Abstract
Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.2 deletion syndrome (22q11.2DS). Cerebral MRIs were acquired for 46 patients and 48 age and gender matched controls (aged 6–26, respectively mean age = 15.20 ± 4.53 and 15.28 ± 4.35 years old). Using the Connectome mapper pipeline (connectomics.org) that combines structural and diffusion MRI, we created a whole brain network for each individual. Graph theory was used to quantify the global and local properties of the brain network organization for each participant. A global degree loss of 6% was found in patients' networks along with an increased Characteristic Path Length. After identifying and comparing hubs, a significant loss of degree in patients' hubs was found in 58% of the hubs. Based on Allen's brain network model for hallucinations, we explored the association between local efficiency and symptom severity. Negative correlations were found in the Broca's area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014). In line with the dysconnection findings in schizophrenia, our results provide preliminary evidence for a targeted alteration in the brain network hubs' organization in individuals with a genetic risk for schizophrenia. The study of specific disorganization in language, speech and thought regulation networks sharing similar network properties may help to understand their role in the hallucination mechanism.
Highlights
22q11.2 deletion syndrome (22q11.2DS), known as velocardio-facial syndrome (Shprintzen et al, 1978), is a wellestablished neurogenetic model for studying the pathogenesis of schizophrenia (Bassett and Chow, 1999)
Based on Allen’s brain network model for hallucinations, we explored the association between local efficiency and symptom severity
Negative correlations were found in the Broca’s area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014)
Summary
22q11.2 deletion syndrome (22q11.2DS), known as velocardio-facial syndrome (Shprintzen et al, 1978), is a wellestablished neurogenetic model for studying the pathogenesis of schizophrenia (Bassett and Chow, 1999). Following Latora and Marchiori’s conception of global and local efficiency measuring how well information is exchanged over the network (Latora and Marchiori, 2001), Wang et al (2011) demonstrated that individuals with schizophrenia have a reduced global efficiency [reduced after controlling for the effect of age, gender and brain size (Wang et al, 2011)] It remains unclear whether the network alterations are caused by the emergence of the schizophrenia disorder or if there is a predetermined network configuration that acts as a vulnerability factor for the later development of schizophrenia. Lower global efficiency and longer path length has been related to higher score on the negative PANSS scale (Yu et al, 2011a,b) The purpose of this present work is to study the global and local network features in a population at high genetic risk for schizophrenia (22q11.2DS) by focusing on the hierarchical structure of the brain network (hub topological configuration). According to Allen’s model of brain regions involved in hallucinations (Allen et al, 2008), we suggest that the topological connectivity of the following regions—DLPFC, dorsal anterior cingulate, Broca’s area, ventral anterior cingulate, orbitofrontal gyrus, and STG—will be associated with the severity of hallucinations in schizophrenia
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