We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

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

Kenneth S. Kendler, MD1,2,3; Henrik Ohlsson, PhD4; Briana Mezuk, PhD5; Jan O. Sundquist, MD, PhD4; Kristina Sundquist, MD, PhD4
[+] Author Affiliations
1Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond
2Department of Psychiatry, Virginia Commonwealth University, Richmond
3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond
4Center for Primary Health Care Research, Lund University, Malmö, Sweden
5Division of Epidemiology, Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond
JAMA Psychiatry. 2016;73(5):465-471. doi:10.1001/jamapsychiatry.2016.0053.
Text Size: A A A
Published online

Importance  Proposal of an innovative approach to clarify the mechanism through which poor cognitive performance in adolescence impacts risk for schizophrenia (SZ).

Objective  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).

Design, Setting, and Participants  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.

Main Outcomes and Measures  Diagnoses of SZ or BPI in the Swedish Hospital Discharge Register and the Swedish Outpatient Register.

Results  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.

Conclusions and Relevance  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.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Hazard Ratio (95% CI) for First Registration for Schizophrenia in 996 889 Swedish Individuals Born 1972 to 1990 as a Function of Their School Achievement at Age 16 Years and Their Familial Cognitive Aptitude Calculated From School Achievement in Full Siblings and Cousins and Educational Status in Parents

Not all possible combinations are presented because some potential groups (eg, familial cognitive aptitude of +2 SDs and school achievement of −1 or −2 SDs) were too rare to calculate with confidence. For precise data and 95% CIs for all values in this figure, see the eTable in the Supplement.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Mean (95% CI) School Achievement (Assessed at Age 16 Years) or IQ (Assessed at Ages 18-20 Years) for Individuals Who Go On to Develop Schizophrenia or Bipolar Illness and Matched Controls and Their Full Siblings

aDifferent from control siblings (P < .001).

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections