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Balasubramaniam M.,Duke University | Telles S.,Indian Council of Medical Research Center for Advanced Research | Doraiswamy P.M.,Duke University | Doraiswamy P.M.,Duke Institute for Brain science
Frontiers in Psychiatry | Year: 2013

Background: The demand for clinically efficacious, safe, patient acceptable, and cost-effective forms of treatment for mental illness is growing. Several studies have demonstrated benefit from yoga in specific psychiatric symptoms and a general sense of well-being. Objective: To systematically examine the evidence for efficacy of yoga in the treatment of selected major psychiatric disorders. Methods: Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases, MEDLINE, EMBASE, and PsycINFO, were performed through April 2011 and an updated in June 2011 using the keywords yoga AND psychiatry OR depression OR anxiety OR schizophrenia OR cognition OR memory OR attention AND randomized controlled trial (RCT). Studies with yoga as the independent variable and one of the above mentioned terms as the dependent variable were included and exclusion criteria were applied. Results:The search yielded a total of 124 trials, of which 16 met rigorous criteria for the final review. Grade B evidence supporting a potential acute benefit for yoga exists in depression (four RCTs), as an adjunct to pharmacotherapy in schizophrenia (three RCTs), in children with ADHD (two RCTs), and Grade C evidence in sleep complaints (three RCTs). RCTs in cognitive disorders and eating disorders yielded conflicting results. No studies looked at primary prevention, relapse prevention, or comparative effectiveness versus pharmacotherapy. Conclusion:There is emerging evidence from randomized trials to support popular beliefs about yoga for depression, sleep disorders, and as an augmentation therapy. Limitations of literature include inability to do double-blind studies, multiplicity of comparisons within small studies, and lack of replication. Biomarker and neuroimaging studies, those comparing yoga with standard pharmaco and psychotherapies, and studies of long-term efficacy are needed to fully translate the promise of yoga for enhancing mental health. © 2013 Balasubramaniam, Telles and Doraiswamy.

Li Q.,Duke University | Ha T.S.,University of Texas Southwestern Medical Center | Okuwa S.,Duke University | Wang Y.,Duke University | And 5 more authors.
Current Biology | Year: 2013

Background Sensory neuron diversity ensures optimal detection of the external world and is a hallmark of sensory systems. An extreme example is the olfactory system, as individual olfactory receptor neurons (ORNs) adopt unique sensory identities by typically expressing a single receptor gene from a large genomic repertoire. In Drosophila, about 50 different ORN classes are generated from a field of precursor cells, giving rise to spatially restricted and distinct clusters of ORNs on the olfactory appendages. Developmental strategies spawning ORN diversity from an initially homogeneous population of precursors are largely unknown. Results Here we unravel the nested and binary logic of the combinatorial code that patterns the decision landscape of precursor states underlying ORN diversity in the Drosophila olfactory system. The transcription factor Rotund (Rn) is a critical component of this code that is expressed in a subset of ORN precursors. Addition of Rn to preexisting transcription factors that assign zonal identities to precursors on the antenna subdivides each zone and almost exponentially increases ORN diversity by branching off novel precursor fates from default ones within each zone. In rn mutants, rn-positive ORN classes are converted to rn-negative ones in a zone-specific manner. Conclusions We provide a model describing how nested and binary changes in combinations of transcription factors could coordinate and pattern a large number of distinct precursor identities within a population to modulate the level of ORN diversity during development and evolution. © 2013 Elsevier Ltd.

Boyd J.L.,Duke University | Skove S.L.,Duke University | Rouanet J.P.,Duke University | Pilaz L.-J.,Duke University | And 5 more authors.
Current Biology | Year: 2015

The human neocortex differs from that of other great apes in several notable regards, including altered cell cycle, prolonged corticogenesis, and increased size [1-5]. Although these evolutionary changes most likely contributed to the origin of distinctively human cognitive faculties, their genetic basis remains almost entirely unknown. Highly conserved non-coding regions showing rapid sequence changes along the human lineage are candidate loci for the development and evolution of uniquely human traits. Several studies have identified human-accelerated enhancers [6-14], but none have linked an expression difference to a specific organismal trait. Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]. Using transgenic mice, we demonstrate dramatic differences in human and chimpanzee HARE5 activity, with human HARE5 driving early and robust expression at the onset of corticogenesis. Similar to HARE5 activity, FZD8 is expressed in neural progenitors of the developing neocortex [17-19]. Chromosome conformation capture assays reveal that HARE5 physically and specifically contacts the core Fzd8 promoter in the mouse embryonic neocortex. To assess the phenotypic consequences of HARE5 activity, we generated transgenic mice in which Fzd8 expression is under control of orthologous enhancers (Pt-HARE5::Fzd8 and Hs-HARE5::Fzd8). In comparison to Pt-HARE5::Fzd8, Hs-HARE5::Fzd8 mice showed marked acceleration of neural progenitor cell cycle and increased brain size. Changes in HARE5 function unique to humans thus alter the cell-cycle dynamics of a critical population of stem cells during corticogenesis and may underlie some distinctive anatomical features of the human brain. © 2015 Elsevier Ltd All rights reserved.

Peterson D.E.,Duke University | Chen S.D.,Duke University | Calabrese E.,Duke University | White L.E.,Duke University | And 2 more authors.
Neuroradiology Journal | Year: 2016

The goal of this study was to apply image registration-based automated segmentation methods to measure diffusion tensor imaging (DTI) metrics within the canine brain. Specifically, we hypothesized that this method could measure DTI metrics within the canine brain with greater reproducibility than with hand-drawn region of interest (ROI) methods. We performed high-resolution post-mortem DTI imaging on two canine brains on a 7 T MR scanner. We designated the two brains as brain 1 and brain 2. We measured DTI metrics within the corpus callosum of brain 1 using a hand-drawn ROI method and an automated segmentation method in which ROIs from brain 2 were transformed into the space of brain 1. We repeated both methods in order to measure their reliability. Mean differences between the two sets of hand-drawn ROIs ranged from 4% to 10%. Mean differences between the handdrawn ROIs and the automated ROIs were less than 3%. The mean differences between the first and second automated ROIs were all less than 0.25%. Our findings indicate that the image registration-based automated segmentation method was clearly the more reproducible method. These results provide the groundwork for using image registration-based automated segmentation methods to measure DTI metrics within the canine brain. Such methods will facilitate the study of white matter pathology in canine models of neurologic disease. © The Author(s) 2015.

Zannas A.S.,Duke University | Okuno Y.,Kyoto University | Doraiswamy P.M.,Duke University | Doraiswamy P.M.,Duke Institute for Brain science
Pharmacotherapy | Year: 2014

Study Objectives: Case reports suggest a relationship between cholinesterase inhibitors (ChEIs) and Pisa syndrome (PS), also known as pleurothotonus, a form of dystonia, but this relationship has not been systematically examined. Our objective was to estimate the adjusted reporting ratios of PS with donepezil, rivastigmine, and galantamine in the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. DESIGN: Retrospective analysis of adverse event reports in the FAERS database. PATIENTS: Patients with drug-related adverse events in the FAERS database. MEASUREMENTS AND MAIN RESULTS: The Gamma Poisson Shrinker algorithm was used to estimate the empirical Bayes geometric mean (EBGM) along with the lower and upper 90% confidence interval (CI) limits (EB05 and EB95, respectively), as measures of the adjusted reporting ratio of PS in patients taking ChEIs. EB05 < 2.0 was used as the cutoff for significance for the signals. The EBGM (EB05) was 37.9 (30) for all ChEIs, 25.6 (17.6) for donepezil, 76.4 (50.3) for galantamine, and 33.7 (21.2) for rivastigmine. All adverse event signals were strongly significant based on the a priori set EB05 cutoff. The female:male ratio in the reported cases was 2:1. No significant signals were found between ChEIs and other dystonias. About half of the ChEI users were also taking concomitant antipsychotics. CONCLUSION: Although FAERS data cannot establish causality due to reporting biases, our findings support a potential dopaminergic-cholinergic imbalance as an underlying mechanism for PS and may help increase clinician awareness, early identification, and treatment of ChEI-related dystonias. KEY WORDS cholinesterase inhibitors, dystonia, Pisa syndrome, pleurothotonus. © 2013 Pharmacotherapy Publications, Inc.

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