Impairment of executive function and attention predicts onset of affective disorder in healthy high-risk twins

J Clin Psychiatry. 2013 Aug;74(8):e747-53. doi: 10.4088/JCP.12m08258.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adult
  • Age of Onset
  • Anxiety Disorders / diagnosis*
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / psychology
  • Attention*
  • Child
  • Denmark
  • Diseases in Twins / diagnosis*
  • Diseases in Twins / genetics*
  • Diseases in Twins / psychology
  • Executive Function*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Interview, Psychological
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mood Disorders / diagnosis*
  • Mood Disorders / genetics*
  • Mood Disorders / psychology
  • Neuropsychological Tests
  • Predictive Value of Tests
  • Registries
  • Risk
  • Trail Making Test
  • Twins, Dizygotic / genetics
  • Twins, Dizygotic / psychology
  • Twins, Monozygotic / genetics
  • Twins, Monozygotic / psychology