Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express the same deviant patterns of resting state EEG microstates: A candidate endophenotype of schizophrenia

Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80. ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia. © 2015 The Authors.

Reduced Fronto-Temporal and Limbic Connectivity in the 22q11.2 Deletion Syndrome: Vulnerability Markers for Developing Schizophrenia?

Leila Cammoun, Marie Schaer, Jean-Philippe Thiran

The 22q11.2 deletion syndrome (22q11DS) is a widely recognized genetic model allowing the study of neuroanatomicalvbiomarkers that underlie the risk for developing schizophrenia. Recent advances in magnetic resonance image analysesvenable the examination of structural connectivity integrity, scarcely used in the 22q11DS field. This framework potentiallyvprovides evidence for the disconnectivity hypothesis of schizophrenia in this high-risk population. In the present study, wevquantify the whole brain white matter connections in 22q11DS using deterministic tractography. Diffusion Tensor Imaging was acquired in 30 affected patients and 30 age- and gender-matched healthy participants. The Human Connectome technique was applied to register white matter streamlines with cortical anatomy. The number of fibers (streamlines) was used as a measure of connectivity for comparison between groups at the global, lobar and regional level. All statistics were corrected for age and gender. Results showed a 10% reduction of the total number of fibers in patients compared to controls. After correcting for this global reduction, preserved connectivity was found within the right frontal and right parietal lobes. The relative increase in the number of fibers was located mainly in the right hemisphere. Conversely, an excessive reduction of connectivity was observed within and between limbic structures. Finally, a disproportionate reduction was shown at the level of fibers connecting the left fronto-temporal regions. We could therefore speculate that the observed disruption to fronto-temporal connectivity in individuals at risk of schizophrenia implies that fronto-temporal disconnectivity, frequently implicated in the pathogenesis of schizophrenia, could precede the onset of symptoms and, as such, constitutes a biomarker of the vulnerability to develop psychosis. On the contrary, connectivity alterations in the limbic lobe play a role in a wide range of psychiatric disorders and therefore seem to be less specific in defining schizophrenia.

Public Library of Science2013

Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis

Fikret Isik Karahanoglu, Jonas Richiardi, Marie Schaer, Maude Schneider, Dimitri Nestor Alice Van De Ville

The 22q11.2 deletion syndrome (22q11DS) is associated with cognitive impairments and a 41% risk of developing schizophrenia. While several studies performed on patients with 22q11DS showed the presence of abnormal functional connectivity in this syndrome, how these alterations affect large-scale network organization is still unknown. Here we performed a network modularity analysis on whole-brain functional connectomes derived from the resting-state fMRI of 40 patients with 22q11DS and 41 healthy control participants, aged between 9 and 30 years old. We then split the sample at 18 years old to obtain two age subgroups and repeated the modularity analyses. We found alterations of modular communities affecting the visuo-spatial network and the anterior cingulate cortex (ACC) in both age groups. These results corroborate previous structural and functional studies in 22q11DS that showed early impairment of visuo-spatial processing regions. Furthermore, as ACC has been linked to the development of psychotic symptoms in 22q11DS, the early impairment of its functional connectivity provide further support that ACC alterations may provide potential biomarkers for an increased risk of schizophrenia. Finally, we found an abnormal modularity partition of the dorsolateral prefrontal cortex (DLPFC) only in adults with 22q11DS, suggesting the presence of an abnormal development of functional network communities during adolescence in 22q11DS. (C) 2016 Elsevier Ltd. All rights reserved.

Elsevier Masson2016

Electrophysiological correlates of visual backward masking in the schizophrenia continuum

Ophélie Gladys Favrod

In visual backward masking (VBM), a target is followed by a mask. Over the past decade, a VBM task, called the Shine-Through paradigm (ST), has been shown to be a very sensitive endophenotype of schizophrenia. In the present thesis, the electrophysiological correlates (EEG) of this endophenotype are investigated. Patients with schizophrenia show strongly reduced amplitudes of the Global Field Power (GFP, standard deviation across all electrodes of the EEG) 200 ms after target onset. Here, I show, first, that patients with first episode psychosis also have masking deficits and that the associated EEG amplitudes are between those of controls and patients with schizophrenia. In detail, when the task is challenging the neural correlates are similar to patients with schizophrenia and when the task is easy the neural correlates are similar to controls. This result suggests that patients with first episode psychosis are in an intermediate state where the disease is not fully developed yet. In addition, the neural signature is stable over at least one year meaning that the fully developed deficits must occur over durations longer than one year. Second, I show that healthy participants with high schizotypal traits, in particular scoring high in the cognitive disorganization dimension, also have GFP amplitude reductions 200 ms after target onset compared to participants with low schizotypal traits. Quantitatively, the difference between high and low scoring participants is much smaller than between patients and controls. Nonetheless, the result shows that deficits are qualitatively similar along the schizophrenia continuum even in a non-clinical population. Third, patients with 22q11 deletions syndrome, who also suffer from psychosis in 30% of the cases, do not show masking deficits. Deficits were expected but potentially because of high co-morbidity with other disorders, I did not find the same neural signature. Fourth, patients with major depressive disorder are not impaired in the ST, however, their neural correlates are lower compared to controls, though not as low as schizophrenia patients. This is surprising given the good behavioral performance. Despite the GFP reduction, the neural signature of depressive patients differs from the one of schizophrenia patients. They do not show the amplitude increment as a function of task difficulty seen in controls, siblings of patients with schizophrenia, and patients with schizophrenia. Finally, I describe preliminary results from on-going studies on healthy aging, autism and bipolarity. The objective is to make all populations fit in a unified framework.