
“evidence from recent human studies suggests that OCD patients have dysfunction in core neural processes mapped onto CSTC circuits, such as response inhibition 70,71,72 and sensorimotor gating 73.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [72]
OCD is associated with deficits in switching between rules (extradimensional set-shifting).
“and switching between rules (extradimensional set-shifting) (22)”
From Enhanced avoidance habits in obsessive-compulsive disorder (2014) · cites this paper as [22]
Behaviorally, OCD patient probands and their unaffected first-degree relatives showed cognitive inflexibility.
“Behaviorally, OCD patient probands and their unaffected first-degree relatives (UFDR) showed cognitive inflexibility (Chamberlain et al., 2007).”
From Imbalance between the caudate and putamen connectivity in obsessive–compulsive disorder (2022) · cites this paper as Chamberlain et al., 2007
The increased caudate connectivity deficits in OCD represent trait rather than state impairments, and can exist in the absence of medication confounds and clinical phenotype.
“These deficits represent trait rather than state impairments, that can exist in the absence of medication confounds and clinical phenotype (Chamberlain et al., 2007).”
From Imbalance between the caudate and putamen connectivity in obsessive–compulsive disorder (2022) · cites this paper as Chamberlain et al., 2007
Impaired motor response inhibition is observed in unaffected first-degree relatives of OCD patients, suggesting that motor response inhibition may be an endophenotype for OCD.
“Impaired motor response inhibition is also observed in unaffected first-degree relatives of OCD patients (Chamberlain et al., 2007) suggesting that motor response inhibition may be considered an endophenotype for OCD.”
From The role of habit in compulsivity (2016) · cites this paper as Chamberlain et al., 2007
Differences in SSRT have been found for adolescents and adults with OCD.
“In contrast, differences in SSRT have been found for adolescents and adults with OCD (Chamberlain et al., 2007; Kang et al., 2013; Penadés et al., 2007; de Wit et al., 2012), suggesting that for individuals with OCD, problems with cognitive control may emerge later in development.”
From No evidence of differences in cognitive control in children with autism spectrum disorder or obsessive-compulsive disorder: An fMRI study (2019) · cites this paper as Chamberlain et al., 2007
Findings on SSRT in OCD and ASD using the stop-signal task have been mixed.
“Findings in OCD and ASD using this task have been mixed: increased SSRTs have been reported for individuals with OCD (Chamberlain et al., 2007; Kang et al., 2013; Mancini et al., 2018; Penadés et al., 2007; de Wit et al., 2012) and children with ASD (Geurts et al., 2004; Lemon et al., 2011), while other studies have found no differences (Adams and Jarrold, 2012; Chantiluke et al., 2015; Fan et al.”
From No evidence of differences in cognitive control in children with autism spectrum disorder or obsessive-compulsive disorder: An fMRI study (2019) · cites this paper as Chamberlain et al., 2007
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- Authors
- Chamberlain, S. R., Fineberg, N. A., Menzies, L. A., Blackwell, A. D., Bullmore, E. T., Robbins, T. W., & Sahakian, B. J.
- Affiliations
- University of Cambridge (GB)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2007-02
- Volume
- 164
- Issue
- 2
- Pages
- 335-338
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC1892796
- OpenAlex
- W2105875973
- Cited by
- 438
- References
- 19
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 30 · 2023: 17 · 2022: 28 · 2021: 31 · 2020: 20 · 2019: 28 · 2018: 19 · 2017: 22 · 2016: 18 · 2015: 33 · 2014: 30 · 2013: 29 · 2012: 24
- FWCI
- 22.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust (076244, 076274/Z04/Z)
- Medical Research Council
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- obsessive-compulsive disorder, cognitive flexibility, cognitive endophenotypes, motor inhibition, motor impulsivity, first-degree relatives, genetic susceptibility, inhibitory control, set-shifting, stop-signal reaction time, decision-making, genotype-phenotype correlation
- MeSH terms
- Adult, Cognition Disorders, Compulsive Behavior, Decision Making, Family Health, Female, Genetic Markers, Genotype, Humans, Inhibition, Psychological, Male, Motor Activity, Neuropsychological Tests, Obsessive-Compulsive Disorder, Pedigree, Phenotype, Psychomotor Performance, Reaction Time
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