Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies

The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes) and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same

Moving black holes via singularity excision

We present a singularity excision algorithm appropriate for numerical simulations of black holes moving throughout the computational domain. The method is an extension of the excision procedure previously used to obtain stable simulations of single, non-moving black holes. The excision procedure also shares elements used in recent work to study the dynamics of a scalarfield in the background of a single, boosted black hole. The robustness of our excision method is tested with single black-hole evolutions using a coordinate system in which the coordinate location of the black hole, and thus the excision boundary, moves throughout the computational domain.Comment: 9 pages and 11 figure

The discrete energy method in numerical relativity: Towards long-term stability

The energy method can be used to identify well-posed initial boundary value problems for quasi-linear, symmetric hyperbolic partial differential equations with maximally dissipative boundary conditions. A similar analysis of the discrete system can be used to construct stable finite difference equations for these problems at the linear level. In this paper we apply these techniques to some test problems commonly used in numerical relativity and observe that while we obtain convergent schemes, fast growing modes, or ``artificial instabilities,'' contaminate the solution. We find that these growing modes can partially arise from the lack of a Leibnitz rule for discrete derivatives and discuss ways to limit this spurious growth.Comment: 18 pages, 22 figure

Mental Health Over Time in a Military Sample: The Impact of Alcohol Use Disorder on Trajectories of Psychopathology After Deployment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116086/1/jts22055.pd

Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry

Background and Objectives: There is no biomarker to predict lithium response. This study used CellPrint™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4+ lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). Materials and Methods: Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.6 mEq/L) for 16 weeks. Patients were assessed with standard rating scales and divided into two groups, responders (≥50% improvement from baseline) and non-responders. Twenty-eight intracellular proteins in CD4+ lymphocytes and monocytes were analyzed with CellPrint™, an enhanced flow cytometry procedure. Data were analyzed for differences in protein expression levels. Results: The intent-to-treat sample included 13 lithium-responders (12 blood samples before treatment and 9 after treatment) and 11 lithium-non-responders (11 blood samples before treatment and 4 after treatment). No significant differences in expression between the groups was observed prior to lithium treatment. After treatment, the majority of analytes increased expression in responders and decreased expression in non-responders. Significant increases were seen for PDEB4 and NR3C1 in responders. A significant decrease was seen for NR3C1 in non-responders. Conclusions: Lithium induced divergent directionality of protein expression depending on the whether the patient was a responder or non-responder, elucidating molecular characteristics of lithium responsiveness. A subsequent study with a larger sample size is warranted

Differences in intracellular protein levels in monocytes and CD4+ lymphocytes between bipolar depressed patients and healthy controls: A pilot study with tyramine-based signal-amplified flow cytometry

Highlights To measure 18 intracellular proteins in blood cells of bipolar depressed patients and healthy controls; TFour proteins in monocytes and 2 proteins in CD4+ T Cells were significantly lower in patients than in healthy controls; The studied proteins are involved in prolactin, leptin, BDNF, and interleukin-3 signal pathways; Studying intracellular proteins with enhanced flow cytometry may find biomarkers differentiating bipolar disorder from healthy controls. Abstract Background Molecular biomarkers for bipolar disorder (BD) that distinguish it from other manifestations of depressive symptoms remain unknown. The aim of this study was to determine if a very sensitive tyramine-based signal-amplification technology for flow cytometry (CellPrint™) could facilitate the identification of cell-specific analyte expression profiles of peripheral blood cells for bipolar depression (BPD) versus healthy controls (HCs). Methods The diagnosis of psychiatric disorders was ascertained with Mini International Neuropsychiatric Interview for DSM-5. Expression levels for eighteen protein analytes previously shown to be related to bipolar disorder were assessed with CellPrint™ in CD4+ T cells and monocytes of bipolar patients and HCs. Implementation of protein-protein interaction (PPI) network and pathway analysis was subsequently used to identify new analytes and pathways for subsequent interrogations. Results Fourteen drug-naïve or -free patients with bipolar I or II depression and 17 healthy controls (HCs) were enrolled. The most distinguishable changes in analyte expression based on t-tests included GSK3β, HMGB1, IRS2, phospho-GSK3αβ, phospho-RELA, and TSPO in CD4+ T cells and calmodulin, GSK3β, IRS2, and phospho-HS1 in monocytes. Subsequent PPI and pathway analysis indicated that prolactin, leptin, BDNF, and interleukin-3 signal pathways were significantly different between bipolar patients and HCs. Limitation The sample size of the study was small and 2 patients were on medications. Conclusion In this pilot study, CellPrint™ was able to detect differences in cell-specific protein levels between BPD patients and HCs. A subsequent study including samples from patients with BPD, major depressive disorder, and HCs is warranted

Subthreshold PTSD and PTSD in a prospective‐longitudinal cohort of military personnel: Potential targets for preventive interventions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146501/1/da22819_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146501/2/da22819.pd

Precision Epoch of Reionization studies with next-generation CMB experiments

Future arcminute resolution polarization data from ground-based Cosmic Microwave Background (CMB) observations can be used to estimate the contribution to the temperature power spectrum from the primary anisotropies and to uncover the signature of reionization near $\ell=1500$ in the small angular-scale temperature measurements. Our projections are based on combining expected small-scale E-mode polarization measurements from Advanced ACTPol in the range $300<\ell<3000$ with simulated temperature data from the full Planck mission in the low and intermediate $\ell$ region, $2<\ell<2000$. We show that the six basic cosmological parameters determined from this combination of data will predict the underlying primordial temperature spectrum at high multipoles to better than $1\%$ accuracy. Assuming an efficient cleaning from multi-frequency channels of most foregrounds in the temperature data, we investigate the sensitivity to the only residual secondary component, the kinematic Sunyaev-Zel'dovich (kSZ) term. The CMB polarization is used to break degeneracies between primordial and secondary terms present in temperature and, in effect, to remove from the temperature data all but the residual kSZ term. We estimate a $15 \sigma$ detection of the diffuse homogeneous kSZ signal from expected AdvACT temperature data at $\ell>1500$, leading to a measurement of the amplitude of matter density fluctuations, $\sigma_8$, at $1\%$ precision. Alternatively, by exploring the reionization signal encoded in the patchy kSZ measurements, we bound the time and duration of the reionization with $\sigma(z_{\rm re})=1.1$ and $\sigma(\Delta z_{\rm re})=0.2$. We find that these constraints degrade rapidly with large beam sizes, which highlights the importance of arcminute-scale resolution for future CMB surveys.Comment: 10 pages, 10 figure

Investigating the structural compaction of biomolecules upon transition to the gas-phase using ESI-TWIMS-MS

Collision cross-section (CCS) measurements obtained from ion mobility spectrometry-mass spectrometry (IMS-MS) analyses often provide useful information concerning a protein’s size and shape and can be complemented by modeling procedures. However, there have been some concerns about the extent to which certain proteins maintain a native-like conformation during the gas-phase analysis, especially proteins with dynamic or extended regions. Here we have measured the CCSs of a range of biomolecules including non-globular proteins and RNAs of different sequence, size, and stability. Using traveling wave IMS-MS, we show that for the proteins studied, the measured CCS deviates significantly from predicted CCS values based upon currently available structures. The results presented indicate that these proteins collapse to different extents varying on their elongated structures upon transition into the gas-phase. Comparing two RNAs of similar mass but different solution structures, we show that these biomolecules may also be susceptible to gas-phase compaction. Together, the results suggest that caution is needed when predicting structural models based on CCS data for RNAs as well as proteins with non-globular folds