Abstract
Background: Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo), has been consistently reported in patients with schizophrenia (SCZ) and their unaffected siblings. To date, little is known about the genetic influences affecting the spontaneous neuronal activity in SCZ. DISC1, a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of DISC1 variations on the regional spontaneous neuronal activity in SCZ.Methods: Resting-state fMRI data were obtained from 28 SCZ patients and 21 healthy controls (HC) for ReHo analysis. Six single nucleotide polymorphisms (SNPs) of DISC1 gene were genotyped using the PCR and direct sequencing.Results: Significant diagnosis × genotype interactions were noted for three SNPs (rs821616, rs821617, and rs2738880). For rs821617, the interactions were localized to the precuneus, basal ganglia and pre-/post-central regions. Significant interactive effects were identified at the temporal and post-central gyri for rs821616 (Ser704Cys) and the inferior temporal gyrus for rs2738880. Furthermore, post-hoc analysis revealed that the DISC1 variations on these SNPs exerted different influences on ReHo between SCZ patients and HC.Conclusion: To our knowledge this is the first study to unpick the influence of DISC1 variations on spontaneous neuronal activity in SCZ; Given the emerging evidence that ReHo is a stable inheritable phenotype for schizophrenia, our findings suggest the DISC1 variations are possibly an inheritable source for the altered ReHo in this disorder.
Highlights
Schizophrenia (SCZ) is a severe and devastating neurodevelopmental disorder with a wide range of clinical clusters and fits a complex mode of inheritance with thousands of genetic variations with small effects [1, 2]
Since our prior work by Gong et al has identified 6 DISC1 single nucleotide polymorphisms (SNPs) that are consistently associated with resting-state functional alterations in schizophrenia patients, this study focused on the contribution of these SNPs to the abnormality of regional homogeneity at rest in this severe mental disorder
No significant differences were found between SCH and healthy controls (HC) group in terms of gender, education, except for the age (P < 0.05) which was entered as the covariate into further fMRI data analysis
Summary
Schizophrenia (SCZ) is a severe and devastating neurodevelopmental disorder with a wide range of clinical clusters and fits a complex mode of inheritance with thousands of genetic variations with small effects [1, 2]. Researches using the ReHo have consistently showed that the incoherent neuronal activity was shared by SCZ patients and their healthy siblings [11, 16, 17], implying the incoherence of spontaneous neuronal activity in SCZ is highly associated with inheritable factors. Owing to the current literatures that few studies, up to date, have examined these inheritable factors for ReHo, the neural mechanism by which the genetic mutants contribute to the altered spontaneous neuronal activity in SCZ remains unknown. Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo), has been consistently reported in patients with schizophrenia (SCZ) and their unaffected siblings. DISC1, a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of DISC1 variations on the regional spontaneous neuronal activity in SCZ
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