title: Observed Cognitive Performance and Deviation From Familial Cognitive Aptitude at Age 16 Years and Ages 18 to 20 Years and Risk for Schizophrenia and Bipolar Illness in a Swedish National Sample.
abstract: Proposal of an innovative approach to clarify the mechanism through which poor cognitive performance in adolescence impacts risk for schizophrenia (SZ).
  
  
  
  To determine whether the developmental processes that predispose to SZ are better reflected by the observed cognitive performance in adolescence or the deviation of that performance from the individual's familial cognitive aptitude (FCA).
  
  
  
  A prospective cohort design. Risk for SZ and bipolar illness (BPI) are predicted by school achievement (SA) at age 16 years and IQ at ages 18 to 20 years and the deviation of that performance from an individual's FCA. Familial cognitive aptitude is calculated from the SA, IQ, and educational attainment in biological relatives.
  
  
  
  Diagnoses of SZ or BPI in the Swedish Hospital Discharge Register and the Swedish Outpatient Register.
  
  
  
  Participants were 996 886 individuals with recorded SA and 106 187 individuals with recorded IQ born in Sweden between January 1, 1972, and December 31, 1990, with sufficient numbers of biological relatives to calculate their FCA. The first cohort is 48.7% female, and the second is all male. Risk for SZ was strongly predicted by the deviation of SA from the FCA (hazard ratio [HR], 0.56; 95% CI, 0.49-0.63) but not with the observed SA (HR, 1.01; 95% CI, 0.91-1.13). Similar results were obtained for IQ (HR, 0.53; 95% CI, 0.37-0.77 for the deviation from the FCA and HR, 1.07; 95% CI, 0.78-1.46 for the observed IQ). After matching SZ and control probands on cognitive performance, the siblings of the SZ probands had SA and IQs that did not differ from population means and were significantly higher in cognitive performance than for the siblings of control probands. Correlations in SA and IQs between the pre-SZ probands and their siblings were significantly lower than those observed between the matched control probands and their siblings. Risk for BPI was more weakly predicted by deviations from the FCA. No differences were found in the SA and IQs of siblings of BPI vs matched control probands.
  
  
  
  The neurodevelopmental processes that predispose to SZ are not well reflected by cognitive performance per se but rather are much better indexed by the deviation in cognitive ability from that expected from an individual's FCA. The lowered cognitive performance in the pre-SZ probands appears to arise from qualitative developmental impairments rather than an unlucky combination of the genetic and environmental risk factors widely distributed within their family.
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond2Department of Psychiatry, Virginia Commonwealth University, Richmond3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richm.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ohlsson
authors.affiliation: Division of Epidemiology, Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond.
authors.forename: Briana
authors.initials: B
authors.lastname: Mezuk
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Sundquist
authors.affiliation: Center for Primary Health Care Research, Lund University, Malmö, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
mesh_terms: D000124:Achievement; D000293:Adolescent; D001076:Aptitude; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*; D012565:Schizophrenic Psychology; D013223:Statistics as Topic; D013548:Sweden; D055815:Young Adult