A Swedish National Prospective and Co-relative Study of School Achievement at Age 16, and Risk for Schizophrenia, Other Nonaffective Psychosis, and Bipolar Illness

Abstract

While cognitive ability is inversely associated with risk for schizophrenia (SZ), the association is less clear with other nonaffective psychoses (ONAP) and bipolar illness (BPI). Using national Swedish hospital registry data, we examined the prospective relationship between school achievement (SA) and development of SZ, ONAP, and BPI in 1800643 adolescents born 1972-1990. We used Cox proportional hazard and co-relative control models to predict onset of SZ, ONAP, and BPI from standardized SA scores at age 16. The hazard ratio (HRs; and 95% CIs) for first onset of SZ as a function of SA was 0.66 (0.64-0.68) for both sexes. For ONAP, the HRs equaled 0.66 (0.64-0.68) for males and 0.72 (0.70-0.75) for females. For BPI, parallel HRs were 0.81 (0.78-0.84) and 0.71 (0.70-0.73). The association between SA and risk was stronger in the lower vs the higher ranges of SA. In most analyses, moderate increases in risk were observed at the highest levels of SA, with the strongest evidence for females and risk of ONAP. Co-relative control analyses indicated that common genetic or familial-environmental effects only marginally confounded these associations. Consistent with prior studies, these results have 3 major implications for neurodevelopmental models: (1) adolescent cognitive deficits that increase risk are not the result of prodromal changes,( 2) individual specific environmental exposures are largely responsible for the association between low SA and psychosis risk, and (3) neurodevelopmental disturbances (as indicated by low SA) are not unique to SZ but also occur in ONAP and to a lesser degree BPI.

Keywords: Cognitive ability; bipolar illness; co-relative control analysis; other nonaffective psychoses; prospective risk; schizophrenia; school performance.

Fig. 1.

(a) Prospective risk for schizophrenia (± 95% CI) as a function of school achievement in both males and females. (b). Prospective risk for other nonaffective psychoses (±95% CI) as a function of school achievement separately in males and females. (c). Prospective risk for other bipolar illness (±95% CI) as a function of school achievement separately in males and females.

Fig. 2.

(a) Co-relative control analyses (±95% CI) for the association between school achievement and schizophrenia based on a linear HR model for males and females combined. The observed results for the general population and cousins, hsib (half siblings) and full siblings (sibs) discordant for SA are presented in blue. The associations predicted from a model fitted to the observed data in cousins, half siblings, full siblings, and monozygotic (MZ) twins are presented in red. (b). Co-relative control analyses (±95% CI) in females for the association between school achievement and other nonaffective psychoses based on a linear HR model for males and females combined. The observed results for the general population and cousins, hsib (half siblings) and full siblings (sibs) discordant for SA are presented in blue. The associations predicted from a model fitted to the observed data in cousins, half siblings, full siblings, and monozygotic (MZ) twins are presented in red. (c). Co-relative control analyses (±95% CI) in males for the association between school achievement and other nonaffective psychoses based on a linear HR model for males and females combined. The observed results for the general population and cousins, hsib (half siblings) and full siblings (sibs) discordant for SA are presented in blue. The associations predicted from a model fitted to the observed data in cousins, half siblings, full siblings, and monozygotic (MZ) twins are presented in red. (d). Co-relative control analyses (±95% CI) in females for the association between school achievement and bipolar illness based on a linear HR model for males and females combined. The observed results for the general population and cousins, hsib (half siblings) and full siblings (sibs) discordant for SA are presented in blue. The associations predicted from a model fitted to the observed data in cousins, half siblings, full siblings, and monozygotic (MZ) twins are presented in red. (e). Co-relative control analyses (±95% CI) in males for the association between school achievement and bipolar illness based on a linear HR model for males and females combined. The observed results for the general population and cousins, hsib (half-siblings) and full siblings (sibs) discordant for SA are presented in blue. The associations predicted from a model fitted to the observed data in cousins, half-siblings, full siblings, and monozygotic (MZ) twins are presented in red.