Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia.

Over the last decade, finding a reliable biomarker for the early detection of schizophrenia (Scz) has been a topic of interest. The main goal of the current review is to provide a comprehensive view of the brain, blood, cerebrospinal fluid (CSF), and serum biomarkers of Scz disease. Imaging studies have demonstrated that the volumes of the corpus callosum, thalamus, hippocampal formation, subiculum, parahippocampal gyrus, superior temporal gyrus, prefrontal and orbitofrontal cortices, and amygdala-hippocampal complex were reduced in patients diagnosed with Scz. It has been revealed that the levels of interleukin 1ß (IL-1ß), IL-6, IL-8, and TNF-α were increased in patients with Scz. Decreased mRNA levels of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), neurotrophin-3 (NT-3), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) genes have also been reported in Scz patients. Genes with known strong relationships with this disease include BDNF, catechol-O-methyltransferase (COMT), regulator of G-protein signaling 4 (RGS4), dystrobrevin-binding protein 1 (DTNBP1), neuregulin 1 (NRG1), Reelin (RELN), Selenium-binding protein 1 (SELENBP1), glutamic acid decarboxylase 67 (GAD 67), and disrupted in schizophrenia 1 (DISC1). The levels of dopamine, tyrosine hydroxylase (TH), serotonin or 5-hydroxytryptamine (5-HT) receptor 1A and B (5-HTR1A and 5-HTR1B), and 5-HT1B were significantly increased in Scz patients, while the levels of gamma-aminobutyric acid (GABA), 5-HT transporter (5-HTT), and 5-HT receptor 2A (5-HTR2A) were decreased. The increased levels of SELENBP1 and Glycogen synthase kinase 3 subunit α (GSK3α) genes in contrast with reduced levels of B-cell translocation gene 1 (BTG1), human leukocyte antigen DRB1 (HLA-DRB1), heterogeneous nuclear ribonucleoprotein A3 (HNRPA3), and serine/arginine-rich splicing factor 1 (SFRS1) genes have also been reported. This review covers various dysregulation of neurotransmitters and also highlights the strengths and weaknesses of studies attempting to identify candidate biomarkers.

Dysfunction in Brain-Derived Neurotrophic Factor Signaling Pathway and Susceptibility to Schizophrenia, Parkinson's and Alzheimer's Diseases.

Brain-Derived Neurotrophic Factor (BDNF) is a dominant neurotrophic factor in the brain which plays a crucial role in differentiation, regeneration and plasticity mechanisms. Binding of the BDNF to its high-affinity Tropomyosin-related kinase B (TrkB) receptor leads to phosphorylation of TrkB, thus activating the three important downstream intracellular signaling cascades within the neural cells including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Phospholipase C-γ (PLCγ), and mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathways. Transcription of these pathways is regulated by cAMP Response Element-Binding protein (CREB) transcription factor, which can upregulate gene expression. In this review, we attempted to explore the role of BDNF and its associated pathways in susceptibility to Schizophrenia (Scz), Alzheimer's (AD), and Parkinson's (PD) diseases. Furthermore, we discuss dysfunction in BDNF signaling pathway and the therapeutic potential of BDNF in the treatment of these disorders. The review covers various therapeutic strategies including BDNF gene therapy, transplantation of BDNFexpressing cell grafts, epigenetic manipulation, and intraparenchymal BDNF protein infusion as well. This review seeks to achieve these goals by reviewing recent studies on BDNF and examining the details of BDNF pathway in any of the above-mentioned diseases.