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Evaluation of children at risk for bipolar disorder: association between white matter analysis with diffusion tensor imaging and neuropsychological data

Grant number: 10/13155-4
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2011
Effective date (End): June 30, 2012
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Sheila Cavalcante Caetano
Grantee:Ana Maria Aristimunho Teixeira
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Up to 3% of adults are affected with Bipolar Disorder (BD) and the offspring of these patients constitute a population at risk for the development of psychiatric disorders. Magnetic resonance imaging (MRI) made possible the in vivo identification of anatomical, neurochemical and functional markers of BD; nevertheless, there is still a great deal of divergence in BD literature regarding structural and functional findings - especially in at risk population. This divergence could be explained by gray matter and functional abnormalities being caused by other, primary cause: abnormal connectivity, i.e., white matter (WM) alterations. Diffusion Tensor Imaging (DTI) is an MRI acquisition specific for the assessment of WM integrity and coherence. Preliminary data indicate that WM abnormalities may precede the disease onset and be present even in unaffected relatives - suggesting they could be further explored as an endophenotype for BD. Abnormal connectivity could also explain the cognitive deficits seen in BD patients. These deficits can be observed even in euthymic subjects and in their unaffected relatives - suggesting that these deficits could also be targeted as genetic vulnerability markers. Amongst the most important neuropsychological tests in BD research are Continuous Performance Test (CPT), a measure of sustained attention and inhibitory control; Wisconsin Card Sorting Test (WCST), designed to assess executive functions and mental flexibility; and Wechsler's Digit Span, that assesses verbal memory and attention. There has not been conducted any study associating cognitive performance and WM structural data in mood disorder patients so far. DTI combined with neuropsychological testing would help understand the causes of the cognitive deficits seen in BD and the evaluation of youth at risk would help clarify these deficits progression, increasing our knowledge of what is endophenotype, prodrome or scarring effect. Our hypothesis are that BD offspring, compared to healthy controls, will exhibit (i) reduced FA and/or increased diffusivity in frontolimbic regions and (ii) worse performance in neuropsychological tests when compared to healthy children of healthy parents. We also hypothesized that these abnormalities will be more pronounced in BD affected offspring of BD patients than non-affected BD offspring and that there will be an association between cognitive performance and FA/diffusivity values in BD offspring. Methods: We will recruit 60 subjects who will fulfill inclusion criteria: a) be between 6 and 18 years old; b) have one parent diagnosed with BD - of these, 30 will not have any psychiatric disorder and 30 will have BD. We will also recruit 30 healthy controls matched for gender, age and puberty degree with no history of psychiatric disorder in first-degree relatives. Psychiatric diagnosis will be established according to the DSM-IV criteria, using the Kiddie-SADS-PL interview and Structured Clinical Interview for DSM-IV. The MRI will be conducted at a 3.0 Tesla Philips scanner. Acquisition: the parameters are TR = 6106,0ms, TE = 65,0ms, FOV= 224x224mm, slice thickness = 2.0mm/no gap, matrix acquisition = 112x112 pixels, 3 averages, resulting in an isotropic voxel = 2,0x2,0x2,0 mm. Bioimage Suite will be utilized for image processing and SPM2 for VBM analysis of FA and diffusivity values. The association of FA and diffusivity values with cognitive performance will be given by Spearman's rank correlation coefficient. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TEIXEIRA, Ana Maria Aristimunho. Evaluation of white matter using diffusion tensor imaging in children at-risk and with bipolar disorder. 2012. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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