Translational approach to the identification of neurobiological markers in the early phase of psychosis

Early detection of psychotic disorders has become an essential focus for research, leading to the emergence of a preventive approach. There is an important need for basic neurobiological research in this domain. We have therefore developed a translational research program based on three axes :

1. Cross sectional multimodal assessment of patients (clinical and neurobiological assessment, brain imaging, EEG) in the various stages of the disorder (prodromal phase, first episode, early relapse and chronic phase);
2. Longitudinal multimodal assessment of patients through the successive stages of the illness starting from the prodromal phase, and
3. Bi-directional translation between human and animal models with experiments leading to similar endpoint assessments being conducted in both.
      

We test the hypothesis that redox imbalance and oxidative stress represent one core pathophysiological mechanism, resulting from the convergence of various causal genetic and environmental risk factors during neurodevelopment and leading to structural and functional connectivity impairments.

We are following main

(a) To identify and validate stage specific biomarker profiles in order to allow early detection and monitoring of the efficacy of new drugs, both in animal models and humans;

(b) To identify potential new treatments and preventive targets based on new critical pathophysiological molecular signaling pathways.

In order to do so, biological correlates have been assessed with non-invasive technologies including :

• Blood and fibroblasts genetics, transcriptomics (collaboration with Dr Jean-Luc Martin), proteomics (collaboration with Dr Beat Riederer), epigenetics (collaboration with Dr Jean-René Cardinaux) and metabolomics, both in humans and animal models
• Electroencephalography (EEG) – Collaboration with Prof. Micah Murray, Center for Biomedical Imaging (EEG-CIBM)
• Magnetic Resonance Spectroscopy (MRS) – Collaboration with Prof. Rolf Gruetter, Center for Biomedical Imaging (CIBM)
• Magnetic Resonance Imaging (MRI), Diffusion Tension Imaging (DTI) and connectomics – Collaboration with Prof. Patric Hagmann, Service of Radiology (CHUV) and with Prof. Jean-Philippe Thiran, Signal Processing Laboratory 5 (LTS5, EPFL)

This research is conducted in collaboration between the Section Minkowski, TIPP program (Service of General Psychiatry, Prof. Philippe Conus and Dr Alessandra Solida) and the Unit for Research in Schizophrenia (Center for Psychiatric Neuroscience, Prof. Kim Do).

Our research program is financed by :

• Department of Psychiatry, CHUV
• Swiss National Science Foundation for National Center of Competence in Research “SYNAPSY” 51AU40_125759
• Swiss National Science Foundation – Grants # 310030-135736; 320030-130090; 320030-122419
• Fondation Alamaya
• Avina Stiftung
• Fondation Damm-Etienne