The latest mania: selling bipolar disorder.
Ontology highlight
ABSTRACT:
SUBMITTER: Healy D
PROVIDER: S-EPMC1434505 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes. In total, 12 total RNA samples were used for microarray analysis: 6 samples from Madison mice and 6 samples from ICR outbred mice. All samples were biological replicates.
2012-05-03 | E-GEOD-29417 | biostudies-arrayexpress
Project description:Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.
2012-05-04 | GSE29417 | GEO
Project description:ObjectiveThe authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder.MethodUsing linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.ResultsPatients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted.ConclusionsNo evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
| S-EPMC6641557 | biostudies-literature
Project description:Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary rodent models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain termed Madison (MSN) that naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a novel genome enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Using a functional network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.
| S-EPMC3366954 | biostudies-literature
Project description:Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.
| S-EPMC5049992 | biostudies-literature
Project description:Evidence supporting the continuous latent structure of mood phenomena has not been incorporated into psychiatric diagnostic systems, in part because the evidence has been incomplete. For example, no studies have investigated the boundary between 'sick' and 'well' periods in individuals with bipolar disorder, despite agreement that characterization of mood disorders as having a discrete episodic course is inaccurate. The present study examined the validity of mood episode symptom thresholds in out-patients with bipolar disorder using multiple methodologies: taxometrics and information-theoretic latent distribution modeling (ITLDM), to evaluate the continuity/discontinuity of mood symptoms; and structural equation mixture modeling (SEMM), to evaluate the continuity/discontinuity of associations between mood symptoms and general functioning.A total of 3721 out-patients with bipolar disorder from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were available for analysis. Data were collected at participants' baseline STEP-BD visit. Taxometric [maximum covariance/means above minus below a cut (MAXCOV/MAMBAC) with simulated comparison data], ITLDM and SEMM methods were applied twice, once to the Montgomery-Åsberg Depression Rating Scale and again to the Young Mania Rating Scale.Taxometric results unequivocally supported a continuous interpretation of the data. ITLDM results favored many valued 'discrete metrical' models, suggesting that mood symptoms have continuous, but potentially non-normally distributed, latent structures in out-patients with bipolar disorder. Finally, SEMM results demonstrated that latent associations between mood symptoms and general functioning were linear.Results from the present study argue against the validity of DSM mood episode thresholds and argue for a graded continuum of care of bipolar symptom management.
| S-EPMC4751879 | biostudies-literature
Project description:The use of clinical features to define subtypes of a disorder may aid in gene identification for complex diseases. In particular, clinical subtypes of mania may distinguish phenotypic subgroups of bipolar subjects that may also differ genetically. To assess this possibility, we performed a genome-wide association study using genotype data from the Bipolar Genome Study (BiGS) and subjects that were categorized as having either irritable or elated mania during their most severe episode. A bipolar case-only analysis in the GAIN bipolar sample identified several genomic regions that differed between irritable and elated subjects, the most significant of which was for 33 SNPs on chromosome 13q31 (peak p?=?2×10(-7)). This broad peak is in a relative gene desert over an unknown EST and between the SLITRK1 and SLITRK6 genes. Evidence for association to this region came predominantly from subjects in the sample that were originally collected as part of a family-based bipolar linkage study, rather than those collected as bipolar singletons. We then genotyped an additional sample of bipolar singleton cases and controls, and the analysis of irritable vs. elated mania in this new sample did not replicate our previous findings. However, this lack of replication is likely due to the presence of significant differences in terms of clinical co-morbity that were identified between these singleton bipolar cases and those that were selected from families segregating the disorder. Despite these clinical differences, analysis of the combined sample provided continued support for 13q31 and other regions from our initial analysis. Though genome-wide significance was not achieved, our results suggest that irritable mania results from a distinct set of genes, including a region on chromosome 13q31.
| S-EPMC3542199 | biostudies-literature
Project description:ContextEarly identification of Bipolar Disorder (BD) remains poor despite the high levels of disability associated with the disorder.ObjectiveWe developed and evaluated a new DSM orientated scale for the identification of young people at risk for BD based on the Child Behavior Checklist (CBCL) and compared its performance against the CBCL-Pediatric Bipolar Disorder (CBCL-PBD) and the CBCL-Externalizing Scale, the two most widely used scales.MethodsThe new scale, CBCL-Mania Scale (CBCL-MS), comprises 19 CBCL items that directly correspond to operational criteria for mania. We tested the reliability, longitudinal stability and diagnostic accuracy of the CBCL-MS on data from the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective epidemiological cohort study of 2230 Dutch youths assessed with the CBCL at ages 11, 13 and 16. At age 19 lifetime psychiatric diagnoses were ascertained with the Composite International Diagnostic Interview. We compared the predictive ability of the CBCL-MS against the CBCL-Externalising Scale and the CBCL-PBD in the TRAILS sample.ResultsThe CBCL-MS had high internal consistency and satisfactory accuracy (area under the curve?=?0.64) in this general population sample. Principal Component Analyses, followed by parallel analyses and confirmatory factor analyses, identified four factors corresponding to distractibility/disinhibition, psychosis, increased libido and disrupted sleep. This factor structure remained stable across all assessment ages. Logistic regression analyses showed that the CBCL-MS had significantly higher predictive ability than both the other scales.ConclusionsOur data demonstrate that the CBCL-MS is a promising screening instrument for BD. The factor structure of the CBCL-MS showed remarkable temporal stability between late childhood and early adulthood suggesting that it maps on to meaningful developmental dimensions of liability to BD.
| S-EPMC3743889 | biostudies-literature
Project description:Introduction: Previous studies have primarily focused on the neuropathological mechanisms of the emotional circuit present in bipolar mania and bipolar depression. Recent studies applying resting-state functional magnetic resonance imaging (fMRI) have raise the possibility of examining brain-wide networks abnormality between the two oppositional emotion states, thus this study aimed to characterize the different functional architecture represented in mania and depression by employing group-independent component analysis (gICA). Materials and Methods: Forty-one bipolar depressive patients, 20 bipolar manic patients, and 40 healthy controls (HCs) were recruited and received resting-state fMRI scans. Group-independent component analysis was applied to the brain network functional connectivity analysis. Then, we calculated the correlation between the value of between-group differences and clinical variables. Results: Group-independent component analysis identified 15 components in all subjects, and ANOVA showed that functional connectivity (FC) differed significantly in the default mode network, central executive network, and frontoparietal network across the three groups. Further post-hoc t-tests showed a gradient descent of activity-depression > HC > mania-in all three networks, with the differences between depression and HCs, as well as between depression and mania, surviving after family wise error (FWE) correction. Moreover, central executive network and frontoparietal network activities were positively correlated with Hamilton depression rating scale (HAMD) scores and negatively correlated with Young manic rating scale (YMRS) scores. Conclusions: Three brain networks heighten activity in depression, but not mania; and the discrepancy regions mainly located in prefrontal, which may imply that the differences in cognition and emotion between the two states is associated with top-down regulation in task-independent networks.
| S-EPMC8032940 | biostudies-literature
Project description:In this study, we examined the point prevalence rate of atypical features in bipolar disorder, and estimated the potential impact of these features on treatment practices in China. Using the atypical features criteria of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), we documented the atypical symptoms in 3 906 consecutive participants with bipolar disorder enrolled at 26 psychiatric services across China. We further assessed the association between atypical features and the treatment approaches, including the prescription of antidepressants. The overall point prevalence rate of atypical features was 9.1% among patients with various bipolar disorder subtypes. When the definition was broadened to include atypical features B, the overall rate increased to 11.8%. Interestingly, among patients with the mixed state and remission subtypes, there was a significant difference in the rates of antidepressant medication usage between patients who met and those who did not meet the criteria for atypical features B. These findings indicate a trend of using antidepressants for these two types of patients with atypical features. Further, for both mixed state and remission patients, treatment approaches were related to atypical features B. Our findings provide evidence to assist clinicians to readily recognize atypical features in bipolar subtypes and can propose treatments based on these diagnoses.
| S-EPMC5562638 | biostudies-other