In this study, cognitive performance among FES, GHR, CHR and HC groups were investigated. We discovered that individuals in the FES, GHR, and CHR groups performed significantly poorer in most domains of the MATRICS Consensus Cognitive Battery (MCCB) compared to the HCs group. While cognitive impairment was evident in both GHR and CHR individuals, it was not as severe as in FES patients.
In our study, cognitive functioning in CHR individuals occupied an intermediate position between that of HCs and FES, which aligns with previous findings[14, 21]. CHR individuals underperformed compared to HCs across all MCCB domains except for visual learning, especially in areas of processing speed and attention/vigilance. Past meta-analyses have similarly observed CHR subjects lagging behind HCs in all MCCB cognitive domains, particularly in processing speed, attention/vigilance, and working memory[22]. The domains of cognitive deficits identified in the CHR group in our study echo those found in previous studies.
Several studies have compared cognitive impairment among the FES, CHR, and GHR groups[13, 14, 23]. In a previous study[13], a significant difference was found between CHR and FES groups in terms of the composite global score; GHR and FES groups showed similar levels of impairment, with GHR performing better than FES specifically in the domain of sustained attention. However, another study arrived at a different conclusion, suggesting that cognitive performance gradually decreased from HCs to first-degree relatives (FDR) and ultra-high-risk (UHR) individuals, ultimately reaching the FES group. This implies that cognitive functioning in the UHR group was intermediate between the FES and FDR groups. The disparity in conclusions between that study and ours may be attributed to differences in the cognitive assessment tools used, with our study employing the MCCB that measures a broader range of cognitive domains.
In our study, we identified impaired processing speed, attention/vigilance, working memory, and verbal learning in the GHR group, with the most significant impairment observed in the attention/vigilance domain. This finding aligns with previous studies that have suggested GHR individuals exhibit cognitive impairments similar to their affected siblings and demonstrate deficits of moderate severity compared to healthy controls[8, 15, 24, 25]. Previous research has reported larger effect sizes for measures of full-scale IQ, vocabulary, and single word reading tests, while measures of declarative memory, sustained attention, and working memory showed more modest effect sizes[8]. The differences observed in cognitive impairment domains between our study and previous studies may be attributed to variations in assessment tools used.
Among the three groups (FES, CHR, and GHR), processing speed and attention/vigilance were consistently impaired, with CHR and GHR individuals exhibiting milder impairments compared to FES. This finding is in line with some previous research studies[23, 26]. These results suggest that processing speed and attention/vigilance may hold promise as biomarkers for the early detection and severity assessment of schizophrenia. We hypothesize that genetic factors, current symptoms, or other unknown factors may influence these cognitive domains, and their impact on the indicators may accumulate over time. Hence, the heaviest impairment in these domains was observed in the FES group.
Interestingly, the severity of impairment in the reasoning/problem-solving domain was comparable between GHR and FES (with no statistically significant difference), while GHR exhibited milder impairment compared to FES (with a statistically significant difference). On the other hand, the severity of impairment in social recognition was similar between CHR and FES (with no statistically significant difference), while GHR displayed less impairment compared to FES (with no statistically significant difference). Previous studies have consistently reported impaired social cognition in CHR individuals[27]. Research on social cognition in GHR individuals is limited and inconsistent, but previous findings have indicated that social cognitive impairments are significantly associated with psychopathology in young relatives of individuals with schizophrenia[28]. Based on these findings, we speculate that social recognition may be more closely related to the current state of individuals, while reasoning/problem-solving may be more indicative of qualitative differences.
The utilization of the MCCB in this study helped standardize cognitive testing and domains, and the inclusion of unmedicated FES individuals helped minimize potential confounders. However, it is important to interpret the results with caution due to several limitations. Firstly, the sample size was relatively small, which may limit the generalizability of the findings. Secondly, the cross-sectional design of the study prevents the determination of a predictive neuropsychological marker for the transition to psychosis in at-risk individuals. Thirdly, the family history of 12 CHR individuals may serve as a confounding factor. Future analyses could benefit from including a larger sample size and incorporating clinical and genetically high-risk psychosis groups to enhance the robustness of the findings.