Aberrant perfusion and its connectivity within default mode network of first-episode drug-naïve schizophrenia patients and their unaffected first-degree relatives

Abstract

Neural substrates behind schizophrenia (SZ) and its heritability mediated by brain function are largely unknown. Cerebral blood flow (CBF), as a biomarker of activation in the brain, reflects the neuronal metabolism, and is promisingly used to detect cerebral alteration thereby shedding light on the features of individuals at high genetic risk. We performed a cross-sectional functional magnetic resonance imaging (MRI) study enrolling 45 first-episode drug-naïve patients with SZ, 32 unaffected first-degree relatives of these patients, and 51 healthy controls (HCs). We examined CBF, CBF connectivity, and CBF topological properties. SZ patients showed increased CBF in the left medial superior frontal gyrus and right precuneus compared with HCs, and decreased CBF in the left middle temporal gyrus compared with their relatives. Furthermore, unaffected relatives revealed higher level of CBF pronounced in regions within default mode network (DMN). Both SZ patients and their relatives exhibited dysconnectivity patterns. Notably, as for the network properties, unaffected relatives were with an intermediate level between SZ patients and HCs in the local efficiency and global efficiency. Our findings demonstrate the aberrant CBF of areas within DMN and the CBF connectivity pattern might be a familial feature in the brain of first-episode SZ patients and their relatives.

Figure 1

Comparisons of CBF among SZ patients, their unaffected relatives and HCs using ANOVA. The coordinate of each slice is marked in the upper-left. The color bar on the right indicates the F values. Brain regions with difference in CBF are marked by white arrows. MCG, middle cingulate gyrus; MTG, middle temporal gyrus; SFG, superior frontal gyrus; SOG, superior occipital gyrus; STG, superior temporal gyrus.

Figure 2

The CBF connectivity matrix obtained by calculating Pearson’s correlation between regional CBF across subjects. Numbers on the left and lower sides of each matrix refer to the corresponding brain regions in AAL template. The color bar indicates the Pearson correlation coefficients.

Figure 3

The CBF networks showing connections with correlation coefficient value larger than 0.6 or less than −0.6. Connectivity pattern of each group is in line with the matrix in Fig. 2. Red balls represent the 90 brain regions in AAL atlas. Line color indicates the positive (red) or negative (blue) coefficient.

Figure 4

Global network properties as function of sparsity degree. The characteristic path length, clustering index, local efficiency, and global efficiency decrease as the sparsity degree increases. The error bar represents standard deviation. SZ, schizophrenia (red line); REL, relatives (green line); HCs, healthy controls (blue line).