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Original Research

Impairment of Executive Function and Attention Predicts Onset of Affective Disorder in Healthy High-Risk Twins

Maj Vinberg, MD, PhD; Kamilla W. Miskowiak, PhD; and Lars Vedel Kessing, MD, DMSc

Published: August 15, 2013

Article Abstract

Objective: To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk.

Method: In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high- and low-risk twins, respectively) were identified through nationwide registers and assessed at baseline using the Schedules for Clinical Assessment in Neuropsychiatry, the 17-item Hamilton Depression Rating Scale (HDRS), and the cognitive tests Trail Making Test Parts A and B, the Stroop test, and the Cambridge Cognitive Examination-Revised (CAMCOR). Participants were followed longitudinally at 6-month intervals for up to 9 years and finally reassessed with a personal interview to obtain information on whether they had developed psychiatric illness. The study was conducted between 2003 and 2012.

Results: 36 participants (15.4%) developed psychiatric disorder, mainly affective and anxiety disorders (31 diagnoses) (ICD-10). Onset was predicted by decreased executive function as reflected by performance on the Trail Making Test A – B (hazard ratio [HR] = 1.02; 95% CI, 1.00-1.03) when adjusted for sex, age, years of education and HDRS score at baseline. Reduced global cognitive function as indicated by a lower CAMCOR score at baseline showed a trend toward an association with subsequent illness onset (P = .08). With regard to the 5 CAMCOR subscales, lower scores on attention (HR = 0.71; 95%, CI, 0.54-0.94) and language (HR = 0.76; 95% CI, 0.58-0.99) were significantly associated with subsequent illness onset.

Conclusions: Among healthy individuals at heritable risk for affective disorder, discrete cognitive deficits, especially within executive function and attention, seem to predict subsequent onset of affective illness.

J Clin Psychiatry 2013;74(8):e747-e753

Submitted: October 30, 2012; accepted February 25, 2013 (doi:10.4088/JCP.12m08258).

Corresponding author: Maj Vinberg, MD, PhD, Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark (

Volume: 74

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