Testing frameworks for personalizing bipolar disorder.
Ontology highlight
ABSTRACT:
SUBMITTER: Cochran AL
PROVIDER: S-EPMC5804032 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
Publications
Testing frameworks for personalizing bipolar disorder.
Cochran Amy L AL Schultz André A McInnis Melvin G MG Forger Daniel B DB
Translational psychiatry 20180202 1
The hallmark of bipolar disorder is a clinical course of recurrent manic and depressive symptoms of varying severity and duration. Mathematical modeling of bipolar disorder holds the promise of an ability to personalize diagnoses, to predict future mood episodes, to directly compare diverse datasets, and to link basic mechanisms to behavioral data. Several modeling frameworks have been proposed for bipolar disorder, which represent competing hypothesis about the basic framework of the disorder. ...[more]
Similar Datasets
Project description:Background:Bipolar disorder (BD) is a frequent cause of disability, health care costs, and risk of suicide. Pharmacogenetic tests (PGTs) could help clinicians to identify those patients predisposed to the occurrence of adverse events (AEs) improving the understanding of the correlation between genetic variants and drug response. Materials and methods:The study evaluated 30 patients affected by BD type I or II (according to Diagnostic and Statistical Manual of Mental Disorders, version 5) who underwent the PGT Neurofarmagen® (AB-BIOTICS SA, Barcelona, Spain) between March 2016 and March 2017. The primary aim of this study was to identify if the treatment prescribed by the psychiatrists was consistent with the treatment suggested by the PGT at T0 (corresponding to the test report communication). As a secondary aim, we wanted to assess if clinicians had changed the treatment (in case of discordance) at T1 (3-month follow-up visit) according to the results of the PGT. Results:At T0, only 4 patients (13%) had an optimal therapy in line with the PGT suggestions. At 3-month follow-up, 13 patients (40%) had received a change of therapy consistent to the test, showing a significant statistical improvement in the Clinical Global Impression item Severity (CGI-S) score over time compared to those not having changes consistent with the test. Regarding AEs, at baseline 9 out of 10 (90%) of the patients who received a therapy modification according to the test presented AEs, and a significant within-group reduction was observed after 3 months (p = 0.031). Conclusion:Despite the small sample size, the study shows promising data about the usefulness of PGT to support clinicians in reaching a more effective and tolerated treatment in the routine approach of BD.
| S-EPMC5860421 | biostudies-literature
Project description:ObjectiveBipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages.MethodsUsing retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2-4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates.ResultsFive years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex.ConclusionsStaging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified.
| S-EPMC6590317 | biostudies-literature
Project description:Introduction:Pharmacogenetic testing may assist in identifying an individual's risk of developing a mental illness as well as predict an individual's response to treatment. The objective of this study is to report published outcomes of pharmacogenetic testing in patients with schizophrenia or bipolar disorder. Methods:A systematic review using PubMed and EBSCOhost through April 2017 was performed to identify articles that reported pharmacogenetic testing in adult patients with either bipolar disorder or schizophrenia using the keywords pharmacy, pharmacogenomics, pharmacogenetics, psychiatry, bipolar disorder, schizophrenia, mood stabilizer, and antipsychotic. Results:A total of 18 articles were included in the final literature review. A wide variety of genes amongst adult patients with varying ethnicities were found to be correlated with the development of schizophrenia or bipolar disorder as well as response to antipsychotics and mood stabilizers. Discussion:While current studies show a correlation between genetic variations and medication response or disease predisposition for patients with schizophrenia and bipolar disorder, research is unclear on the type of therapeutic recommendations that should occur based on the results of the pharmacogenetic testing. Hopefully interpreting pharmacogenetic results will one day assist with optimizing medication recommendations for individuals with schizophrenia and bipolar disorder.
| S-EPMC6213894 | biostudies-literature
Project description:PurposeThis review article introduces research methods for personalization of intervention. Our goals are to review evidence-based practices for improving social communication impairment in children with autism spectrum disorder generally and then how these practices can be systematized in ways that personalize intervention, especially for children who respond slowly to an initial evidence-based practice.MethodThe narrative reflects on the current status of modular and targeted interventions on social communication outcomes in the field of autism research. Questions are introduced regarding personalization of interventions that can be addressed through research methods. These research methods include adaptive treatment designs and the Sequential Multiple Assignment Randomized Trial. Examples of empirical studies using research designs are presented to answer questions of personalization.ConclusionBridging the gap between research studies and clinical practice can be advanced by research that attempts to answer questions pertinent to the broad heterogeneity in children with autism spectrum disorder, their response to interventions, and the fact that a single intervention is not effective for all children.Presentation videohttps://doi.org/10.23641/asha.7298021.
| S-EPMC6693574 | biostudies-literature
Project description:Purpose of study is revealing significant differences in serum proteomes in schizophrenia, bipolar disorder (BD), and matched healthy controls. The sample preparation included affinity removing of six major proteins, separation by 1D electrophoresis, in-gel tryptic hydrolysis, and LC-MS/MS peptide analysis using LTQ Orbitrap Velos mass spectrometer. When comparing proteome profiles, different unique protein sets were revealed (absent in other groups): 22 proteins typical for schizophrenia, and 20 – for BD. Protein set in schizophrenia was mostly associated with nucleic acid and protein metabolism, immune response, cell communication, and cell growth and maintenance. Protein set in BD was mostly associated with cell growth and maintenance, nucleic acid metabolism regulation, immune response, protein metabolism, transport and cell communication. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12), coagulation factor XIII, and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration (p=0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly (p=0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71;7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001;4.11] ng/ml). Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders.
2019-11-12 | PXD009219 | Pride
Project description:BackgroundPatient surveillance using repeated biomarker measurements presents an opportunity to detect and treat disease progression early. Frequent surveillance testing using biomarkers is recommended and routinely conducted in several diseases, including cancer and diabetes. However, frequent testing involves tradeoffs. Although surveillance tests provide information about current disease status, the complications and costs of frequent tests may not be justified for patients who are at low risk of progression. Predictions based on patients' earlier biomarker values may be used to inform decision making; however, predictions are uncertain, leading to decision uncertainty.MethodsWe propose the Personalized Risk-Adaptive Surveillance (PRAISE) framework, a novel method for embedding predictions into a value-of-information (VOI) framework to account for the cost of uncertainty over time and determine the time point at which collection of biomarker data would be most valuable. The proposed sequential decision-making framework is innovative in that it leverages the patient's longitudinal history, considers individual benefits and harms, and allows for dynamic tailoring of surveillance intervals by considering the uncertainty in current information and estimating the probability that new information may change treatment decisions, as well as the impact of this change on patient outcomes.ResultsWhen applied to data from cystic fibrosis patients, PRAISE lowers costs by allowing some patients to skip a visit, compared to an "always test" strategy. It does so without compromising expected survival, by recommending less frequent testing among those who are unlikely to be treated at the skipped time point.ConclusionsA VOI-based approach to patient monitoring is feasible and could be applied to several diseases to develop more cost-effective and personalized strategies for ongoing patient care.HighlightsIn many patient-monitoring settings, the complications and costs of frequent tests are not justified for patients who are at low risk of disease progression. Predictions based on patient history may be used to individualize the timing of patient visits based on evolving risk.We propose Personalized Risk-Adaptive Surveillance (PRAISE), a novel method for personalizing the timing of surveillance testing, where prediction modeling projects the disease trajectory and a value-of-information (VOI)-based pragmatic decision-theoretic framework quantifies patient- and time-specific benefit-harm tradeoffs.A VOI-based approach to patient monitoring could be applied to several diseases to develop more personalized and cost-effective strategies for ongoing patient care.
| S-EPMC9007840 | biostudies-literature
Project description:ObjectiveBipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR).MethodDuring functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth.ResultsWe found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction).ConclusionIf replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177.
| S-EPMC9382574 | biostudies-literature
Project description:BackgroundBipolar disorder (BD) affects both sexes, but important sex differences exist with respect to its symptoms and comorbidities. For example, rapid cycling (RC) is more prevalent in females, and alcohol use disorder (AUD) is more prevalent in males. We hypothesize that X chromosome variants may be associated with sex-specific characteristics of BD. Few studies have explored the role of the X chromosome in BD, which is complicated by X chromosome inactivation (XCI). This process achieves "dosage compensation" for many X chromosome genes by silencing one of the two copies in females, and most statistical methods either ignore that XCI occurs or falsely assume that one copy is inactivated at all loci. We introduce new statistical methods that do not make these assumptions.MethodsWe investigated this hypothesis in 1001 BD patients from the Genetic Association Information Network (GAIN) and 957 BD patients from the Mayo Clinic Bipolar Disorder Biobank. We examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI. In the "XCI-informed approach," we fit a sex-adjusted logistic regression model assuming additive genetic effects where we coded the SNP either assuming one copy is expressed or two copies are expressed based on prior knowledge about which regions are inactivated. In the "XCI-robust approach," we fit a logistic regression model with sex, SNP, and SNP-sex interaction effects that is flexible to whether the region is inactivated or escaping XCI.ResultsUsing the "XCI-informed approach," which considers only the main effect of SNP and does not allow the SNP effect to differ by sex, no significant associations were identified for any of the phenotypes. Using the "XCI-robust approach," intergenic SNP rs5932307 was associated with BD (P = 8.3 × 10-8), with a stronger effect in females (odds ratio in males (ORM) = 1.13, odds ratio in females for a change of two allele copies (ORW2) = 3.86).ConclusionX chromosome association studies should employ methods which account for its unique biology. Future work is needed to validate the identified associations with BD, to formally assess the performance of both approaches under different true genetic architectures, and to apply these approaches to study sex differences in other conditions.
| S-EPMC6902568 | biostudies-literature
Project description:Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.
| S-EPMC1180589 | biostudies-literature
Project description:Asenapine (Saphris(®)) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.
| S-EPMC4675633 | biostudies-literature