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Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks.

ABSTRACT: Recently, an increasing body of evidence suggests that developmental abnormalities related to schizophrenia may occur as early as the neonatal stage. Impairments of brain gray matter and wiring problems of axonal fibers are commonly suspected to be responsible for the disconnection hypothesis in schizophrenia adults, but significantly less is known in neonates. In this study, we investigated 26 neonates who were at genetic risk for schizophrenia and 26 demographically matched healthy neonates using both morphological and white matter networks to examine possible brain connectivity abnormalities. The results showed that both populations exhibited small-world network topology. Morphological network analysis indicated that the brain structural associations of the high-risk neonates tended to have globally lower efficiency, longer connection distance, and less number of hub nodes and edges with relatively higher betweenness. Subgroup analysis showed that male neonates were significantly disease-affected, while the female neonates were not. White matter network analysis, however, showed that the fiber networks were globally unaffected, although several subcortical-cortical connections had significantly less number of fibers in high-risk neonates. This study provides new lines of evidence in support of the disconnection hypothesis, reinforcing the notion that the genetic risk of schizophrenia induces alterations in both gray matter structural associations and white matter connectivity.

SUBMITTER: Shi F

PROVIDER: S-EPMC3408572 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks.

Shi Feng F Yap Pew-Thian PT Gao Wei W Lin Weili W Gilmore John H JH Shen Dinggang D

NeuroImage 20120519 3

Recently, an increasing body of evidence suggests that developmental abnormalities related to schizophrenia may occur as early as the neonatal stage. Impairments of brain gray matter and wiring problems of axonal fibers are commonly suspected to be responsible for the disconnection hypothesis in schizophrenia adults, but significantly less is known in neonates. In this study, we investigated 26 neonates who were at genetic risk for schizophrenia and 26 demographically matched healthy neonates us ...[more]

PMID: 22613620

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Project description:Several studies have produced extensive evidence on white matter abnormalities in schizophrenia (SZ). However, optimum consistency and reproducibility have not been achieved, and reported low white matter tract integrity in patients with SZ varies between studies. A whole-brain imaging study with a large sample size is needed. This study aimed to investigate white matter integrity in the corpus callosum and connections between regions of interests (ROIs) in the same hemisphere in 122 patients with SZ and 129 healthy controls with public neuroimaging data from SchizConnect. For each diffusion-weighted image (DWI), two-tensor full-brain tractography was performed; DWIs were parcellated by processing and registering T1 images with FreeSurfer and Advanced Normalization Tools. White matter query language was used to extract white matter fiber tracts. We evaluated group differences in means of diffusion measures between the patients and controls, and correlations of diffusion measures with the severity of clinical symptoms and cognitive impairment in the patients using the Positive and Negative Syndrome Scale (PANSS), a letter-number sequencing (LNS) test, vocabulary test, letter fluency test, category fluency test, and trail-making test, part A. To correct for multiple comparisons, a false discovery rate of q < 0.05 was applied. In patients with SZ, we observed significant radial diffusivity (RD) and trace (TR) increases in left thalamo-occipital tracts and the right uncinate fascicle, and a significant RD increase in the right middle longitudinal fascicle (MDLF) and the right superior longitudinal fascicle ii. Correlations were present between TR of left thalamo-occipital tracts, and the letter fluency test and the LNS test, and RD in the right MDLF and PANSS positive subscale score. However, these correlations were not significant after correction for multiple comparisons. These results indicated widespread white matter fiber tract abnormalities in patients with SZ, contributing to SZ pathophysiology.

Dataset Information

Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks.

Publications

Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks.

Similar Datasets

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