scholarly journals Alu element in the RNA binding motif protein, X-linked 2 (RBMX2) gene found to be linked to bipolar disorder

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261170
Author(s):  
Pia Laine ◽  
William J. Rowell ◽  
Lars Paulin ◽  
Steve Kujawa ◽  
Denise Raterman ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Tandem Repeat ◽  
Rna Binding ◽  
Extended Family ◽  
Coagulation Factor ◽  
Binding Motif ◽  
Type I ◽  
Increased Risk ◽  
Protein X ◽  
Disease Haplotype

Objective We have used long-read single molecule, real-time (SMRT) sequencing to fully characterize a ~12Mb genomic region on chromosome Xq24-q27, significantly linked to bipolar disorder (BD) in an extended family from a genetic sub-isolate. This family segregates BD in at least four generations with 24 affected individuals. Methods We selected 16 family members for targeted sequencing. The selected individuals either carried the disease haplotype, were non-carriers of the disease haplotype, or served as married-in controls. We designed hybrid capture probes enriching for 5-9Kb fragments spanning the entire 12Mb region that were then sequenced to screen for candidate structural variants (SVs) that could explain the increased risk for BD in this extended family. Results Altogether, 201 variants were detected in the critically linked region. Although most of these represented common variants, three variants emerged that showed near-perfect segregation among all BD type I affected individuals. Two of the SVs were identified in or near genes belonging to the RNA Binding Motif Protein, X-Linked (RBMX) gene family—a 330bp Alu (subfamily AluYa5) deletion in intron 3 of the RBMX2 gene and an intergenic 27bp tandem repeat deletion between the RBMX and G protein-coupled receptor 101 (GPR101) genes. The third SV was a 50bp tandem repeat insertion in intron 1 of the Coagulation Factor IX (F9) gene. Conclusions Among the three genetically linked SVs, additional evidence supported the Alu element deletion in RBMX2 as the leading candidate for contributing directly to the disease development of BD type I in this extended family.

Evidence towards RNA Binding Motif (RNP1, RRM) Protein 3 (RBM3) as a Potential Biomarker of Lithium Response in Bipolar Disorder Patients

2017 ◽  
Vol 62 (3-4) ◽  
pp. 304-308 ◽  
Author(s):  
Eleni Merkouri Papadima ◽  
Paola Niola ◽  
Carla Melis ◽  
Claudia Pisanu ◽  
Donatella Congiu ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rna Binding ◽  
Binding Motif ◽  
Potential Biomarker ◽  
Lithium Response

Treatment implications for bipolar disorder co-occurring with anxiety syndromes and substance abuse

2017 ◽  
Author(s):  
Gustavo H. Vázquez ◽  
Alberto Forte ◽  
Sebastián Camino ◽  
Leonardo Tondo ◽  
Ross J. Baldessarini
Keyword(s):  
Bipolar Disorder ◽  
Substance Abuse ◽  
Clinical Care ◽  
Adverse Outcomes ◽  
Type I ◽  
Post Traumatic Stress ◽  
Obsessive Compulsive ◽  
Increased Risk ◽  
Emerging Treatments ◽  
Post Traumatic

Anxiety symptoms and syndromes affect approximately half of both types I and II bipolar disorder (BD) patients at some time, more in women than men. Reported prevalence has ranked: generalized anxiety ≥ phobias ≥ panic ≥ post-traumatic stress syndrome ≥ obsessive–compulsive syndrome. BD associated with anxiety disorders is less responsive to mood-stabilizing treatments, with greater disability, substance abuse, and possibly suicidal risk. Emerging treatments for anxiety in BD patients include lurasidone, olanzapine, quetiapine, valproate, and psychotherapies, whereas the efficacy and safety of standard anxiolytics and antidepressants are not established. Abuse of alcohol, cannabis, stimulants, and opioids, alone or in combinations, also affects about half of BD patients at some time—more men than women and possibly somewhat more in type I than II. Substance abuse greatly complicates clinical care, contributing to erratic treatment-adherence, adverse outcomes, disability, increased risk of suicide or accidental death, and increased costs of care and from disability.

scholarly journals Cleavage of Interferon Regulatory Factor 7 by Enterovirus 71 3C Suppresses Cellular Responses

2012 ◽  
Vol 87 (3) ◽  
pp. 1690-1698 ◽  
Author(s):  
Xiaobo Lei ◽  
Xia Xiao ◽  
Qinghua Xue ◽  
Qi Jin ◽  
Bin He ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Rna Binding ◽  
Rna Virus ◽  
Ectopic Expression ◽  
Enterovirus 71 ◽  
Cellular Responses ◽  
Binding Motif ◽  
Type I ◽  
Amino Terminal ◽  
Amino Terminal Domain

ABSTRACTEnterovirus 71 (EV71) is a positive-stranded RNA virus which is capable of inhibiting innate immunity. Among virus-encoded proteins, the 3C protein compromises the type I interferon (IFN-I) response mediated by retinoid acid-inducible gene-I (RIG-I) or Toll-like receptor 3 that activates interferon regulatory 3 (IRF3) and IRF7. In the present study, we report that enterovirus 71 downregulates IRF7 through the 3C protein, which inhibits the function of IRF7. When expressed in mammalian cells, the 3C protein mediates cleavage of IRF7 rather than that of IRF3. This process is insensitive to inhibitors of caspase, proteasome, lysosome, and autophagy. H40D substitution in the 3C active site abolishes its activity, whereas R84Q or V154S substitution in the RNA binding motif has no effect. Furthermore, 3C-mediated cleavage occurs at the Q189-S190 junction within the constitutive activation domain of IRF7, resulting in two cleaved IRF7 fragments that are incapable of activating IFN expression. Ectopic expression of wild-type IRF7 limits EV71 replication. On the other hand, expression of the amino-terminal domain of IRF7 enhances EV71 infection, which correlates with its ability to interact with and inhibit IRF3. These results suggest that control of IRF7 by the 3C protein may represent a viral mechanism to escape cellular responses.

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.

scholarly journals Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 348
Author(s):  
Francesco Menzella ◽  
Giulia Ghidoni ◽  
Carla Galeone ◽  
Silvia Capobelli ◽  
Chiara Scelfo ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Severe Asthma ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Antiviral Effect ◽  
Point Of View ◽  
Type I ◽  
Effector Cells ◽  
Viral Spread ◽  
Increased Risk

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.

scholarly journals Deficits in explicit emotion regulation in bipolar disorder: a systematic review

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marcel Kurtz ◽  
Pia Mohring ◽  
Katharina Förster ◽  
Michael Bauer ◽  
Philipp Kanske
Keyword(s):  
At Risk ◽  
Bipolar Disorder ◽  
Emotion Regulation ◽  
Mood State ◽  
Bipolar Disorders ◽  
Protective Measure ◽  
Behavioral Measures ◽  
Increased Risk ◽  
Regulation Strategies ◽  
Depressive Episodes

Abstract Background This study aimed to compile and synthesize studies investigating explicit emotion regulation in patients with bipolar disorder and individuals at risk of developing bipolar disorder. The importance of explicit emotion regulation arises from its potential role as a marker for bipolar disorders in individuals at risk and its potent role in therapy for bipolar disorder patients. Methods To obtain an exhaustive compilation of studies dealing specifically with explicit emotion regulation in bipolar disorder, we conducted a systematic literature search in four databases. In the 15 studies we included in our review, the emotion-regulation strategies maintenance, distraction, and reappraisal (self-focused and situation-focused) were investigated partly on a purely behavioral level and partly in conjunction with neural measures. The samples used in the identified studies included individuals at increased risk of bipolar disorder, patients with current affective episodes, and patients with euthymic mood state. Results In summary, the reviewed studies' results indicate impairments in explicit emotion regulation in individuals at risk for bipolar disorder, patients with manic and depressive episodes, and euthymic patients. These deficits manifest in subjective behavioral measures as well as in neural aberrations. Further, our review reveals a discrepancy between behavioral and neural findings regarding explicit emotion regulation in individuals at risk for bipolar disorders and euthymic patients. While these groups often do not differ significantly in behavioral measures from healthy and low-risk individuals, neural differences are mainly found in frontostriatal networks. Conclusion We conclude that these neural aberrations are a potentially sensitive measure of the probability of occurrence and recurrence of symptoms of bipolar disorders and that strengthening this frontostriatal route is a potentially protective measure for individuals at risk and patients who have bipolar disorders.

scholarly journals The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rona J. Strawbridge ◽  
Keira J. A. Johnston ◽  
Mark E. S. Bailey ◽  
Damiano Baldassarre ◽  
Breda Cullen ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
European Ancestry ◽  
Cardiometabolic Disease ◽  
Metabolic Profiles ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Major Depressive ◽  
Increased Risk

AbstractUnderstanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.

scholarly journals The functional impairment of different subtypes and occupational states in euthymic patients with bipolar disorder

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xinyu Liu ◽  
Xiaojuan Ma ◽  
Wenchen Wang ◽  
Jian Zhang ◽  
Xia Sun ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Social Functioning ◽  
Rating Scale ◽  
Verbal Learning ◽  
Occupational Status ◽  
Learning Performance ◽  
Neurocognitive Functioning ◽  
Type I ◽  
Speed Of Processing ◽  
Occupational Functioning

Abstract Background The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients. Methods A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively. Results Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups. Conclusion Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.

scholarly journals The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 883
Author(s):  
Anna Gaertner ◽  
Julia Bloebaum ◽  
Andreas Brodehl ◽  
Baerbel Klauke ◽  
Katharina Sielemann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Early Onset ◽  
Target Genes ◽  
Frameshift Mutation ◽  
Rna Binding ◽  
Splicing Factor ◽  
Binding Motif ◽  
Rich Domain ◽  
Generation Sequencing

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them TTN and RBM20. Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in TTN (TTNtv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 (RBM20) are also known to be associated with severe cardiomyopathies. TTN is one of the major RBM20 splicing targets. Most of the pathogenic RBM20 mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant RBM20. Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic TTN and RBM20 mutations. We show that the splicing of RBM20 target genes is affected in the mutation carrier. Furthermore, we reveal RBM20 haploinsufficiency presumably caused by the frameshift mutation in RBM20.

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