Abstract
Our previous study suggested that the synapse-associated protein 97 (SAP97) gene rs3915512 polymorphism may influence neurocognition in schizophrenia patients. Neuroimaging studies have shown a possible association between cognitive function and brain activity/connectivity. Considering the poor understanding of whether the disease state and SAP97 rs3915512 polymorphism have interactive effects on brain activity/connectivity, 52 first-episode schizophrenia (FES) patients and 52 healthy controls were genotyped using blood DNA samples and underwent magnetic resonance imaging scanning. A two-way ANCOVA model was performed with rs3915512 genotypes and disease state as the between-subject factors. A significant disease × SAP97 interactive effect was found for the amplitude of low-frequency fluctuation (ALFF) in the right supplementary motor area, left rolandic opercularis area (ROC-L), and bilateral middle occipital gyrus (MOG). In addition, among auditory/visual-related brain areas, a significant interactive effect was found for resting-state functional connectivity (RSFC) between the MOG-L and bilateral superior temporal gyrus (STG) in the STG-L with ROC-R, right cuneus (Cu-R), left fusiform (Fu-L), and left lingual gyrus (LG-L). Positive correlations were found between ALFF in the ROC-L and motor speed scores, between RSFC in the STG-L and LG-L and between Brief Assessment of Cognition in Schizophrenia verbal memory scores in FES. The SAP97 rs3915512 polymorphism may affect neurocognitive function in patients with schizophrenia by changing the brain activity and connectivity of auditory/visual-related brain areas.
Highlights
Cognitive impairments mainly affect memory, attention, information integration, and execution (Harvey et al, 2001)
We found a significant genotype × disease interactive effect of amplitude of low-frequency fluctuation (ALFF) in the rolandic opercularis area (ROC-L), supplementary motor area (SMA-R) and bilateral middle occipital gyrus (MOG) in first-episode schizophrenia (FES)
A significant interactive effect was found of resting-state functional connectivity (RSFC) between the MOG-L and bilateral superior temporal gyrus (STG), STG-L, and several regions, including ROC-R, Cu-R, Fu-L, and lingual gyrus (LG-L), which are related to cognitive control (Kim et al, 2015)
Summary
Cognitive impairments mainly affect memory, attention, information integration, and execution (Harvey et al, 2001). Cognitive impairments occur in up to 85% of patients with schizophrenia and have been described as a core manifestation of schizophrenia (Mallet et al, 2020). The synapse-associated protein 97 (SAP97) gene, located at the schizophrenia susceptibility locus 3q29, was found to have reduced mRNA (Uezato et al, 2015) and protein expression in patients with schizophrenia (Toyooka et al, 2002). SAP97 can bind to a variety of potassium channels that have been shown to participate in the regulation of cognition function (Grube et al, 2011). SAP97 may change the cognition of schizophrenic patients by interacting with neurotransmitter receptors and potassium channels. Our previous study showed that schizophrenic patients with the SAP97 rs3915512 TT genotype have higher cognitive function scores than those carrying the A allele (Xu et al, 2018)
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