Schizophrenia is classified as a chronic mental disorder that exhibits many symptoms including hallucinations, delusions, impaired thoughts, behavior, and perceptions. The disorder itself is known to be associated with both genetic and environmental risk factors that play a role in affecting brain development. Adolescent-onset schizophrenia is severe with high morbidity and mortality and commonly goes hand in hand with treatment resistance. Why some patients present with schizophrenia during adolescence and others during adulthood is poorly understood. We aim to reveal the proteome of adolescent-onset patient-derived stem cells with adult-onset patient-derived stem cells, to find similarities and differences between adolescent-onset and adult-onset schizophrenia.
To answer this, we will assess olfactory neurosphere-derived cells, ‘ONS cells’, from adolescents and adults with schizophrenia and use a discovery-based proteomics approach using shotgun mass spectrometry. This will help to identify differentially expressed proteins in these two different cohorts of schizophrenia patients compared to healthy controls matched for both age and gender.
In our previous work, over 1000 proteins were identified, of which 241 proteins were found to be differentially expressed with a notable downregulation in both ribosomal and cytoskeletal proteins and protein synthesis pathways. To extend this work and to confirm our findings in independent samples, a new set of patients has been recruited and cells prepared.
After mass spectrometry, the data will be analyzed, differentially expressed proteins will be identified, and protein-protein interaction network searches will be conducted. Results will be compared and integrated with our previous findings.