GSK-3 parameters in lymphocytes of schizophrenic patients

BackgroundRecent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia patients.ObjectivesTo examine PBMC expression levels of AKT1 in schizophrenia patients versus controls, and to examine whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients.Methods/ResultsA case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N = 41) as compared to controls (N = 29). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR) = 0.05). Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool. We found significantly decreased PBMC expression of AKT1 (p<0.001, t = −4.25) in the patients. AKT1 expression was decreased in antipsychotic-free or -naive patients (N = 11), in florid psychotic (N = 20) and in remitted (N = 21) patients. A total of 1224 genes were differentially expressed between patients and controls (FDR = 0.05). Functional analysis of the entire deregulated gene set indicated deregulated canonical pathways involved in a large number of cellular processes: immune system, cell adhesion and neuronal guidance, neurotrophins and (neural) growth factors, oxidative stress and glucose metabolism, and apoptosis and cell-cycle regulation. Many of these processes are associated with AKT1.ConclusionsWe show significantly decreased PBMC gene expression of AKT1 in male, recent-onset schizophrenia patients. Our observations suggest that decreased PBMC AKT1 expression is a stable trait in recent onset, male schizophrenia patients. We identified several AKT related cellular processes which are potentially affected in these patients, a majority of which play a prominent role in current schizophrenia hypotheses.

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“…We did not find altered expression of the main downstream target of AKT, GSK-3, in concordance with previous reports [27], [28].…”

Section: Discussionsupporting

confidence: 93%

Marked Reduction of AKT1 Expression and Deregulation of AKT1-Associated Pathways in Peripheral Blood Mononuclear Cells of Schizophrenia Patients

et al. 2012

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“…Of these, SELENBP1 was identified as the strongest candidate biomarker among all genes differentially expressed in Sz, because it was the only gene showing significant differential expre ssion in a similar direction in both brain and blood [13] . However, the result of up-regulation of SELENBP1 [139] and up-regulation of GSK3A [112] in peripheral blood was not replicated in the other studies. Another study reported several genes related to nucleosome and histone structure were dysregulated in PBMC of both people with Sz and their siblings, suggesting a potential epigenetic mechanism underlying the risk state for the disorder [134] .…”

Section: The Human Transcriptome and Human Proteome Studiesmentioning

confidence: 71%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

137

108

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Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood World Journal of Psychiatry W J P oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

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“…GSK-3a protein and activity was shown to be decreased in a small number of cases relative to controls in this study. Two subsequent studies have examined GSK-3 activity in lymphocytes of patients with schizophrenia, one, using direct kinase assays, finding no difference [26] and the other, using immunoblotting, finding decreased Ser9 phosphorylation and, hence, increased activity [27]. Figure 2.…”

Section: Wnt Signal Alteration In Schizophreniamentioning

confidence: 99%