Biological pathways modulated by antipsychotics in the blood plasma of schizophrenia patients and their association to a clinical response

Abstract

Proteomics is a valuable tool to unravel molecular mechanisms involved in human disorders. Considering the mediocre effectiveness of antipsychotics, which are the main class of drug used to treat schizophrenia, we analyzed a cohort of 58 schizophrenia patients who had blood collected before and after 6 weeks of antipsychotic treatment using a shotgun mass spectrometry proteomic profiling approach. Our aim was to unravel molecular pathways involved with an effective drug response. The results showed that all patients had essentially the same biochemical pathways triggered Independent of the antipsychotic response outcome. However, we observed that these pathways were regulated in different directions in blood samples from those who responded well to antipsychotics, compared with those who had a poorer outcome. These data are novel, timely and may help to guide new research efforts in the design of new treatments or medications for schizophrenia based on biologically relevant pathways.

Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients

“…The samples had already been obtained from a cohort comprised of 54 acute schizophrenia patients who were treated with either olanzapine ( n = 17), risperidone ( n = 23), or quetiapine ( n = 14) (Supplementary Table 1 ), as described previously ( 15 ). Diagnoses were performed using DSM-IV criteria and the Structured Clinical Interview (SCID-I) ( 17 ).…”

“…This is critical since different patients may show a better response to a distinct drug. In a recent publication, we reported on the analysis of plasma samples from a cohort of 58 schizophrenia patients using shotgun mass spectrometry proteomic profiling ( 15 ). Our objective was to identify proteins and protein pathways involved with an effective response to atypical antipsychotics, although, as with the above studies, no attempt was made to identify treatment-specific signatures.…”

Equivalent change enrichment analysis: assessing equivalent and inverse change in biological pathways between diverse experiments

“…Gil-Pisa, et al justified the use of their mouse model of schizophrenia based on its similarity in cytokine expression to a previously published model [10]. Martins-de-Souza, et al showed that responders showed the same pathways were affected, but in opposite directions, in poor vs. good responders to anti-psychotics [11]. Clearly, this idea has many potential applications.…”

Equivalent Change Enrichment Analysis: Assessing Equivalent and Inverse Change in Biological Pathways between Diverse Experiments

“…Gil-Pisa, et al justified the use of their mouse model of schizophrenia based on its similarity in cytokine expression to a previously published model (Gil-Pisa et al 2014). Martins-de-Souza, et al showed that responders showed the same pathways were affected, but in opposite directions, in poor vs. good responders to anti-psychotics (Martins-de-Souza et al 2015). Clearly, this idea has many potential applications.…”