Magdalena Budisteanu1, Sorina Mihaela Papuc1, Dan Riga2¸ Sorin Riga2, Aurora Arghir1
1Victor Babes National Institute of Pathology, 2Prof Alexandru Obregia Clinical Hospital of Psychiatry
Keywords: schizophrenia; synaptic dysfunction; molecular genetics

Schizophrenia (SZ) is a severe mental illness characterized by a wide range of defective cognitive function and a complex set of symptoms. SZ represents one of the major challenges for society, with large unmet patient needs and substantial health care costs. Various studies on the genetic risk architecture and aberrant brain functional connectome of SZ have implicated synaptic dysfunction in the pathophysiology, yet the precise mechanisms remain elusive.
We present the aim and scientific objectives of an ERA-NET NEURON (SYNSCHIZ) project, started in May 2018.
The main aims of SYNSCHIZ are to uncover the genetic architecture that increases the risk for synaptic dysfunction in SZ using large international cohorts; to integrate the identified genes into the development of novel computational models of synapse dysfunction; to experimentally validate these models in neuronal cell cultures derived from stem cells; and to link gene- and neuron-level discoveries to brain network level in SZ patients focusing on the SZ prodrome and in individuals at ultra-high risk for psychosis in a clinical setting.
Obregia Clinical Hospital of Psychiatry is partner in a consortium of 6 institutions coordinated by the Norwegian Centre for Mental Disorders Research, Oslo. The Romanian partner has already implemented a comprehensive diagnostic approach consisting of a standardized set of clinical tools for deep neuro-psychiatric phenotyping, high resolution bioimaging (3T brain MRI), and biochemical investigations. The genomewide genotyping of the cohort and subsequent functional studies will be performed at other consortium partner sites.
SYNSCHIZ implements a strong translational component that will transfer scientific discoveries into clinical application. By identifying biomarkers useful for early detection and prognostic predictions, and by gaining a deep insight into SZ neurobiology, the project aims to improve the treatment and care of SZ patients.