epidermal-growth-factor and Bipolar-Disorder

Cellular migration is a ubiquitous feature that brings brain cells into appropriate spatial relationships over time; and it helps in the formation of a functional brain. We studied the migration patterns of induced pluripotent stem cell-derived neural precursor cells (NPCs) from individuals with familial bipolar disorder (BD) in comparison with healthy controls. The BD patients also had morphological brain abnormalities evident on magnetic resonance imaging. Time-lapse analysis of migrating cells was performed, through which we were able to identify several parameters that were abnormal in cellular migration, including the speed and directionality of NPCs. We also performed transcriptomic analysis to probe the mechanisms behind the aberrant cellular phenotype identified. Our analysis showed the downregulation of a network of genes, centering on EGF/ERBB proteins. The present findings indicate that collective, systemic dysregulation may produce the aberrant cellular phenotype, which could contribute to the functional and structural changes in the brain reported for bipolar disorder. This article has an associated First Person interview with the first author of the paper.

Topics: Bipolar Disorder; Brain; Epidermal Growth Factor; Humans; Magnetic Resonance Imaging; Neural Stem Cells

Epidermal growth factor (EGF) belongs to a family of growth factors implicated in the etiology of psychiatric illnesses. We conducted this cross-sectional case-control study to determine whether (1) serum EGF levels differ between bipolar disorder (BD) patients and non-BD comparison subjects, (2) EGF levels in patients are influenced by mood illness related factors (number of past mood episodes, medication treatment) and non-mood illness related factors (body mass index), and (3) lower EGF levels predict lower limbic brain volumes in BD.. We measured serum EGF in 51 early-stage BD patients and 22 healthy comparison subjects (HS). A subset of 25 patients underwent cerebral magnetic resonance imaging (MRI). Participants were assessed at the University of British Columbia Mood Disorders Centre between June 2004 and June 2012.. A general linear model with diagnosis and BMI category (overweight/obese vs normal weight) as factors showed that patients had lower mean log(e)-transformed EGF (LnEGF) than HS (4.99 vs 5.47, p = .011). There was no effect of BMI and no diagnosis x BMI interaction. Multiple linear regression models showed that in patients, more past mood episodes predicted lower LnEGF (β = -0.358, t = -2.585, p = .013) and lower LnEGF predicted lower bilateral temporal lobe volumes (left: β = 0.560, p = .011; right: β = 0.543, p = .009).. Our cross-sectional study design limits our ability to make inferences about the causal directions of the relationships between EGF, diagnosis, mood episodes, and brain volumes.. These findings provide preliminary evidence that EGF is a novel biomarker that may play a role in the pathophysiology of BD.

Topics: Bipolar Disorder; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Epidermal Growth Factor; Humans; Magnetic Resonance Imaging

Immune dysregulation plays a role in the vulnerability for mood disorders. Immune growth factors, such as Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein-2 (IGF-BP2), Epidermal Growth Factor (EGF), IL-7 and sCD25 have repeatedly been reported altered in patients with mood disorders. The aim of this study was to investigate levels of these factors in serum of adolescent bipolar offspring, who have a heightened risk for mood disorder development and to also analyze the data combined with previously published data. Growth factors were assessed by CBA/ELISA in adolescent bipolar offspring (n=96, mean age=16years) and in age- and gender-matched healthy controls (n=50). EGF belonged to a mutually correlating cluster of mainly neurotrophic compounds including S100B and BDNF, which were in general decreased in serum. IL-7, SCF, IGF-BP2 and sCD25, belonged to a different mutually correlating cluster of immune growth factors, which were in general increased: IGF-BP2 significantly in serum of offspring without a mood disorder, IL-7 and SCF in serum of offspring who had experienced a mood episode. This pattern of de- and increases was not different between bipolar offspring that developed or did not develop a mood disorder over time, apart from the IGF-BP2 level, which was near significantly higher in offspring later developing a mood disorder. Correlations with the previously published immune-cellular abnormalities were not found. In conclusion non-affected adolescents at familial mood disorder development risk were characterized by a distinct pattern of a series of compounds operating in a network of hematopoiesis, neurogenesis and inflammation.

Topics: Adolescent; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Child of Impaired Parents; Epidermal Growth Factor; Female; Humans; Inflammation; Insulin-Like Growth Factor Binding Protein 2; Intercellular Signaling Peptides and Proteins; Interleukin-7; Male; S100 Calcium Binding Protein beta Subunit; Stem Cell Factor

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