| Grant number: | 09/14891-9 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | September 01, 2010 |
| End date: | August 31, 2013 |
| Field of knowledge: | Health Sciences - Medicine - Psychiatry |
| Principal Investigator: | Rodrigo Machado-Vieira |
| Grantee: | Rodrigo Machado-Vieira |
| Host Institution: | Instituto de Psiquiatria Doutor Antonio Carlos Pacheco e Silva (IPq). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
| Associated researchers: | Claudia da Costa Leite ; Geraldo Busatto Filho ; Leda Leme Talib ; Maria Concepción García Otaduy ; Wagner Farid Gattaz |
| Associated scholarship(s): | 10/16643-0 - A longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant, BP.JP |
Abstract
Mood disorders are the most prevalent psychiatric, presenting chronic course and high morbidity, affecting 10-15% of population. Diverse structural, functional and biochemical cerebral changes described in the pathophysiology of mood disorders, in special Bipolar Disorder (BPD), have been associated with impairments in neuroprotective mechanisms and cellular resilience leading to cellular stress and atrophy. Altered levels of markers associated with neuronal viability in functional imaging studies, as well as dysfunctions in the mitochondrial and endoplasmic reticulum activity and neurotrophins levels have been consistently associated with these deleterious cellular effects. However, the clinical relevance of these pathophysiological findings have been rarely addressed. Meanwhile, lithium has been considered the most used mood stabilizer worldwide, showing significant efficacy in the treatment of manic and depressive episodes, as well as in the prevention of suicide and maintenance. Several studies have demonstrated significant neuroprotective and neurotrophic effects induced by lithium treatment in diverse cellular and molecular targets, but again, few is known about the potential association between these cerebral effects and the its therapeutic clinical efficacy induced by this proof of concept agent. The present project aims to investigate brain levels of lithium using magnetic resonance spectroscopy (7Li-MRS) and its association with different markers of neuronal viability such as n-acetyl-aspartate (using 1H-MRS), as well as peripheral markers of mitochodrial, endoplasmic reticulum and neurotrophic factors activity, all highly implicated in the pathophysiology of BD. Thirty subjects with a DSM-ID-TR diagnosis of BPD during a depressive or hypomanic episode will be divided in two groups according to age and time of illness. All patients will receive lithium (flexible therapeutic dose) for 6 weeks and improvement will be evaluated weekly using depression and mania rating scales; this study also objectives to identify state/trait markers and predictors of response. The investigator has been working in this area in the last ten years, in which the last three and a half in the Lab of Molecular Pathophysiology and Experimental Therapeutics, NIMH, NIH. The candidate is looking forward to establish appropriate structure to develop a "Research Center for the Study of Neuroplasticity and Neuroprotection in Psychiatric Disorders" in the Institute of Psychiatry, University of Sao Paulo, Brazil. Overall, the study on the neuroplasticity-mediated pathophysiological basis of BPD implicated in the clinical presentation and outcome may shed light on the development of new, improved therapeutics for this and other devastating psychiatric disorders. (AU)
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