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REVIEW ARTICLE Serum Markers Related to Depression: a Systematic Review R Journal of Medical and Biomedical Sciences (2017) 6(3): 30- 42 © UDS Publishers Limited All Right Reserved 2026-6294 doi: http://dx.doi.org/10.4314/jmbs.v6i3.5 REVIEW ARTICLE Serum markers related to depression: A systematic review R. Tavakoli1, A. Nouri2, R. Masoudi3 , M. Mirhoseini4 and F. Ahmadpour5 1,5Department of Biochemistry, School of Medicine, Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, 2Student Research Committee, 3Community Oriented Nursing Midwifery Research Center, Shahrekord University of Medical Sciences, Shahrekord, 4Shiraz University of Medical Science, Shiraz, Iran. Depression has a multifactorial aetiology and is one of the most common neurological and psychiatric disor- ders that are associated with imbalance in certain inhibitory and excitatory neurotransmitters and impair- ment of the brain-derived neurotrophic factor (BDNF). This review study was conducted to investigate the effect of BDNF and neuromediators on the development and severity of depression. To conduct this sys- tematic review, relevant publications that were published between 2000 and 2016 and were indexed in the PubMed, Google Scholar, Scopus and Web of Science databases were retrieved using the depression, serum markers, neurotransmitters, serotonin, BDNF, dopamine, glutamate and gamma amino-butyric acid search terms. A total of 89 articles were included in final analysis. Depression is associated with imbalance of certain neurotransmitters such as serotonin, dopamine, norepinephrine, melatonin and glutamate in the central nervous system and impairment of BDNF. Taken together, there is a significant relationship between depression and neurome- diators, and the decrease and increase in these mediators plays a significant role in depression. Studies have also confirmed that the antidepressant effect of drugs and medicinal plants is essentially related to the sero- tonergic pathway, especially the 5-HT1A receptor, and drugs and medicinal herbs are likely to exert their antidepressant activity through altering dopaminergic and serotonergic systems. Journal of Medical and Biomedical Sciences (2017) 6(3), 30 - 42 Keywords: Depression, Serum markers, Neuromodulator, Brain-derived neurotrophic factor INTRODUCTION been introduced to express and control anxiety, Depression is a chronic disabling disease that affects depression and psychological behaviors, one of one in six people in the United States (Kessler et al., which is the limbic system, which regulates neu- 2005). According to the World Health Organization ronal activity by genomic or non-genomic mecha- (WHO)'s report, about 350 million people world- nisms through regulation of enzymes, neural media- wide are suffering from depression, and by 2020, it tors, etc (Khayeri et al., 2016). will be the second leading disease, after cardiovascu- lar diseases, in the world (Kessler et al., 2003). However, depression has a multifactorial aetiology (including biological, genetic, psychological and Depression is the main cause of the incidence of 50- environmental factors), which is associated with the 70% of suicides (Lecomte and Fornes, 1998). De- imbalance in different neurotransmitters (inhibitory pression has certain symptoms such as loss of energy and excitatory), as well as impairment of the brain and motivation, feeling guilty, difficulty maintaining neurotrophic factor (BDNF) in most cases (Maletic concentration, feeling depressed, sleep disorders, et al., 2007; Maes et al., 2011; Lopresti et al., 2013; change in appetite, disappointment, thoughts of Mazaheri et al., 2014; Rabiei et al., 2014) so that it death and suicide (Eslami et al., 2016; Etemadifar et can be argued that depression is associated with a al., 2017). Different neuroanatomical regions have decrease in the transmission of functional amine- dependent neurotransmitters in the synapse and an increase in monoamines and glutamate in the syn- Correspondence: Reza Masoudi, Shahrekord University aptic cleft, which is the basis of the amine hypothe- of Medical Sciences, Rahmatiyeh, Shahrekord, Iran. sis of depression (Berk et al., 2013). Email: [email protected]. Besides that, depression is associated with a de- 30 A review on serum markers related to depression Tavakoli et al., crease in the plasma concentrations of important causes depression and, in more severe cases, Alz- antioxidants such as vitamin E and coenzyme Q, as heimer's and cardiovascular disease (Sauer et al., well as the reduction of the activity of oxidative en- 2003; Salmon, 2007). zymes, such as glutamine peroxidase. Other studies have shown that the cysteine at the 704 (Cys704) is Under stressful conditions, with a low serotonin associated with depressive disorders, decrease in the level, there is a significant increase in the immune volume of hippocampal substantia nigra and reduc- system proteins that play an important role in Alz- tion of anisotropy of the fragments in the prefrontal heimer's and cardiovascular disease. That's why white matter (Smagin et al., 2001; Callicott et al., most depressed and hostile people whose levels of 2005; Watson and Mackin, 2009). This review was serotonin are low are affected by heart disease, Alz- conducted with the aim of investigating neurotrans- heimer's disease, and other illnesses that increase mitters levels in different brain regions and the effect the response to the immune system. In this way, the of neurotransmitters and BDNF on development use of serotonin-enhancing drugs for depression and severity of depression. can also reduce the risk of heart disease and Alzhei- mer's (Sauer et al., 2001; Eliecer et al., 2003). Seroto- To conduct this systematic review, relevant publica- nin also has an inhibitory effect on the function of tions that were published between 2000 and 2016 the N-methyl-D-aspartate (NMDA) receptor and were indexed in the PubMed, Google Scholar, Scopus through centrally releasing ascorbic acid, and can and Web of Science databases were retrieved using the thus reduce anxiety and depression (BJ; Diplama depression, serum markers, neurotransmitters, serotonin, JR). BDNF, dopamine, glutamate and gamma amino-butyric acid search terms. A total of 89 articles were included BDNF in final analysis. BDNF is another factor involved in depression. BDNF in humans is coded by the BDNF gene lo- Different neuromediators and their association cated on chromosome 11(Maisonpierre et al., 1991; with depression Binder and Scharfman, 2004). BDNF, a member of Serotonin the neurotrophin family, is one of the neuronal Serotonin is one of these neuromediators. Serotonin growth-associated factors that are commonly ex- acts on the functioning of the central nervous sys- pressed in the brain and surrounding tissues. tem (CNS) and cardiovascular, renal, immune and BDNF acts in certain neurons of the central and gastrointestinal systems; any disorder in the synthe- peripheral nervous system for survival, growth, and sis, metabolism and reuptake of serotonin leads to differentiation of neurons and formation of new symptoms and diseases such as schizophrenia, de- synapses(Acheson et al., 1995; Huang and Reich- pression, obsessive-compulsive disorder (OCD) and ardt, 2001). learning disability (Amiri et al., 2016; Solati et al., 2017a). Serotonin also affects many physiological BDNF is active in areas of the brain that are in- activities, including mechanisms of anxious, appetite, volved in learning, memory and thinking, such as sexual behavior, sleep-wake cycle and peristal- the hippocampus, cortex and anterior cranial fossa sis (Oláh et al., 2005). Decreased serotonin levels in (Yamada and Nabeshima, 2003). BDNF is also ex- the brain of Alzheimer's patients can lead to numb- pressed in the retina, motor neurons, kidneys, saliva ness, learning disabilities and aging(Kalbitzer, 2009). and prostate (Mandel et al., 2009) . This factor trig- gers intracellular cascades, and ultimately produces Many antidepressants work to increase serotonin and differentiates new neurons by binding to cer- levels in synapses, including selective serotonin tain tyrosine kinase receptors. The neurotrophic reuptake inhibitors (SSRIs) that increase serotonin depression hypothesis states that depression is re- concentrations in the CNS. It can therefore be ar- lated to the reduction of BDNF and its treatment gued that the reduction of serotonin in the brain reduces depressive behaviors and increases BDNF 31 A review on serum markers related to depression Tavakoli et al., levels(Duman, 2002). Clinical trials have shown that (Shirayama and Chaki, 2006). serum BDNF levels are significantly higher in de- Glutamate pressed people than in healthy people (Karege et al., Glutamate is another neuromediator. Glutamate is 2002; Karege et al., 2005). a excitatory neurotransmitter in the chemical syn- apse of the vertebrate nervous system. Glutamate is Dopamine a neuromediator that generates various cellular cas- Dopamine is another neuromediator involved in cades in chemical synapses. Glutamate is also one depression, which is expressed in the areas of the of the main neurotransmitters in the CNS, which brain that regulate movements, feelings and emo- stimulates the neurons, creating potential for action. tions. Dopamine, as a stabilizing agent of the brain, This neurotransmitter is involved in the develop- plays a very important role in regulating the flow of ment of behavioral diseases, such as depression, information from the brain to other parts of the through its receptors, which include two groups, body (Solati et al.,
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