Blood biomarker discovery in drug-free schizophrenia: the contribution of proteomics and multiplex immunoassays

Abstract

Recent evidence supports an association between systemic abnormalities and the pathology of psychotic disorders which has led to the search for peripheral blood-based biomarkers. Areas covered: Here, we summarize blood biomarker findings in schizophrenia from the literature identified by two methods currently driving biomarker discovery in the human proteome; mass spectrometry and multiplex immunoassay. From a total of 14 studies in the serum or plasma of drug-free schizophrenia patients; 47 proteins were found to be significantly altered twice or more, in the same direction. Pathway analysis was performed on these proteins, and the resulting pathways discussed in relation to schizophrenia pathology. Future directions are also discussed, with particular emphasis on the potential for high-throughput validation techniques such as data-independent analysis for confirmation of biomarker candidates. Expert commentary: We present promising findings that point to a convergence of pathophysiological mechanisms in schizophrenia that involve the acute-phase response, glucocorticoid receptor signalling, coagulation, and lipid and glucose metabolism.

Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress

“…Blood-based studies of the ARMS and UHR, focusing on inflammation markers, have been undertaken and have shown largely consistent changes implicating a proinflammatory process in both psychosis and affective disorder [8,9]. These findings are supported and extended by discovery proteomic studies of first episode psychosis and schizophrenia implicating the acute-phase response, glucocorticoid receptor signalling, coagulation, and lipid and glucose metabolism [10,11]. Furthermore, inflammatory cytokines, chemokines, and growth factors have been assessed in the blood during the perinatal periods and during childhood in subjects who subsequently developed schizophrenia, and in those with a first episode psychosis [12][13][14][15][16].…”

“…Overall, the complement and coagulation cascade has previously been identified as the most significant pathway implicated in plasma samples of drug naive schizophrenia patients [10,28,41,[55][56][57][58][59]. The cause of these changes are not known, but are in keeping with evidence for raised inflammatory tone preceding psychosis and major psychiatric disorders generally [8,[12][13][14][15][16][17]60].…”

Recognition-behavioral stress-coping humoral glycolipids produced by medicated major psychoses patients

“…Some researchers have investigated biomarkers of schizophrenia in the view of the proteins, the metabolites and the RNAs in the peripheral blood [25,26]. Mechanism of S2-3G produced in the peripheral blood is not be clarified in the present time, however, I understand the humoral glycolipid would be considered as another biomarker identifying schizophrenia.…”

Circulating biomarkers in schizophrenia: a proteomics perspective

“…Due to the multifactorial picture of schizophrenia, possibly one type of approach is not sufficient to discover one specific biomarker. A combination of imagining techniques, neuropsychology, electroencephalograms (EEGs) and proteomic approaches should be interesting and challenging to identify a multifactorial signature of the disease [95]. Additionally, such a combined approach may help to overcome present difficulties in biomarker discovery such as the issue of antibody availability and lack of comprehensive proteome coverage [95].…”

“…First-onset drug-naive schizophrenia individuals are the preferred subjects of study and their recruitment has a low rate, leading to longer project duration and consequently longer storage times and higher variability [94,95]. On the other hand the recruitment of chronically ill medicated patients is easier but comes with the disadvantage of making it necessary to clearly distinguish drug from disease-related changes, which is not as straightforward as it may seem; it is a factor that is many times disregarded in previous studies, explaining to some extent the low reproducibility of the findings [96].…”