Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran

2020 ◽  
Vol 21 (14) ◽  
pp. 1011-1020
Author(s):  
Sara Sadat Aghabozorg Afjeh ◽  
Jamal Shams ◽  
Safar Hamednia ◽  
Behzad Boshehri ◽  
Amir Olfat ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Suicide Ideation ◽  
Lithium Carbonate ◽  
Predictive Biomarker ◽  
Amplification Refractory Mutation System ◽  
Cerebral Endothelium ◽  
Mutation System ◽  
Bipolar Patients ◽  
The Impact

High rates of mortality due to both suicide and medical comorbidities in bipolar patients can be decreased through the administration of lithium, which affects the cerebral endothelium as well as neurons. To investigate the role of ADCY2 in risk of bipolar disorder, we genotyped the ADCY2 rs2290910 in bipolar patients and healthy controls using amplification refractory mutation system PCR. This polymorphism was associated with risk of bipolar disorder (odds ratio [OR]: 0.430; 95% CI: 0.296–0.624; p = 0.001). The C allele was more frequent in suicide ideation group compared other groups (OR: 2.7; 95% CI: 1.386–5.302; p = 0.004). The T allele was more frequent in suicide attempt group compared with suicide ideation group (OR: 0.238; 95% CI: 0.111–0.509; p = 0.001).

Impulsivity predicts illness severity in long-term course of bipolar disorder: A prospective approach

2018 ◽  
Vol 52 (9) ◽  
pp. 876-886 ◽  
Author(s):  
Jonas Rote ◽  
Alice-Mai-Ly Dingelstadt ◽  
Annette Aigner ◽  
Michael Bauer ◽  
Jana Fiebig ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Linear Regression Analysis ◽  
Age At Onset ◽  
Illness Severity ◽  
Observation Time ◽  
Barratt Impulsiveness Scale ◽  
Trait Impulsivity ◽  
Morbidity Index ◽  
Bipolar Patients ◽  
The Impact

Background: Bipolar disorder is a common, severe and chronic mental illness. Despite this, predictors of illness severity remain poorly understood. Impulsivity is reported to be associated with bipolar disorder and aggravating comorbidities. This study therefore sought to examine the predictive value of impulsivity for determining illness severity in euthymic bipolar disorder patients. Methods: Baseline trait impulsivity of 120 bipolar euthymic patients (81 bipolar disorder I [68%], 80 female [67%]) and 51 healthy controls was assessed using Barratt Impulsiveness Scale 11. The impact of impulsivity on illness severity (measured with morbidity index) was prospectively tested in 97 patients with sufficient follow-up data (average observation time: 54.4 weeks), using linear regression analysis. Results: Barratt Impulsiveness Scale 11 total (β = 0.01; p < 0.01) and in particular Barratt Impulsiveness Scale 11 attentional subscale scores (β = 0.04; p < 0.001) predicted illness severity in bipolar disorder, while controlling for other clinical variables. Only age at onset persisted as an additional, but less influential predictor. Barratt Impulsiveness Scale 11 total scores and Barratt Impulsiveness Scale 11 attentional subscale scores were significantly higher in euthymic patients compared to controls. This was not observed for the motor or non-planning subscale scores. Limitations: The average year-long observation time might not be long enough to account for the chronic course of bipolar disorder. Conclusion: Trait impulsivity and particularly attentional impulsivity in euthymic bipolar patients can be strong predictors of illness severity in bipolar disorder. Future studies should explore impulsivity as a risk assessment for morbidity and as a therapeutic target in bipolar disorder patients.

Preemptive NUDT15 genotyping: redefining the management of patients with thiopurine-induced toxicity

2018 ◽  
Vol 33 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Swarup A.V. Shah ◽  
Minal U. Paradkar ◽  
Devendra C. Desai ◽  
Tester F. Ashavaid
Keyword(s):  
Strong Association ◽  
Amplification Refractory Mutation System ◽  
Dose Requirement ◽  
Asian Patients ◽  
Thiopurine Therapy ◽  
Individual Variations ◽  
Significant Difference ◽  
Mutation System ◽  
Risk Patients

AbstractBackground:Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between theNUDT15gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of theNUDT15variant (C415T) in Indian patients on thiopurine therapy.Methods:NUDT15andTPMTgenotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique.Results:Of 370 samples received forTPMTtesting, 206 samples were available forNUDT15genotyping. TheNUDT15risk allele frequency was 10.7%, with the frequency of wild, heterozygous and mutant genotypes being 80.6%, 17.5% and 1.9%, respectively.TPMTvariants were seen in 13 of 370 (3.5%) patients, whereas theNUDT15variant was seen in 40 of 206 (19.4%) patients. Thiopurine-induced toxicity information was available for 101 patients, among whom 10 developed leukopenia and all harbored theNUDT15variant (p<0.0001).NUDT15was clinically more relevant thanTPMTin terms of sensitivity and specificity, as well as with a statistically significant difference in thiopurine dose requirement for patients with theNUDT15variant.Conclusions:A preemptiveNUDT15genotyping approach can therefore help identify high-risk patients (NUDT15C415T positive) who could benefit from thiopurine dose reduction, thereby preventing fatal thiopurine-induced toxicity.

scholarly journals PP029 Hospitalizations And Costs In Bipolar Disorder Patients Initiating Long-acting Injectable Antipsychotics

2017 ◽  
Vol 33 (S1) ◽  
pp. 83-83
Author(s):  
Mallik Greene ◽  
Tingjian Yan ◽  
Eunice Chang ◽  
Ann Hartry ◽  
Michael Broder
Keyword(s):  
Bipolar Disorder ◽  
Reference Group ◽  
Cohort Analysis ◽  
Linear Regression Models ◽  
Inpatient Hospitalization ◽  
Inpatient Hospitalizations ◽  
Long Acting ◽  
Bipolar Patients ◽  
The Impact

INTRODUCTION:Existing studies have not investigated the effectiveness of one long-acting injectable antipsychotic (LAI) versus another in preventing hospitalizations among patients with bipolar disorder (BD). This study was conducted to compare all-cause inpatient healthcare utilization and associated costs among BD patients who initiated LAIs.METHODS:This retrospective cohort analysis used the Truven Health Analytics MarketScan® Commercial and Medicaid claims database. Bipolar patients >18 years with at least one claim for one of the following LAIs were identified between 1 January 2013 and 30 June 2014 (identification period): aripiprazole, haloperidol, paliperidone, and risperidone. The first day of initiating an LAI was considered the index date. Logistic regression and generalized linear regression models were conducted to estimate risk of inpatient hospitalization and associated costs during the 1-year follow up.RESULTS:A total of 1,540 BD patients initiated an LAI: 14.5 percent aripiprazole, 16.3 percent risperidone, 21.0 percent haloperidol, and 48.1 percent paliperidone. With the aripiprazole cohort as the reference group, the odds of having any inpatient hospitalizations were significantly higher in haloperidol [Odds Ratio, OR (95 percent Confidence Interval, CI): 1.49 (1.01 - 2.19)] and risperidone [1.78 (1.19 - 2.66)] cohorts. The paliperidone cohort also had a higher risk of having a hospitalization than aripiprazole, but the difference was not statistically significant (p>.05). Among LAI initiators having any inpatient hospitalizations, the adjusted mean all-cause inpatient costs were lowest in the aripiprazole cohort (USD26,002), followed by risperidone (USD27,937), haloperidol (USD30,411), and paliperidone (USD33,240). However, the cost difference was not statistically significant.CONCLUSIONS:Our study findings highlight the value of aripiprazole in reducing all-cause inpatient hospitalizations and associated costs among patients with BD during the 1-year follow-up. It is worthwhile to note that bipolar diagnoses were identified from healthcare claims coded for reimbursement purposes, thus misclassification was possible. Future studies are warranted to understand the impact of LAI use in a longer period of time.

The Expanding Role of Antipsychotics

CNS Spectrums ◽  
2004 ◽  
Vol 9 (S1) ◽  
pp. 7-12
Author(s):  
Philip G. Janicak
Keyword(s):  
Bipolar Disorder ◽  
Manic Episode ◽  
Acute Mania ◽  
Psychotic Symptoms ◽  
Primary Therapy ◽  
Obsessive Compulsive ◽  
Stabilizing Agent ◽  
Compulsive Disorder ◽  
Bipolar Patients

Antipsychotics have been utilized in the treatment of bipolar disorder for many decades and were the mainstay of treatment before lithium was reintroduced in the late 1960s. Today, many bipolar patients who present with psychotic features are misdiagnosed and prescribed an antipsychotic for another disorder. Estimates of psychotic symptoms in bipolar disorder, particularly during a manic episode, are ≥50% by clinical assessment and even higher by individual reports. Thus, antipsychotics are frequently used: as first treatment for psychosis not recognized as bipolar disorder, and as an adjunct to a mood-stabilizing agent in bipolars with psychotic symptoms.Most recently, antipsychotics have been examined for their mood-stabilizing properties as well (Slide 9). One may conceptualize using a selective serotonin reuptake inhibitor (SSRI) antidepressant for disorders such as panic disorder or obsessive-compulsive disorder, and using an antiepileptic as a mood-stabilizing agent; however, it is more difficult to accept that an agent approved for treatment of psychosis can be a primary therapy for bipolar disorder. Data from the monotherapy trials suggest that second-generation antipsychotics (SGAs) are at least as effective as lithium and valproic acid for acute mania. There is a very large database indicating that SGAs can be utilized as monotherapy for acute mania. However, there is limited data on the role of these agents in prevention of relapse and recurrence and in their efficacy for depression in the context of bipolar disorder. More studies will be needed to clarify whether SGAs should be used as monotherapy or whether they would be best used as augmenting agents in severe and psychotically manic or depressed patients.

Impaired recognition of happy facial expressions in bipolar disorder

2014 ◽  
Vol 26 (4) ◽  
pp. 253-259 ◽  
Author(s):  
Linette Lawlor-Savage ◽  
Scott R. Sponheim ◽  
Vina M. Goghari
Keyword(s):  
Bipolar Disorder ◽  
Emotion Recognition ◽  
Facial Expressions ◽  
Processing Speed ◽  
Facial Emotion Recognition ◽  
Facial Emotion ◽  
Recognition Ability ◽  
Recognition Condition ◽  
Bipolar Patients

BackgroundThe ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated.MethodsClinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control.ResultsBipolar patients’ overall facial recognition ability was unimpaired. However, patients’ specific ability to judge happy expressions under time constraints was impaired.ConclusionsFindings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted.

HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14616-e14616
Author(s):  
Francesco Sclafani ◽  
Amitesh Chandra Roy ◽  
Ian Chau ◽  
Andrew Wotherspoon ◽  
Clare Peckitt ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
Predictive Biomarker ◽  
Secondary Endpoints ◽  
Her 2 ◽  
Low Prevalence ◽  
The Impact

e14616 Background: HER-2 is a well established therapeutic target in breast and gastric cancer. The role of HER-2 in rectal cancer is unclear, as conflicting data on prevalence of HER-2 expression have been reported. Preclinical data indicate a potential role of HER-2 in mediating resistance of rectal cancer to chemoradiotherapy and cetuximab. This analysis evaluates the prevalence of HER-2 and its impact on the outcome of high risk rectal cancer patients treated with neoadjuvant CAPOX and CRT ± cetuximab in EXPERT-C. Methods: Eligible patients with available tumour tissue for HER-2 analysis were included. HER-2 expression was determined by immunohistochemistry (IHC) in biopsy and/or surgical specimens (score 0 to 3+). Tumours with equivocal IHC result (2+) were tested for HER-2 amplification by B-DISH. Tumours with IHC 3+ or B-DISH ratio ≥2.0 were classified as HER-2 positive. The impact of HER-2 on primary (CR) and secondary endpoints (RR, PFS, OS) of the study was analyzed. Results: Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3/104 (2.9%) and 3/114 (2.6%) were HER-2 positive, respectively. In 77 patients with paired specimens, concordance for HER-2 status was found in 74 (96%). Overall 141 patients were assessable for HER-2; 6/141 (4.3%) had a HER-2 positive tumour in at least 1 specimen. The median follow-up was 58.7 months. HER-2 expression or amplification was not associated with a difference in outcome for any of the study endpoints, including in the subset of 90 KRAS/BRAF wild type patients treated ± cetuximab. In an exploratory analysis, 44 IHC 0/1+ random specimens were tested by B-DISH and HER-2 amplification was found in 3/38 (7.9%, insufficient material in 6 cases). Conclusions: Based on the low prevalence of expression (according to the classical criteria for defining HER-2 positivity) as recorded in EXPERT-C, HER-2 does not appear to represent a useful therapeutic target for high risk rectal cancer. We did not confirm the role of HER-2 as prognostic factor or potential predictive biomarker for cetuximab-based treatment.

Studying Cytotoxic T-lymphocyte- Associated Antigen-4 (CTLA-4) gene Polymorphism in a Sample of Iraqi Women with Polycystic Ovarian Syndrome

2019 ◽  
pp. 1-6
Keyword(s):  
Gene Polymorphism ◽  
Polycystic Ovarian Syndrome ◽  
Cytotoxic T Lymphocyte ◽  
Reproductive Age ◽  
Amplification Refractory Mutation System ◽  
Low Grade ◽  
Metabolic Disturbances ◽  
Mutation System ◽  
Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) considers as the most common disorder among women during reproductive age. Its common features involve hyperandrogenism, chronic anovulation, and weight gain. Till now, the pathogenesis of PCOS stay unknown, and there is evidence considered PCOS as a low-grade inflammatory disease. Polycystic ovarian syndrome is associated with a variety of endocrine and metabolic disturbances. The present study was designed to detect the role of (CTLA-4) gene polymorphism (rs733618) with PCOS. A total of 60 PCOS patients and 30 healthy women, matching in average age and body mass index (BMI), were enrolled in this study. Patients with PCOS were attend to AL - Nahrain University High Institute for Infertility Assisted Reproductive Technology, in Baghdad between Septembers to December/2018. Blood samples were aspirated from both groups to detection (CTLA-4) gene polymorphism (rs733618) by tetra-primer amplification-refractory mutation system based on real time polymerase chain reaction (ARMS-qPCR). The obtained results revealed normal genotyping for both groups. The result of current study confirms that there is no role of (CTLA-4) gene polymorphism (rs 733618) in PCOS.

scholarly journals Gender Differences in Complete Blood Count and Inflammatory Ratios among Patients with Bipolar Disorder

2021 ◽  
Vol 11 (3) ◽  
pp. 363
Author(s):  
Laura Fusar-Poli ◽  
Andrea Amerio ◽  
Patriciu Cimpoesu ◽  
Pietro Grimaldi Filioli ◽  
Antimo Natale ◽  
...  
Keyword(s):  
Gender Differences ◽  
Bipolar Disorder ◽  
Blood Count ◽  
Complete Blood Count ◽  
Low Cost ◽  
Female Group ◽  
State Dependent ◽  
And Gender ◽  
Bipolar Patients

Background: Evidence suggested that inflammation may be involved in the etiopathogenesis of bipolar disorder (BD), a chronic psychiatric condition affecting around 2-3% of the general population. However, little is known regarding potential gender differences in peripheral biomarkers of BD, such as neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), and monocyte-to-lymphocyte (MLR) ratios. Methods: In total, 197 females and 174 males with BD in different phases (i.e., (hypo)mania, depression, euthymia) were recruited. A blood sample was drawn to perform a complete blood count (CBC). NLR, PLR, and MLR were subsequently calculated, and differences were computed according to the illness phase and gender. Results: PLR was consistently higher in (hypo)manic than depressed patients, in both males and females. No significant gender differences in PLR value were found when considering only (hypo)mania. Conversely, NLR was increased in (hypo)mania only among males, and gender differences were retrieved in the (hypo)manic subgroup. The findings related to MLR were only marginally significant. Higher platelets values were associated with (hypo)mania only in the female group. Basophils and eosinophils appeared gender- but not state-dependent. Conclusions: Our findings provide further evidence that increased PLR levels may be associated with (hypo)mania in bipolar patients, regardless of gender. Moreover, the usefulness of NLR as a peripheral biomarker of BD appeared limited to males while the role of platelets to females. As CBC represents a low-cost and easily accessible test, researchers should investigate in-depth its potential usefulness as a biomarker of BD and other psychiatric disorders.

Insanity defence in bipolar patients at the time of committing murder according to Iranian law: Case studies

2019 ◽  
Vol 88 (1) ◽  
pp. 24-29
Author(s):  
Azadeh Memarian ◽  
Seyed Hossein Moosavinezhad Baboli ◽  
Hanieh Saboori Shekofteh
Keyword(s):  
Bipolar Disorder ◽  
Social Media ◽  
Public Education ◽  
Forensic Psychiatry ◽  
Legal Responsibility ◽  
Criminal Behaviour ◽  
Iranian Law ◽  
The Family ◽  
Bipolar Patients

Bipolar disorder is a chronic, relapsing illness characterised by recurrent episodes of manic or depressive symptoms, with intervening periods that are relatively (but not fully) symptom-free. Studies have found higher rates of psychiatric disorders in homicide offenders than in the general population. The insanity defence is a legal construct that, under some circumstances, excuses defendants with mental illness from legal responsibility for criminal behaviour. Here we report two cases of family murder by the mother of the family caused by bipolar disease. The role of the forensic psychiatrist in diagnosing insanity during the commission of a crime is very important as these patients should be diagnosed, treated as soon as possible, and monitored. Public education through social media should be considered to reduce crimes in societies. Diagnosing insanity during the commission of a crime is very important and requires high precision forensic psychiatry. Public education through social media should be considered to reduce crimes in societies.

scholarly journals No Association ofPTGDR−441C/TPolymorphism with Asthma in a North Indian Population

2011 ◽  
Vol 31 (6) ◽  
pp. 353-359 ◽  
Author(s):  
Niti Birbian ◽  
Jagtar Singh ◽  
Surinder Kumar Jindal ◽  
Amit Joshi ◽  
Navneet Batra
Keyword(s):  
Indian Population ◽  
D2 Receptor ◽  
Promoter Polymorphism ◽  
North India ◽  
Amplification Refractory Mutation System ◽  
Prostaglandin D2 ◽  
North Indian Population ◽  
Mutation System ◽  
Prevalent Disease

Background:Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in thePTGDRgene have been suggested to be involved in the mechanism of asthma.Objective:This is the first study conducted in India, investigating the role ofPTGDR−441C/Tpromoter polymorphism in asthma pathogenesis.Methods:A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. ThePTGDR−441C/Tpolymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR).Results:Statistical analysis of the results between asthma cases and controls for thePTGDR−441C/Tpolymorphism showed Chi2(χ2) = 0.29, OR = 0.95, 95% CI (0.70–1.15) andp= 0.599. Neither the genotypic nor the allelic frequencies observed for thePTGDR−441C/Tpolymorphism, were significantly associated with asthma or asthma phenotypes.Conclusions:ThePTGDR−441C/Tpolymorphism is not associated with asthma or its phenotypes in the studied North Indian population.

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