Role of ADAMTS2 metalloprotease in schizophrenia
Schizophrenia affects 1% of the world’s population, resulting in a high personal, social and economic cost (Crespo-Facorro in press).
In recent years, our group has described a set of over-expressed genes associated with the disease whose expression reverts to normal after three months of treatment, which are also associated with clinical improvement. ADAMTS2 is the most over-expressed gene in independent patient samples, and is moderated by antipsychotic action in respondent patients (Ruso-Julve et al, 2019). This line of research creates a translational bridge between clinical and basic research that will allow the following objectives to be met:
- Generate transgenic mouse model over-expressing ADAMTS2 and investigate the influence of ADAMTS2 on the occurrence of schizophrenia.
- Study the interaction between ADAMTS2 and reelin.
- Test the basic findings in samples of respondent and non-respondent to antipsychotic treatment patients.
- To demonstrate the improvement in diagnosis and response prediction of the identified markers in new cohorts of patients.
– Crespo-Facorro B et al. (en prensa) ‘Head-To-Head Aripiprazole and risperidone comparison in the treatment of first-episode nonaffective psychosis: a 12-week randomized, flexible-dose, open-label trial’.
– Ruso-Julve, F. et al. (2019) ‘Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics’, Translational psychiatry. Nature Publishing Group UK, 9(1), p. 306.