Ottawa Health Research Institute

Bells Corners, Canada

Ottawa Health Research Institute

Bells Corners, Canada

The Ottawa Hospital Research Institute , formerly Ottawa Health Research Institute, is a non-profit academic health research institute located in the city of Ottawa. It was formed in 2001 following the merger of three Ottawa hospitals. The Ottawa Hospital Research Institute is the research arm of The Ottawa Hospital and affiliated with the University of Ottawa.As of April 2013, the Ottawa Hospital Research Institute houses approximately 560 scientists and clinical investigators, 475 students and research fellows, and 700 support staff. It has five research programs: Cancer Therapeutics; Chronic Disease; Clinical Epidemiology; Regenerative Medicine; and Neuroscience.Ronald G. Worton was the research institute's founding CEO and Scientific Director in 2001. In 2007, Duncan Stewart, formerly Chief Cardiologist of St. Michael's Hospital in Toronto and Director of Cardiology of University of Toronto, took over as CEO and Scientific Director. Wikipedia.

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Hamon M.,French Institute of Health and Medical Research | Blier P.,Ottawa Health Research Institute
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2013

Extensive studies showed that monoaminergic neurotransmission that involves serotonin (5-HT), norepinephrine (NE) and dopamine (DA) exerts major influence on brain circuits concerned by the regulation of mood, reactivity to psychological stress, self-control, motivation, drive, and cognitive performance. Antidepressants targeting monoamines directly affect the functional tone of these circuits, notably in limbic and frontocortical areas, and evidence has been provided that this action plays a key role in their therapeutic efficacy. Indeed, at least some of functional changes detected by functional magnetic resonance imaging in emotion- and cognitive-related circuits such as the one involving limbic-cortical-striatal-pallidal-thalamic connections in depressed patients can be reversed by monoamine-targeted antidepressants. However, antidepressants acting selectively on only one monoamine, such as selective inhibitors of 5-HT or NE reuptake, alleviate depression symptoms in a limited percentage of patients, and are poorly effective to prevent recurrence. Thorough investigations for the last 30years allowed the demonstration of the existence of functional interactions between 5-HT, NE and DA systems, and the identification of the specific receptors involved. In particular, 5-HT systems were shown to exert negative influence on NE and DA systems through 5-HT2A and 5-HT2C receptor- mediated mechanisms, respectively. On the other hand, complex positive and negative influences of NE system on 5-HT neurotransmission are mediated through α[U+F061]1- and α[U+F061]2-adrenergic receptors, respectively. These data provided a rationale for the design of new, multimodal, therapeutic strategies involving drugs acting not only at the "historical" targets such as the 5-HT and/or the NE transporter, but also at other molecular targets to improve their efficacy and their tolerability. © 2013 Elsevier Inc.

Northoff G.,Ottawa Health Research Institute
Current Opinion in Neurobiology | Year: 2013

Depression, conceptualized as major depressive disorder (MDD), is a complex psychiatric disorder with multiple behavioral changes and alterations in various brain regions. Biochemically, serotonin and others substances like GABA, glutamate, norepinephrin, adrenaline/noradrenaline play an essential role in the pathogenesis of MDD. The paper reviews recent human neuroimaging findings on how the genes underlying these biochemical substances modulate neural activity, behavior, and ultimately clinical symptoms. Current data provide solid evidence that genes related to serotonin impact emotion-related neural activity in the amygdala and the anterior cingulate cortex. By contrast, evidence is not as strong for genes related to biochemical substances other than serotonin and other regions of the brain. The review concludes with discussing future genetic, neural, and clinical challenges that point out the central role of gene. × environment and brain. × environment interactions as genetic and neural predispositions of depression. © 2012 Elsevier Ltd.

Qin P.,Ottawa Health Research Institute | Northoff G.,University of Ottawa
NeuroImage | Year: 2011

The problem of the self has been of increasing interest in recent neuroscience. Brain imaging studies have raised the question of whether neural activity in cortical midline regions is self-specific and whether self-specific activity is related to resting state activity (RSA). A quantitative meta-analysis that included 87 studies, representing 1433 participants, was conducted to discuss these questions. First, the specificity of the self (e.g. hearing one's own name, seeing one's own face) was tested and compared across familiar (using stimuli from personally known people) and other (non-self-non-familiar, i.e. strangers and widely-known figures) conditions. Second, the relationship between the self and resting state activity, as reflected by the default-mode network (DMN), was tested. The results indicated that the perigenual anterior cingulate cortex (PACC) is specifically involved in self-processing when compared to familiarity, other, and task/stimulus effects. On the contrary, other midline regions, i.e., medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) were functionally unspecific as they were recruited during the processing of both self-specific and familiar stimuli. Finally, the PACC was recruited during self-specific stimuli and this activity overlapped with DMN activity during resting state, thus distinguishing the self-related processing from both that of the familiar and other conditions. Taken together, our data suggest that our sense of self may result from a specific kind of interaction between resting state activity and stimulus-induced activity, i.e., rest-stimulus interaction, within the midline regions. © 2011 Elsevier Inc.

Northoff G.,Ottawa Health Research Institute | Hayes D.J.,Ottawa Health Research Institute
Biological Psychiatry | Year: 2011

Neuroscience has increasingly explored the neural mechanisms underlying our sense of self. Recent studies have demonstrated the recruitment of regions like the ventral tegmental area, ventromedial prefrontal cortex, and the ventral striatum to self-specific stimuliregions typically associated with reward-related processing. This raises the question of whether there is a relationship between self and reward and, if so, how these different fields can be linked. Three relationship models that aim to explore the relationship between self and reward are discussed here: integration, segregation, and parallel processing. Their pros and cons are reviewed in light of the most recent findings. The conclusion is that both the fields of self and reward may benefit from increased interaction. This interaction may help to fill in some of the missing pieces regarding reward-related processing, as well as illuminate how brain function can bring forward the philosophical concept and psychological reality of self. © 2011 Society of Biological Psychiatry.

Health administrative data is increasingly being used for chronic disease surveillance. This study explored agreement between administrative and survey data for ascertainment of seven key chronic diseases, using individually linked data from a large population of individuals in Ontario, Canada. All adults who completed any one of three cycles of the Canadian Community Health Survey (2001, 2003 or 2005) and agreed to have their responses linked to provincial health administrative data were included. The sample population included 85,549 persons. Previously validated case definitions for myocardial infarction, asthma, diabetes, chronic lung disease, stroke, hypertension and congestive heart failure based on hospital and physician billing codes were used to identify cases in health administrative data and these were compared with self-report of each disease from the survey. Concordance was measured using the Kappa statistic, percent positive and negative agreement and prevalence estimates. Agreement using the Kappa statistic was good or very good (kappa range: 0.66-0.80) for diabetes and hypertension, moderate for myocardial infarction and asthma and poor or fair (kappa range: 0.29-0.36) for stroke, congestive heart failure and COPD. Prevalence was higher in health administrative data for all diseases except stroke and myocardial infarction. Health Utilities Index scores were higher for cases identified by health administrative data compared with self-reported data for some chronic diseases (acute myocardial infarction, stroke, heart failure), suggesting that administrative data may pick up less severe cases. In the general population, discordance between self-report and administrative data was large for many chronic diseases, particularly disease with low prevalence, and differences were not easily explained by individual and disease characteristics.

Hasler G.,University of Bern | Northoff G.,Ottawa Health Research Institute
Molecular Psychiatry | Year: 2011

Psychiatry research lacks an in-depth understanding of mood disorders phenotypes, leading to limited success of genetics studies of major depressive disorder (MDD). The dramatic progress in safe and affordable magnetic resonance-based imaging methods has the potential to identify subtle abnormalities of neural structures, connectivity and function in mood disordered subjects. This review paper presents strategies to improve the phenotypic definition of MDD by proposing imaging endophenotypes derived from magnetic resonance spectroscopy measures, such as cortical gamma-amino butyric acid (GABA) and glutamate/glutamine concentrations, and from measures of resting-state activity and functional connectivity. The proposed endophenotypes are discussed regarding specificity, mood state-independence, heritability, familiarity, clinical relevance and possible associations with candidate genes. By improving phenotypic definitions, the discovery of new imaging endophenotypes will increase the power of candidate gene and genome-wide associations studies. It will also help to develop and evaluate novel therapeutic treatments and enable clinicians to apply individually tailored therapeutic approaches. Finally, improvements of the phenotypic definition of MDD based on neuroimaging measures will contribute to a new classification system of mood disorders based on etiology and pathophysiology. © 2011 Macmillan Publishers Limited All rights reserved.

Bentzinger C.F.,Ottawa Health Research Institute
Cold Spring Harbor perspectives in biology | Year: 2012

The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.

Blier P.,Ottawa Health Research Institute
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent.

Blier P.,Ottawa Health Research Institute
Journal of Clinical Psychiatry | Year: 2013

Residual symptoms are a common hindrance to daily life for patients with major depressive disorder. Even after antidepressant treatment has led patients to meet remission criteria, almost all patients have at least 1 symptom that remains unresolved. These symptoms can increase the risk for relapse, a chronic course, and suicide attempts. Residual symptoms are lingering symptoms that do not resolve with treatment of the depressive episode, and they should be distinguished from symptoms of comorbid psychiatric or medical conditions and medication side effects. By understanding how various antidepressants affect the 3 monoamine systems of serotonin, norepinephrine, and dopamine, clinicians can select treatments based on the most effective mechanism of action. Dual-action agents show promise for alleviating depressive symptoms that do not resolve with single-action agents. Medications that increase norepinephrine or dopamine neurotransmission may improve several common residual symptoms left after treatment with serotonin-specific agents. Treatment strategies like adjunctive therapies and dosing options are given for common residual symptoms, including sleep difficulties, sexual dysfunction, and pain. For patients to truly regain their quality of life, clinicians must target residual symptoms. © Copyright 2013 Physicians Postgraduate Press, Inc.

Ottawa Health Research Institute | Date: 2014-02-14

The present invention provides novel stem cells, nucleotide sequences and proteins therefrom. More specifically, the present invention provides Pax7+/Myf5 stem cells and methods for identifying and isolating them. Also provided is a MEGF10 nucleotide sequence and protein.

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