ABSTRACT
The ZNF804A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity (RSFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) in both schizophrenic patients and healthy controls. The homozygous ZNF804A rs1344706 genotype (AA) conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC (F(2,165) = 13.43, P < 0.001). The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804A rs1344706 on hippocampal-prefrontal RSFC associated with schizophrenia.
Subject(s)
Adult , Female , Humans , Male , Young Adult , Analysis of Variance , Functional Laterality , Genetics , Genotype , Hippocampus , Diagnostic Imaging , Image Processing, Computer-Assisted , Kruppel-Like Transcription Factors , Genetics , Magnetic Resonance Imaging , Neural Pathways , Diagnostic Imaging , Neuropsychological Tests , Oxygen , Blood , Polymorphism, Single Nucleotide , Genetics , Prefrontal Cortex , Diagnostic Imaging , Psychiatric Status Rating Scales , Schizophrenia , Diagnostic Imaging , Genetics , Severity of Illness IndexABSTRACT
Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume (GMV) reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex (rMFC, including the anterior cingulate cortex) in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale (PANSS), and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential processing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symptoms of schizophrenia and for making clinical decisions.