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Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.
Methods
First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.
Results
The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.
Conclusions
The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.
Chapter 1 aims to correct popular misinformation and summarizes how intelligence is defined and measured for scientific research. Some of the validity data will surprise you. For example, childhood IQ scores predict adult mortality.
Considering the continuing interest of the scientific community and the public in the genetic bases of intelligence, in this chapter we highlight three facets of the numerous studies in this broad area: (1) the trajectory of studies that have sought to elucidate the etiology of intelligence; (2) the relevance of the selected phenotype; and (3) the consequence of the chosen genetic mechanism. The use of three main approaches to the study of the genetic bases of intelligence (the linkage studies focused on heritability of the phenotypic trait, hypothesis-driven candidate region and gene studies, and genome-wide association studies) has resulted in a list of about 150 genes apparently associated with intelligence, but the discrepancy between the heritability estimates obtained in quantitative versus molecular genetic studies persists. One explanation of this discrepancy relates to the heterogeneity of the phenotypes often used in quantitative versus molecular genetic studies. The other states that, in addition to the genetic mechanism sampled by genome-wide association studies (i.e., the common variance-based mechanism), there may be other genetic mechanisms that influence individual differences in intelligence, in particular, epigenetic mechanisms. Their consideration may become a course-changing innovation for understanding the genetic bases of intelligence and providing a window onto the diversity of human abilities.
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