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Endophenotypes of executive functions in obsessive compulsive disorder? A meta-analysis in unaffected relatives

Zartaloudi, Eirinia; Laws, Keith R.b; Bramon, Elviraa

doi: 10.1097/YPG.0000000000000241
Review Article

Endophenotypes are mediator traits between genetic influences and clinical phenotypes. Meta-analyses have consistently shown modest impairments of executive functioning in obsessive compulsive disorder (OCD) patients compared to healthy controls. Similar deficits have also been reported in unaffected relatives of OCD patients, but have not been quantified. We conducted the first meta-analysis combining all studies investigating executive functioning in unaffected relatives of individuals with OCD to quantify any deficits. A search of Pubmed, Medline and PsychInfo databases identified 21 suitable papers comprising 707 unaffected relatives of OCD patients and 842 healthy controls. Effect sizes were calculated using random effects models. Unaffected relatives displayed a significant impairment in global executive functioning. Analyses of specific executive functioning subdomains revealed impairments in: planning, visuospatial working memory and verbal fluency. Deficits in executive functioning are promising endophenotypes for OCD. To identify further biomarkers of disease risk/resilience in OCD, we suggest examining specific executive functioning domains.

aDivision of Psychiatry, University College London, London

bSchool of Life and Medical Sciences, University of Hertfordshire, Hertfordshire, UK

Received 11 April 2019 Accepted 13 August 2019

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Correspondence to Eirini Zartaloudi, MSc, UCL Division of Psychiatry, 6th Floor Maple House, 149 Tottenham Court Road, London W1T 7NF, UK, Tel: +44 20 7679 6562; e-mail:

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