Coding and Noncoding Gene Expression Biomarkers in Mood Disorders and Schizophrenia

Abstract

Mood disorders and schizophrenia are common and complex disorders with consistent evidence of genetic and environmental influences on predisposition. It is generally believed that the consequences of disease, gene expression, and allelic heterogeneity may be partly the explanation for the variability observed in treatment response. Correspondingly, while effective treatments are available for some patients, approximately half of the patients fail to respond to current neuropsychiatric treatments. A number of peripheral gene expression studies have been conducted to understand these brain-based disorders and mechanisms of treatment response with the aim of identifying suitable biomarkers and perhaps subgroups of patients based upon molecular fingerprint. In this review, we summarize the results from blood-derived gene expression studies implemented with the aim of discovering biomarkers for treatment response and classification of disorders. We include data from a biomarker study conducted in first-episode subjects with schizophrenia, where the results provide insight into possible individual biological differences that predict antipsychotic response. It is concluded that, while peripheral studies of expression are generating valuable results in pathways involving immune regulation and response, larger studies are required which hopefully will lead to robust biomarkers for treatment response and perhaps underlying variations relevant to these complex disorders.

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

“…However, such tissue presents many limitations including access and collection of large sample sizes, tissue preparation and conservation, and antemortem diagnosis. With the aim of developing biomarkers, blood samples have been increasingly utilized because they are easily obtained and allow longitudinal follow-up of gene expression some of which is also correlated in brain tissue (Mamdani et al, 2013;Woelk et al, 2011).…”

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

“…Secondly, several cotranscriptional and posttranscriptional processes are involved for transforming mRNAs into functional proteins and the relationship between the level of expression of a given mRNA and the activity of the encoded protein is not always straightforward. On the one hand, to be defined as a biomarker, a link between measurement, pathophysiology or biological effect is not mandatory [44,45]. On the other hand, it would be interesting to know if variations of SLC6A4 gene expression can be correlated with potential biological mechanisms, in particular, if gene expression variation is associated with a change in protein expression and biological function of 5HTT.…”

Differential Gene Expression in Age-Related Macular Degeneration

“…lincRNAs can interact with DNA, other RNAs, and/or proteins; furthermore, they may control transcriptional silencing via epigenetic regulation and chromatin remodeling. For example, in body fluids such as serum from patients with neuropsychiatric disorders, ncRNAs show altered expression when compared with controls, and therefore may be used as biomarkers to predict disease development (Mamdani et al 2013). Similarly, for onset and progression of diseases such as AMD, miRNAs are proposed to be useful biomarkers (Hrdlickova et al 2014) as they may be specific to body fluids.…”