Abstract
Schizophrenia is a multifactorial disease associated with widespread cognitive impairment. Although cognitive deficits are one of the factors most strongly associated with functional impairment in schizophrenia (SZ), current treatment strategies hardly tackle these impairments. To develop more efficient treatment strategies in patients, a better understanding of their pathogenesis is needed. Recent progress in genetics, driven by large genome-wide association studies (GWAS) and the use of polygenic risk scores (PRS), has provided new insights about the genetic architecture of complex human traits, including cognition and SZ. Here, we review the recent findings examining the genetic links between SZ and cognitive functions in population-based samples as well as in participants with SZ. The performed meta-analysis showed a negative correlation between the polygenetic risk score of schizophrenia and global cognition (p < 0.001) when the samples rely on general and healthy participants, while no significant correlation was detected when the three studies devoted to schizophrenia patients were meta-analysed (p > 0.05). Our review and meta-analysis therefore argues against universal pleiotropy for schizophrenia alleles and cognition, since cognition in SZ patients would be underpinned by the same genetic factors than in the general population, and substantially independent of common variant liability to the disorder.
Highlights
Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction [44], suggesting that cognitive deficit is reliably linked with inherited risk for schizophrenia and that it predates the diagnosis [17]
A study found a higher propensity to succeed in the “English school level” and less attention to detail in adolescents with high polygenic risk score (PRS) [51], which could be in line with the propensity for creativity predicted by SZ PRS [52]
The authors hypothesized that the discrepancy between the cognitive and educational results is mediated by the age of the participants—if schizophrenia genes are detrimental to cognitive functioning only later in life, they may have differential effects on educational attainment, and the cognitive tests
Summary
Cognitive functioning is positively associated with greater longevity and less physical and psychiatric morbidity, and negatively associated with several quantitative disease risk factors and indices [1]. Higher general cognitive function in childhood is predictive of lower self-reported psychological distress decades later [2]. This association between cognitive function and psychological well-being extends to severe psychiatric conditions. Lower scores on standard tests of intelligence have consistently been associated with an increased risk of schizophrenia [4]. It is not clear whether schizophrenia affects cognitive functioning or vice versa, or whether both are influenced by some common factors. The associations between cognitive functioning and schizophrenia may, in part, reflect shared genetic influences
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