A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

Abstract

Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets.

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

“…In the present study, we conducted two meta-analyses in blood and brain using the raw data of 15 microarray studies to investigate gene expression from nearly 1000 subjects, equally divided between SCZ patients and nonpsychiatric controls. To our knowledge, no meta-analysis has been previously conducted on blood microarray data from SCZ, although several studies had combined data from two to seven human postmortem brain tissue microarray studies (Hagihara et al, 2014;Logotheti et al, 2013;Mistry et al, 2013a,b;Perez-Santiago et al, 2012;Torkamani et al, 2010). Gene expression network analyses, which describe the interactions among groups of transcripts, demonstrated well-preserved membership and connectivity of case modules relative to control modules (Chen et al, 2013;Torkamani et al, 2010).…”

“…Although SCZ has been viewed, mainly through imaging studies, as a disorder of reduced functional and structural cortical connectivity, it is proposed that this is not driven by differences in underlying molecular connectivities but rather from altered expression levels of genes with roles in important biological processes. The search for biological processes that are altered in SCZ has consistently revealed those involved in neuron development (Chen et al, 2013;Torkamani et al, 2010), metallothioneins (Chen et al, 2013;Logotheti et al, 2013;Perez-Santiago et al, 2012), energy metabolism (Hagihara et al, 2014;Mistry et al, 2013a,b;Torkamani et al, 2010), ubiquitination (Mistry et al, 2013a,b), and defense/immune/inflammatory response (Logotheti et al, 2013;Mistry et al, 2013a,b). Importantly, the 264 genes that were dysregulated in our brain meta-analysis (q-value b 1.0E−4) confirmed the involvement of the last four biological processes that were also enriched in other microarray studies (Altar et al, 2005;Arion et al, 2007;Iwamoto et al, 2005;Saetre et al, 2007;Schmitt et al, 2011) (see Materials and Table 4 Gene ontology analysis of dysregulated genes in blood meta-analysis (q ≤ 0.01).…”

Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters

“…Thus, the differential regulation observed in the present study is in agreement with earlier observations. Alterations in LAT functionality have been implicated in many neuronal disorders, including attention-deficit hyperactivity disorder, bipolar disorders and schizophrenia (Johansson et al, 2011;Logotheti et al, 2013). In addition, sex hormones are important for the development, modulation and protection of neuronal functions and have been implicated in the pathophysiology of mental diseases such as schizophrenia (Markham, 2012;Moore et al, 2013).…”

Gene Expression Analysis of Fibroblasts from Patients with Bipolar Disorder

“…This enzyme is responsible for the active transport of sodium and potassium through the cell membrane. Additionally, active amino acid transport systems may be subsequently influenced concluding to deregulation of the active transport of amino acids, implicated in BD [57].…”