Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions

Dynamically Driven Renormalization Group Applied to Sandpile Models

The general framework for the renormalization group analysis of self-organized critical sandpile models is formulated. The usual real space renormalization scheme for lattice models when applied to nonequilibrium dynamical models must be supplemented by feedback relations coming from the stationarity conditions. On the basis of these ideas the Dynamically Driven Renormalization Group is applied to describe the boundary and bulk critical behavior of sandpile models. A detailed description of the branching nature of sandpile avalanches is given in terms of the generating functions of the underlying branching process.Comment: 18 RevTeX pages, 5 figure

Personality disorder among youth with first episode psychotic mania: An important target for specific treatment?

Personality disorder is a common co-occurrence ('comorbidity') among patients with bipolar disorder and appears to affect outcome negatively. However, there is little knowledge about the impact of this comorbidity in the early phases of bipolar disorder. We examined the prevalence and effect of personality disorder co-occurrence on outcome in a cohort of youth with first episode mania with psychotic features. Seventy-one first episode mania patients, aged 15-29, were assessed at baseline, 6, 12, and 18 months as part of a randomized controlled trial of olanzapine and chlorpromazine as add-on to lithium in first episode mania with psychotic features. The current study involved secondary analysis of trial data. A co-occurring clinical personality disorder diagnosis was present in 16.9% of patients. Antisocial and narcissistic personality disorders were the most common diagnoses. Patients with co-occurring personality disorder had higher rates of readmission to hospital, lower rates of symptomatic recovery and poorer functional levels at 6 months, but these differences disappeared after 12 and 18 months. In the early phase of bipolar disorder, patients with personality disorder comorbidity display delayed symptomatic and functional recovery and increased likelihood to need hospital readmissions. These observations suggest that routine assessment for personality disorder and specific interventions are important in order to improve short-term treatment efficacy in this subgroup

Comments on Non-Commutative Phenomenology

It is natural to ask whether non-commutative geometry plays a role in four dimensional physics. By performing explicit computations in various toy models, we show that quantum effects lead to violations of Lorentz invariance at the level of operators of dimension three or four. The resulting constraints are very stringent.Comment: Correction of an error in the U(1) and U(N) calculation leads to stronger limits than those given previously Clarifying comments and reference adde

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

High Preservation of CpG Cytosine Methylation Patterns at Imprinted Gene Loci in Liver and Brain of Aged Mice

A gradual loss of the correct patterning of 5-methyl cytosine marks in gene promoter regions has been implicated in aging and age-related diseases, most notably cancer. While a number of studies have examined DNA methylation in aging, there is no consensus on the magnitude of the effects, particularly at imprinted loci. Imprinted genes are likely candidate to undergo age-related changes because of their demonstrated plasticity in utero, for example, in response to environmental cues. Here we quantitatively analyzed a total of 100 individual CpG sites in promoter regions of 11 imprinted and non-imprinted genes in liver and cerebral cortex of young and old mice using mass spectrometry. The results indicate a remarkably high preservation of methylation marks during the aging process in both organs. To test if increased genotoxic stress associated with premature aging would destabilize DNA methylation we analyzed two DNA repair defective mouse models showing a host of premature aging symptoms in liver and brain. However, also in these animals, at the end of their life span, we found a similarly high preservation of DNA methylation marks. We conclude that patterns of DNA methylation in gene promoters of imprinted genes are surprisingly stable over time in normal, postmitotic tissues and that the

Hadronic Parity Violation and Inelastic Electron-Deuteron Scattering

We compute contributions to the parity-violating (PV) inelastic electron-deuteron scattering asymmetry arising from hadronic PV. While hadronic PV effects can be relatively important in PV threshold electro- disintegration, we find that they are highly suppressed at quasielastic kinematics. The interpretation of the PV quasielastic asymmetry is, thus, largely unaffected by hadronic PV.Comment: 27 pages, 13 figures, uses REVTeX and BibTe

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.