Background: Schizophrenia is a multifaceted neuropsychiatric disorder which almost certainly presents a heterogeneous group of aetiologies. A better molecular understanding of the disease onset and progression is urgently needed. Proteomics profiling approaches can be employed to investigate large numbers of patient and control samples in a single experiment. These large scale experiments are required to identify disease intrinsic molecular signatures as well as patient subgroups.
Methods: Multiple independent cohorts of first-onset, recent-onset, prodromal and pre-disease onset serum samples from patients with schizophrenia or prone to develop the disorder were investigated initially using a multiplexed ELISA approach; a subset of these samples were then investigated using a multiplexed SRM panel to identify significantly changing proteins.
Results: We have identified a number of highly significant peptides and proteins in serum that distinguish first-onset paranoid schizophrenia patients from healthy controls. Our findings suggest alterations in glucoregulatory, inflammatory and hormonal processes in drug-naïve patients with first-onset schizophrenia. Interestingly, we also identified disease-relevant metabolic and inflammatory changes in affected and unaffected siblings of schizophrenia patients and have preliminary evidence for the existence of schizophrenia sub-groups, based on the expression of serum proteins.
We also present preliminary results from a SRM study on dried blood spots (DBS’s) of newborn babies who later in life developed schizophrenia.
Conclusion: We have identified a robust biomarker panel for the diagnosis and prediction of schizophrenia using multiplexed ELISA and SRM techniques. Future applications of diagnostic or prognostic blood tests could aid clinicians in identification of vulnerable patients early in the disease process, possibly even prior to overt disease onset, allowing more effective therapeutic intervention and prevention.
Thank you to the Stanley Medical Research Institute for Centre support.
