Impaired cognitive flexibility and motor inhibition in unaffected first-degree relatives of patients with obsessive-compulsive disorder.
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.


METHODS
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.
Chamberlain
Samuel R
SR
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Box 189, Cambridge, CB2 2QQ UK. src33@cam.ac.uk
Fineberg
Naomi A
NA
Menzies
Lara A
LA
Blackwell
Andrew D
AD
Bullmore
Edward T
ET
Robbins
Trevor W
TW
Sahakian
Barbara J
BJ
D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics; D003192:Compulsive Behavior / Q000175:diagnosis / Q000235:genetics; D003657:Decision Making; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D010375:Pedigree; D010641:Phenotype; D011597:Psychomotor Performance; D011930:Reaction Time / Q000502:physiology*
D005819:Genetic Markers