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Evidence for the continuous latent structure of mania and depression in out-patients with bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

ABSTRACT: 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.

SUBMITTER: Prisciandaro JJ

PROVIDER: S-EPMC4751879 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Evidence for the continuous latent structure of mania and depression in out-patients with bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Prisciandaro J J JJ Tolliver B K BK

Psychological medicine 20150417 12

<h4>Background</h4>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 sympt ...[more]

PMID: 25881582

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Project description:BackgroundMany patients with bipolar disorder receive multi-drug treatment regimens, but the distinguishing profiles of patients who receive complex pharmacologies have not been established.MethodPrescribing patterns of lithium, anticonvulsants, antidepressants, and antipsychotics were examined for 4,035 subjects with bipolar disorder (DSM-IV) immediately prior to entering the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Subjects were recruited for participation across 22 centers in the United States between November 1999 and July 2005. The quality receiver operating characteristic (ROC) method was used to develop composite profiles of patients receiving complex regimens (p < .01 for all iterations).ResultsUse of 3 or more medications occurred in 40% of subjects, while 18% received 4 or more agents. Quality ROC analyses revealed that subjects had a 64% risk for receiving a complex regimen (> or = 4 medications) if they had (1) ever taken an atypical antipsychotic, (2) > or = 6 lifetime depressive episodes, (3) attempted suicide, and (4) an annual income > or = $75,000. Complex polypharmacy was least often associated with lithium, divalproex, or carbamazepine and most often associated with atypical antipsychotics or antidepressants. Contrary to expectations, a history of psychosis, age at onset, bipolar I versus II subtype, history of rapid cycling, prior hospitalizations, current illness state, and history of alcohol or substance use disorders did not significantly alter the risk profiles for receiving complex regimens.ConclusionComplex polypharmacy involving at least 4 medications occurs in approximately 1 in 5 individuals with bipolar disorder. Use of traditional mood stabilizers is associated with fewer cotherapies. Complex regimens are especially common in patients with substantial depressive illness burden and suicidality, for whom simpler drug regimens may fail to produce acceptable levels of response.Trial registrationclinicaltrials.gov Identifier: NCT00012558.

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.

Dataset Information

Evidence for the continuous latent structure of mania and depression in out-patients with bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Publications

Evidence for the continuous latent structure of mania and depression in out-patients with bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Similar Datasets

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