Neuroserpin in Bipolar Disorder

2020 ◽  
Vol 20 (7) ◽  
pp. 518-523
Author(s):  
Rugül Köse Çinar
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Polymerase Chain Reaction Method ◽  
Type I ◽  
Healthy Controls ◽  
Neuroprotective Effects ◽  
Expression Levels ◽  
Disease States ◽  
Cord Injury ◽  
System Functioning

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.

DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽  
2021 ◽  
Author(s):  
Beatriz Garcia-Ruiz ◽  
Manuel Castro de Moura ◽  
Gerard Muntané ◽  
Lourdes Martorell ◽  
Elena Bosch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bipolar Disorder ◽  
Mrna Expression ◽  
Gene Expression Analysis ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Genome Wide ◽  
Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

Lithium prevents grey matter atrophy in patients with bipolar disorder: an international multicenter study

2020 ◽  
pp. 1-10
Author(s):  
Franz Hozer ◽  
Samuel Sarrazin ◽  
Charles Laidi ◽  
Pauline Favre ◽  
Melissa Pauling ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Grey Matter ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Type I ◽  
Linear Regression Models ◽  
Neuroprotective Effects ◽  
History Of ◽  
International Multicenter Study ◽  
The Right

Abstract Background Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC). Methods We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse. Results Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li. Conclusions Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

Abnormal white matter integrity as a structural endophenotype for bipolar disorder

2016 ◽  
Vol 46 (7) ◽  
pp. 1547-1558 ◽  
Author(s):  
A. Sarıçiçek ◽  
N. Zorlu ◽  
N. Yalın ◽  
C. Hıdıroğlu ◽  
B. Çavuşoğlu ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
White Matter ◽  
Clinical State ◽  
Control Group ◽  
Type I ◽  
Healthy Controls ◽  
Corona Radiata ◽  
Left Posterior ◽  
Axis I ◽  
Bipolar Patients

BackgroundSeveral lines of evidence suggest that bipolar disorder (BD) is associated with white matter (WM) pathology. Investigation of unaffected first-degree relatives of BD patients may help to distinguish structural biomarkers of genetic risk without the confounding effects of burden of illness, medication or clinical state. In the present study, we applied tract-based spatial statistics to study WM changes in patients with BD, unaffected siblings and controls.MethodA total of 27 euthymic patients with BD type I, 20 unaffected siblings of bipolar patients and 29 healthy controls who did not have any current or past diagnosis of Axis I psychiatric disorders were enrolled in the study.ResultsFractional anisotropy (FA) was significantly lower in BD patients than in the control group in the corpus callosum, fornix, bilateral superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, anterior thalamic radiation, posterior thalamic radiation, cingulum, uncinate fasciculus, superior corona radiata, anterior corona radiata and left external capsule. In region-of-interest (ROI) analyses, we found that both unaffected siblings and bipolar patients had significantly reduced FA in the left posterior thalamic radiation, the left sagittal stratum, and the fornix compared with healthy controls. Average FA for unaffected siblings was intermediate between the healthy controls and bipolar patients within these ROIs.ConclusionsDecreased FA in the fornix, left posterior thalamic radiation and left sagittal stratum in both bipolar patients and unaffected siblings may represent a potential structural endophenotype or a trait-based marker for BD.

scholarly journals Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression

2020 ◽  
Vol 9 ◽  
Author(s):  
Fariba Mahmoudi ◽  
Khadijeh Haghighat Gollo
Keyword(s):  
Gene Expression ◽  
Saline Group ◽  
Polymerase Chain Reaction Method ◽  
Male Rats ◽  
Expression Levels ◽  
Serum Lh ◽  
Genes Expression ◽  
Lh Release ◽  
The Mean ◽  
Gene Expression Levels

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and  KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.[GMJ.2020;9:e1767]

scholarly journals Markers of Regenerative Processes in Patients with Bipolar Disorder: A Case-control Study

2020 ◽  
Vol 10 (7) ◽  
pp. 408
Author(s):  
Artur Reginia ◽  
Jerzy Samochowiec ◽  
Marcin Jabłoński ◽  
Ewa Ferensztajn-Rochowiak ◽  
Janusz K. Rybakowski ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Medical Science ◽  
Lithium Salts ◽  
Stable Phase ◽  
Control Group ◽  
Type I ◽  
Healthy Controls ◽  
Regenerative Processes ◽  
Factors Affecting ◽  
Socio Demographic Factors

Progress in medical science has allowed the discovery of many factors affecting the pathogenesis of bipolar disorder, and among the most recent research directions are found regenerative and inflammatory processes. The role of regenerative processes remains particularly poorly explored, but available data encourage further research, which may explain the pathogenesis of bipolar disorder (BD). The aim of this study was to evaluate the mobilization of stem cells into peripheral blood, in patients with bipolar disorder during stable phase, not treated with lithium salts. The study included 30 unrelated individuals with the diagnosis of bipolar disorder, with disease duration of at least 10 years, not treated with lithium salts for at least five years prior to the study. The control group consisted of 30 healthy subjects, matched for age, sex, body mass index (BMI), origin, socio-demographic factors and nicotine use. Blood samples underwent cytometric analyses to assess concentrations of: Very Small Embryonic Like (VSEL) CD34+, VSEL AC133+, HSC CD34+, HSC AC133+. There were no significant differences in stem cell levels between patients with BD and healthy controls. However, the level of VSEL cells AC133 + was significantly higher in type I BD patients compared to healthy controls. Our results indicate a disturbance in regenerative processes in patients with bipolar disorder.

scholarly journals Immune Condition of Colorectal Cancer Patients Featured by Serum Chemokines and Gene Expressions of CD4+ Cells in Blood

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Takuya Komura ◽  
Masaaki Yano ◽  
Akimitsu Miyake ◽  
Hisashi Takabatake ◽  
Masaki Miyazawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Blood Parameters ◽  
Healthy Controls ◽  
Cd4 Cells ◽  
Gene Expressions ◽  
Expression Levels ◽  
Cd8 Cells

Background. Colorectal cancer (CRC), the most common malignancy worldwide, causes inflammation. We explored the inflammatory pathophysiology of CRC by assessing the peripheral blood parameters. Methods. The differences in gene expression profiles of whole blood cells and cell subpopulations between CRC patients and healthy controls were analyzed using DNA microarray. Serum cytokine/chemokine concentrations in CRC patients and healthy controls were measured via multiplex detection immunoassays. In addition, we explored correlations between the expression levels of certain genes of peripheral CD4+ cells and serum chemokine concentrations. Results. The gene expression profiles of peripheral CD4+ cells of CRC patients differed from those of healthy controls, but this was not true of CD8+ cells, CD14+ cells, CD15+ cells, or CD19+ cells. Serum IL-8 and eotaxin-1 levels were significantly elevated in CRC patients, and the levels substantially correlated with the expression levels of certain genes of CD4+ cells. Interestingly, the relationships between gene expression levels in peripheral CD4+ cells and serum IL-8 and eotaxin-1 levels resembled those of monocytes/macrophages, not T cells. Conclusions. Serum IL-8 and eotaxin-1 concentrations increased and were associated with changes in the gene expression of peripheral CD4+ cells in CRC patients.

scholarly journals VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

2016 ◽  
Vol 209 (2) ◽  
pp. 114-120 ◽  
Author(s):  
Martin Tesli ◽  
Katrine Verena Wirgenes ◽  
Timothy Hughes ◽  
Francesco Bettella ◽  
Lavinia Athanasiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Association Studies ◽  
Mrna Level ◽  
Genome Wide Association Studies ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Schizophrenia Spectrum Disorders ◽  
Underlying Mechanisms

BackgroundCommon variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.AimsTo identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.MethodVRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.ResultsWe found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10–12), bipolar disorder (P<10–12) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.ConclusionsAltered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.

scholarly journals Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response

2013 ◽  
Vol 44 (3) ◽  
pp. 507-517 ◽  
Author(s):  
T. Hajek ◽  
M. Bauer ◽  
C. Simhandl ◽  
J. Rybakowski ◽  
C. O'Donovan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Treatment Response ◽  
Brain Structure ◽  
Neuroprotective Effect ◽  
Mood Stabilizer ◽  
Term Treatment ◽  
Healthy Controls ◽  
Neuroprotective Effects ◽  
Long Term Treatment

BackgroundNeuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).MethodTo address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.ResultsThe non-Li group had smaller hippocampal volumes than the controls or the Li group (F2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t51 = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t43 = 2.62, corrected p = 0.02).ConclusionsOur findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.

scholarly journals Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder type I, type II, unaffected siblings and healthy controls

2018 ◽  
Vol 213 (3) ◽  
pp. 548-554 ◽  
Author(s):  
Sonya F. Foley ◽  
Matthew Bracher-Smith ◽  
Katherine E. Tansey ◽  
Judith R. Harrison ◽  
Greg D. Parker ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Fractional Anisotropy ◽  
Type I ◽  
Healthy Controls ◽  
Type Ii ◽  
Uncinate Fasciculus ◽  
Polygenic Risk ◽  
The Right ◽  
Main Effects ◽  
Disorder Type

BackgroundFractional anisotropy in the uncinate fasciculus and the cingulum may be biomarkers for bipolar disorder and may even be distinctly affected in different subtypes of bipolar disorder, an area in need of further research.AimsThis study aims to establish if fractional anisotropy in the uncinate fasciculus and cingulum shows differences between healthy controls, patients with bipolar disorder type I (BD-I) and type II (BD-II), and their unaffected siblings.MethodFractional anisotropy measures from the uncinate fasciculus, cingulum body and parahippocampal cingulum were compared with tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD-II.ResultsThe main effects were found in both the right and left uncinate fasciculus, with patients with BD-I showing significantly lower fractional anisotropy than both patients with BD-II and healthy controls. Participants with BD-II did not differ from healthy controls. Siblings showed similar effects in the left uncinate fasciculus. In a subsequent complementary analysis, we investigated the association between fractional anisotropy in the uncinate fasciculus and polygenic risk for bipolar disorder and psychosis in a large cohort (n= 570) of healthy participants. However, we found no significant association.ConclusionsFractional anisotropy in the uncinate fasciculus differs significantly between patients with BD-I and patients with BD-II and healthy controls. This supports the hypothesis of differences in the physiological sub-tract between bipolar disorder subtypes. Similar results were found in unaffected siblings, suggesting the potential for this biomarker to represent an endophenotype for BD-I. However, fractional anisotropy in the uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or psychosis.Declaration of interestNone.

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