Schizophrenia risk mutations lead to instable neuronal networks

Schizophrenie Systemmedizin

How does Schizophrenia work on the molecular level? In this study, dynamic network neuroscience techniques and neuroimaging methods were applied by scientists of the e:Med consortia IntegraMent to uncover the molecular and genetic contributions of glutamate and brain network dynamics.


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How does Schizophrenia work on the molecular level? What is the genetic impact on this disease? Up to now it was only known, that the interactions between brain regions follow different patterns and that the disease has a hereditable component. It was however not clear, which molecular and genetic implications
led to these changes. Studies show that lowered activity of the glutamate receptors and the thereby hindered signaling transfer between the neurons might be important.

e:Med scientists of the consortium IntegraMent with Urs Braun, Dr. Dr. Heike Tost and Professor Andreas Meyer-Lindenberg employed imaging processes and pharmacological interventions and hereby discovered that patients suffering from schizophrenia build neuronal networks with lower stability. This was traced back to an altered glutamatergic signaling transfer, which has a huge genetic impact. In this study the brain from patients and first degree relatives were examined via functional magnetic resonance tomography during performing a memory task (n-back test). It was already obvious here that the brain regions of patients communicate differently and build more labile networks compared to the control group.

Interestingly, dynamic networks of the patients’ relatives, which share half of the genetic risk gene load, show a similar type of aberrations. This altered network stability was intermediate between control persons and patients, which allows conclusions on a high genetic influence. In further experiments the control persons took a medication, which blocks the glutamate receptors. This induced limitation in signaling transfer led to a similar brain anomaly as previously observed within the patients. The scientists concluded that the glutamatergic receptors play a key role in building stable neuronal networks and thus in developing schizophrenia. Therefore, these neuronal dynamics are a prospective target for the development of efficient medication.


Original publication:

Braun, U., Schäfer, A., Bassett, D.S., Rausch, F., Schweiger, J.I., Bilek, E., Erk, S., Romanczuk-Seiferth, N., Grimm, O., Geiger, L.S., Haddad, L., Otto, K., Mohnke, S., Heinz, A., Zink, M., Walter, H., Schwarz, E., Meyer-Lindenberg, A., Tost, H., 2016. Dynamic brain network reconfiguration as a potential schizophrenia genetic risk mechanism modulated by NMDA receptor function. Proc. Natl. Acad. Sci. U.S.A. 113, 12568–12573.



Dr. Dr. Heike Tost, Urs Braun, Prof. Meyer-Lindenberg; Consortium IntegraMent
Central Institute of Mental Health, Mannheim