epidermal-growth-factor and Depressive-Disorder--Major

Major depression and anxiety are common psychiatric illnesses whose etiology remains incompletely understood. This review highlights progress in understanding the etiology of these illnesses through genetic strategies and looks forward to their impact on geriatric psychiatry. We briefly address three broad domains of progress, namely 1) genetic approaches to etiology, including linkage and association studies, pharmacogenetics ("personalized medicine"), and gene x environment interactions; 2) mechanisms of thyroid and testosterone action via nuclear receptors, given these hormones' status as possible augmenters of antidepressants; and 3) the role of the neuroimmune system as a contributor to the stress response. Genetic strategies offer one path for converting correlational findings into causal pathways while complementing studies of a gene's function at the molecular, cellular, network, and whole-organismal levels. Neuroendocrine supplementation (thyroid and testosterone) has a long history and tradition. A molecular understanding of nuclear receptor pathways and their coactivators, the mediator complex proteins, provides a rationale for improved targeting of hormonal action in a tissue-selective manner, yielding drugs with improved safety and efficacy. Neural-immune interactions in psychiatric illness remain tantalizing topics. Research suggests that cytokine pathways may contribute to the maintenance or susceptibility to stress, anxiety, and depressive disorders. The reciprocal and recursive interactions among basic science, drug discovery, and clinical science will continue to provide hopeful themes for improving the lives of patients with treatment-refractive psychiatric illness.

Topics: Aged; Anxiety; Depressive Disorder, Major; Epidermal Growth Factor; Forecasting; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Geriatric Psychiatry; Humans; Nerve Net; Serotonin Plasma Membrane Transport Proteins; Testosterone; Thyroid Gland; United States

Major depressive disorder (MDD) is a heterogeneous mental disorder having a very diverse course and causing a significant changes in daily life. Though the exact pathophysiology of depression is still not known, an alteration in the serum levels of cytokines and neurotrophic factors was seen in MDD subjects. In this study, we compared the serum levels of 'pro-inflammatory cytokine leptin and neurotrophic factor EGF' in healthy controls (HCs) and MDD patients. To make the findings more accurate, we eventually looked for a correlation between altered serum leptin and EGF levels and the severity of the disease condition.. For this case-control study, about 205 MDD patients were enrolled from the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, Dhaka, and about 195 HCs were enrolled from various parts of Dhaka. The DSM-5 was utilized to evaluate and diagnose the participants. The HAM-D 17 scale was used to measure the severity of depression. After collecting blood samples, they were centrifuged to produce clear serum samples. These serum samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits to measure serum leptin and EGF levels.. We observed lowered serum EGF levels in MDD patients compared to HCs (524.70 ± 27.25 pg/ml vs. 672.52 ± 49.64 pg/ml, p = 0.009), and HAM-D score was elevated in MDD patients compared to HCs (17.17 ± 0.56 vs. 2.49 ± 0.43, p<0.001). But no correlation was established between serum EGF levels and the severity of depression. However, no significant differences were observed between MDD patients and HCs in the case of serum leptin levels (p = 0.231).. Our study findings suggest that reduced serum EGF levels have an impact on the pathogenesis of depression. But as per our investigation, the severity of depression is not correlated with altered EGF levels. Our findings regarding the association of EGF with MDD would help to use EGF as a risk indicator of depression. We suggest further clinical investigations to determine the precise function of leptin and EGF in depression.

Topics: Bangladesh; Case-Control Studies; Cytokines; Depressive Disorder, Major; Epidermal Growth Factor; Humans; Leptin

Cardiovascular adverse complications represent a risk factor for increased cardiovascular morbidity and mortality in patients with major depressive disorder (MDD). However, there is little knowledge of adolescent MDD. We aimed to study complex cardiovascular autonomic regulation and early atherosclerotic damage with a focus on an analysis of heart rate variability (HRV), blood pressure variability (BPV), systolic time intervals, and measures of early atherosclerotic changes in adolescent MDD. Ninety depressive adolescents (34 boys, age 15.8 ± 1.3 yrs.) and 90 age-/gender-matched controls were examined. Evaluated parameters: HRV - time and spectral parameters, BPV - mean, systolic, and diastolic blood pressure, spectral systolic parameters; haemodynamic indices - stroke volume, cardiac output, total peripheral resistance, systolic time intervals - left ventricular ejection time, pre-ejection period; atherosclerotic indices - ankle-brachial index (ABI), pulse wave velocity, brachial-ankle pulse wave velocity, cardio-ankle vascular index; growth factors - epidermal growth factor (EGF), vascular endothelial growth factor associated with monocyte chemoattractant protein-1. Our results showed that the MDD group had significantly reduced HRV and higher BPV measures, shortened systolic time intervals, lower ABI, and higher EGF compared to controls. Concluding, our study revealed that adolescent MDD is associated with cardiovascular dysregulation and early vasculature dysfunction as preclinical markers of higher risk for cardiovascular morbidity, thus adolescence seems to represent an important age period for early diagnosis and prevention of later MDD-linked cardiovascular diseases manifesting in adulthood.

Topics: Adolescent; Adult; Ankle Brachial Index; Blood Pressure; Cardiovascular Diseases; Chemokine CCL2; Depressive Disorder, Major; Epidermal Growth Factor; Heart Rate; Humans; Male; Pulse Wave Analysis; Vascular Endothelial Growth Factor A

Epidermal growth factor (EGF) and Fibroblast Growth Factor-2 (FGF-2) are growth factors involved neuronal growth and synaptic plasticity. These markers have been implicated in neuropsychiatric disorders, including major depression. However, no particular studies of EGF and FGF-2 have been conducted in older adults with major depressive disorder (MDD). In this study, we aim to investigate the plasma levels of EGF and FGF-2 in elderly with MDD. We included 89 older adults with MDD and 51 older (healthy control, HC) adults. The cognitive performance was evaluated by the Mattis Dementia Rating Scale (MDRS). The EGF and FGF-2 were measured by using multiplex assay for LUMINEX platform. There were also no significant differences between the patient group in terms of plasma levels of EGF and FGF-2 when compared to the HC group. There were not any significant correlations between plasma levels of EGF or FGF2 and MDRS total or individual scores in patient group and HC. There were significant correlations between plasma levels of EGF and FGF2 in both patient group and HC. Further study on plasma levels of EGF and FGF2 should be implemented in larger samples in elderly with MDD.

Topics: Aged; Biomarkers; Case-Control Studies; Depressive Disorder, Major; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Humans; Male

The current diagnostic tests for mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), have limitations. Inflammatory markers, growth factors, and oxidative stress markers are involved in the pathophysiology of mood disorders. A multi-assay biological diagnostic test combining these biomarkers might improve diagnostic efficiency. The plasma levels of soluble tumor necrosis factor receptor 2 (sTNFR2), epidermal growth factor (EGF), and myeloperoxidase were measured in 40 MDD patients, 40 BD patients and 40 controls in a Japanese population. We also investigated the plasma levels of these markers in 40 patients with schizophrenia to determine the utility of these markers in differential diagnosis. The plasma levels of sTNFR2 were significantly higher in BD and schizophrenia patients than in controls. The plasma levels of EGF and myeloperoxidase were significantly higher in patients with BD than in controls. The correct classification rate obtained from discriminant analysis with sTNFR2 and EGF between controls and mood disorders was 69.2%, with a sensitivity and specificity of 62.5% and 82.5%, respectively. The correct classification rate obtained from discriminant analysis with sTNFR2 and EGF between controls and BD was 85.0%, with a sensitivity and specificity of 77.6% and 92.5%, respectively. Our results suggest that sTNFR2 and EGF could be biological markers of BD. Further studies are needed to determine the utility of these markers in diagnostic tests for mood disorders.

Topics: Aged; Biomarkers; Bipolar Disorder; Case-Control Studies; Depressive Disorder, Major; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Mood Disorders; Peroxidase; Receptors, Tumor Necrosis Factor, Type II; Schizophrenia

Major depressive disorder (MDD) is a main public health concern worldwide. Despite extensive investigations, the exact mechanisms responsible for MDD have not been identified. Epidermal growth factor (EGF) and insulin growth factor binding protein-3 (IGFBP-3) are involved in brain function. Tumour suppressor protein p53 is widely involved in neuronal death in response to different forms of acute insults and neurological disorders. The present study focuses on the possible associations of the single-nucleotide polymorphisms (SNP) of. The present case-control association study was carried out in 111 confirmed MDD patients and 207 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods.. Logistic regression analysis showed no association between SNPs of selected genes and MDD risk in the Slovak population. However, the stratification of individuals by gender revealed that males carrying. Our results suggest the protective effect of minor allele 72C of

Topics: Adult; Aged; Aged, 80 and over; Alleles; Case-Control Studies; Depressive Disorder, Major; Epidermal Growth Factor; Female; Genes, p53; Genetic Predisposition to Disease; Genotype; Humans; Insulin-Like Growth Factor Binding Protein 3; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Slovakia

Despite decades of intensive research, the development of a diagnostic test for major depressive disorder (MDD) had proven to be a formidable and elusive task, with all individual marker-based approaches yielding insufficient sensitivity and specificity for clinical use. In the present work, we examined the diagnostic performance of a multi-assay, serum-based test in two independent samples of patients with MDD. Serum levels of nine biomarkers (alpha1 antitrypsin, apolipoprotein CIII, brain-derived neurotrophic factor, cortisol, epidermal growth factor, myeloperoxidase, prolactin, resistin and soluble tumor necrosis factor alpha receptor type II) in peripheral blood were measured in two samples of MDD patients, and one of the non-depressed control subjects. Biomarkers measured were agreed upon a priori, and were selected on the basis of previous exploratory analyses in separate patient/control samples. Individual assay values were combined mathematically to yield an MDDScore. A 'positive' test, (consistent with the presence of MDD) was defined as an MDDScore of 50 or greater. For the Pilot Study, 36 MDD patients were recruited along with 43 non-depressed subjects. In this sample, the test demonstrated a sensitivity and specificity of 91.7% and 81.3%, respectively, in differentiating between the two groups. The Replication Study involved 34 MDD subjects, and yielded nearly identical sensitivity and specificity (91.1% and 81%, respectively). The results of the present study suggest that this test can differentiate MDD subjects from non-depressed controls with adequate sensitivity and specificity. Further research is needed to confirm the performance of the test across various age and ethnic groups, and in different clinical settings.

Topics: Adult; alpha 1-Antitrypsin; Apolipoprotein C-III; Biomarkers; Case-Control Studies; Depressive Disorder, Major; Epidermal Growth Factor; Female; Humans; Hydrocortisone; Male; Peroxidase; Pilot Projects; Prolactin; Receptors, Tumor Necrosis Factor, Type II; Resistin; Sensitivity and Specificity

Electroconvulsive therapy (ECT) is mainly used to treat medication resistant major depressive disorder (MDD) patients, with a remission rate of up to 90%. However, little is known about the serum molecular changes induced by this treatment. Understanding the mechanisms of action of ECT at the molecular level could lead to identification of response markers and potential new drug targets for more effective antidepressant treatments. We have carried out a pilot study which analysed serum samples of MDD patients who received a series of ECT treatments over 4 weeks. Patients received only ECT treatments over the first two weeks and a combination of ECT and antidepressant drugs (AD) over the subsequent two weeks. Blood serum analyses were carried out using a combination of multiplex Human MAP® immunoassay and liquid-chromatography mass spectrometry (LC-MS(E)) profiling. This showed that ECT had a predominant acute effect on the levels of serum proteins and small molecules, with changes at the beginning of ECT treatment and after administration of the ECT+AD combination treatment. This suggested a positive interaction between the two types of treatment. Changed molecules included BDNF, CD40L, IL-8, IL-13, EGF, IGF-1, pancreatic polypeptide, SCF, sortilin-1 and others which have already been implicated in MDD pathophysiology. We conclude that ECT appears to exert mainly acute effects on serum molecules.

Topics: Adaptor Proteins, Vesicular Transport; Adult; Antidepressive Agents; Biomarkers; Brain-Derived Neurotrophic Factor; Chromatography, High Pressure Liquid; Combined Modality Therapy; Cytokines; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Electroconvulsive Therapy; Epidermal Growth Factor; Female; Humans; Immunoassay; Insulin-Like Growth Factor I; Male; Mass Spectrometry; Middle Aged; Pilot Projects; Proteomics; Reproducibility of Results

The precise mechanism of major depressive disorder (MDD) is poorly understood. On the basis of the neurotrophin hypothesis, initial findings from our previous studies, and the functions of epidermal growth factor (EGF) in the central nervous system, we proposed that EGF might contribute to the development of MDD, which was investigated in this study.. Eight single nucleotide polymorphisms (SNPs) within the EGF gene were genotyped in 463 patients with MDD and 413 control participants among a Chinese population; of these, the plasma EGF levels of 210 patients and 223 controls were determined using the enzyme-linked immunosorbent assay. To determine the effect of functional SNPs on EGF secretion in HEK293 cells, EGF levels in the supernatants of cultured cells were also assessed.. None of the informative SNPs showed an allelic association with MDD, but the cis-phase interaction between rs11569017 and rs11569126 was strongly associated with the illness (P=0.0027). The EGF levels in plasma were significantly lower in the patient group than in the control group (P<0.0001). The EGF levels were also significantly lower in patients with the rs11569017-TT genotype than those with either the AA genotype (P=0.013) or the AT genotype (P=0.004); the rs11569017 minor allele significantly affected the expression of the EGF gene (P=0.0004).. The cis-phase interaction between the SNPs within the EGF locus may contribute toward the etiology of MDD. The plasma EGF levels may be a useful biomarker for the early diagnosis, treatment, and prognosis of major psychiatric disorders.

Topics: Adult; Alleles; Depressive Disorder, Major; Epidermal Growth Factor; Female; Genetic Association Studies; Genetic Predisposition to Disease; HEK293 Cells; Humans; Male; Polymorphism, Single Nucleotide

To study the association between the epidermal growth factor (EGF) gene and intelligence in patients with major depression.. Intelligence measurement using Wechsler Adult Intelligence Scale (WAIS) was performed on 120 unrelated patients with major depression and 46 control subjects. Blood was collected from all subjects for extraction of genomic DNA. Four single nucleotide polymorphisms (SNPs) in the EGF gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI- TOF-MS).. Mean scores of both score lang and score task, two subtests in WAIS, differed significantly between major depression patients and controls (P<0.0001). Quantitative trait analysis showed that the genotype of rs2250724 was closely associated with score lang and score task in major depression patients. The associations were still significant after 10 000 permutations.. Although preliminary, our results provide evidence for association between the EGF gene and intelligence in patients with major depression. Genetic variation in the EGF gene may increase the susceptibility of major depression.

Topics: Adult; Case-Control Studies; Depressive Disorder, Major; Epidermal Growth Factor; Female; Humans; Intelligence; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization