Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome

Abstract

22q11.2 deletion syndrome (22q11DS) represents a homogeneous model of schizophrenia particularly suitable for the search of neural biomarkers of psychosis. Impairments in structural connectivity related to the presence of psychotic symptoms have been reported in patients with 22q11DS. However, the relationships between connectivity changes in patients with different symptomatic profiles are still largely unknown and warrant further investigations. In this study, we used structural connectivity to discriminate patients with 22q11DS with (N = 31) and without (N = 31) attenuated positive psychotic symptoms. Different structural connectivity measures were used, including the number of streamlines connecting pairs of brain regions, graph theoretical measures, and diffusion measures. We used univariate group comparisons as well as predictive multivariate approaches. The univariate comparison of connectivity measures between patients with or without attenuated positive psychotic symptoms did not give significant results. However, the multivariate prediction revealed that altered structural network architecture discriminates patient subtypes (accuracy = 67.7%). Among the regions contributing to the classification we found the anterior cingulate cortex, which is known to be associated to the presence of psychotic symptoms in patients with 22q11DS. Furthermore, a significant discrimination (accuracy = 64%) was obtained with fractional anisotropy and radial diffusivity in the left inferior longitudinal fasciculus and the right cingulate gyrus. Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies.

Keywords: Anterior cingulate cortex; Diffusion tensor imaging; Graph theory; Limbic system; Multivariate; Psychosis.

Fig. 1

Overview of the data processing and analysis.

Fig. 2

Accuracy plot for the number of streamlines. The blue line indicates the accuracy, the two red lines indicate the upper and lower confidence intervals. No significant accuracy was achieved at any features intervals. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Accuracy plot of the discrimination analysis using graph theory measures computed on the weighted graph. Classification results when using all the graph theory measures and feature selection. The blue line indicates the accuracy, the two red lines indicate the upper and lower confidence intervals. No significant accuracy was achieved at any features intervals. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Results of the discrimination analysis using graph theory measures computed on the binary graph. On the top, the accuracy plot displays the maximum significant accuracy achieved with the five best features. The blue line indicates the accuracy and the red lines indicate the upper and lower confidence intervals. The brain maps show the regions where the betweenness centrality and the clustering coefficient contributed to the discrimination. The amygdala is not showed in the cortical maps as it is a sub-cortical region. The boxplots show the betweenness centrality and the clustering coefficient values for the corresponding regions. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Results of the discrimination analysis using diffusion measures. In the first row, accuracy is reported for the multivariate analysis without features selection. In the second row, accuracy plots display the results when performing feature selection. The brain maps in the last row show the tracts that significantly discriminated patients with and without mild to attenuated psychotic symptoms. ILF = inferior longitudinal fasciculus, CG = cingulate gyrus, FA = Fractional Anisotropy, AD = axial diffusivity, RD = radial diffusivity.