Effects of DISC1 Polymorphisms on Resting-State Spontaneous Neuronal Activity in the Early-Stage of Schizophrenia

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.

Abnormal network homogeneity of default-mode network and its relationships with clinical symptoms in antipsychotic-naïve first-diagnosis schizophrenia

“…Nevertheless, research comprising functional or structural MRI using different analyses, such as global-brain FC ( Zhao et al, 2022 ), the dynamic amplitude of low-frequency fluctuation ( Wang et al, 2021 ), full- and short-range strength of FC ( Miao et al, 2020 ), and Trace ( Lee et al, 2016 ), have observed aberrant ITG in patients with schizophrenia, which is associated with psychotic ( Lee et al, 2016 ) and cognitive symptoms ( Lee et al, 2016 ) and might predict the response to an antipsychotic drug after 8 weeks ( Zhu et al, 2018 ). Previous studies also showed that both patients with schizophrenia and their unaffected siblings shared similar alterations in the ITG ( Liu H. et al, 2012 ; Zhu et al, 2018 ), and the neural activity of ITG was regulated by regulating by the Disrupted-in-Schizophrenia-1 gene ( Gou et al, 2018 ), suggesting that the ITG might be a potential biomarker of endophenotype for schizophrenia. Zhu et al (2020) stated that the right ITG might show unique abnormalities in patients with schizophrenia compared with those with bipolar disorder and attention-deficit/hyperactivity disorder.…”

Disrupted local functional connectivity in schizophrenia: An updated and extended meta-analysis

“…As shown in Fig. 1, our search strategy initially identified 1816 studies, of which 18 studies were eligible for meta-analysis including a total of 652 patients with schizophrenia and 596 healthy controls [10][11][12][13][14][15][24][25][26][27][46][47][48][49][50][51][52][53] . Among these studies, three studies were longitudinal designs, and we only included the results of between-group comparison using baseline data 13,46,51 .…”

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis

“…After initially removing the duplicates and browsing the title and summary, we found that 28 studies met the inclusion criteria, furthermore, after a detailed review of the full text, a total of 13 studies met the inclusion criteria. 8,9,11,12,[22][23][24][25][26][27][28][29][30] Figure 1 illustrates the identification and exclusion flow chart for the study. The included research reported ReHo differences in 511 schizophrenia (193 with FES and 318 with chronic schizophrenia), and compared with 452 HCs.…”

“…38 Both Increased ReHo and decreased ReHo were reported in the insula in patients with schizophrenia, 11,39 while some other studies showed negative results. 29,40 The reason may be attributed to the heterogeneity of the sample, statistical methods and sample size. A multicenter structural magnetic resonance meta-analysis showed significant thinning of the insula cortex and a significant correlation with drug dose, disease duration and age of onset.…”