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The common variants implicated in microstructural abnormality of first episode and drug-naive patients with schizophrenia.

ABSTRACT: Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20?kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p?=?4.37?×?10^-8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400?kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p?=?1.89?×?10^-7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p?=?1.54?×?10^-17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.

SUBMITTER: Ren HY

PROVIDER: S-EPMC5603592 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Ren H Y HY Wang Q Q Lei W W Zhang C C CC Li Y F YF Li X J XJ Li M L ML Deng W W Huang C H CH Du F F Zhao L S LS Wang Y C YC Ma X H XH Hu X X Li T T

Scientific reports 20170918 1

Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA ...[more]

PMID: 28924203

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Project description:Convergent evidence has suggested a significant effect of antipsychotic exposure on brain structure and function in patients with schizophrenia, yet the characteristics of favorable treatment outcome remains largely unknown. In this work, we aimed to examine how large-scale brain networks are modulated by antipsychotic treatment, and whether the longitudinal changes could track the improvements of psychopathologic scores. Thirty-four patients with first-episode drug-naïve schizophrenia and 28 matched healthy controls were recruited at baseline from Shanghai Mental Health Center. After 8 weeks of antipsychotic treatment, 24 patients were re-scanned. Through a systematical dynamic functional connectivity (dFC) analysis, we investigated the schizophrenia-related intrinsic alterations of dFC at baseline, followed by a longitudinal study to examine the influence of antipsychotic treatment on these abnormalities by comparing patients at baseline and follow-up. A structural connectivity (SC) association analysis was further carried out to investigate longitudinal anatomical changes that underpin the alterations of dFC. We found a significant symptomatic improvement-related increase in the occurrence of a dFC state characterized by stronger inter-network integration. Furthermore, symptom reduction was correlated with increased FC variability in a unique connectomic signature, particularly in the connections within the default mode network and between the auditory, cognitive control, and cerebellar network to other networks. Additionally, we observed that the SC between the superior frontal gyrus and medial prefrontal cortex was decreased after treatment, suggesting a relaxation of normal constraints on dFC. Taken together, these findings provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network. Moreover, our identified neuroimaging markers tied to the neurobiology of schizophrenia could be used as potential indicators in predicting the treatment outcome of antipsychotics.

Dataset Information

The common variants implicated in microstructural abnormality of first episode and drug-naive patients with schizophrenia.

Publications

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia.

Similar Datasets

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