The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. These last 30 years, we witness an exponential rise in research on negative symptoms causes and treatments. The observed association of negative symptoms with impaired reward system function has stimulated research for the assessment of the potential sources of negative symptoms and for many different potential adjunctive treatments to ongoing antipsychotic medication. The main objective of this research thesis is to explore both the cause and the potential treatment candidate of negative symptoms.

The author explores sources of secondary negative symptoms (substance use), the prediction of the optimal dose of antipsychotics for acute exacerbation of schizophrenia, and the potential of different treatments for negative symptoms: prodopamingergic drugs, intra-nasal oxytocin, and physical exercise.

This work contributes to the progress made on the road to defining the most suitable evidence-based treatments for patients with negative symptoms. Overall, further research is clearly needed to develop specific treatments for negative symptoms.