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Bipolar disorder (BD) is a severe illness with a lifetime morbid risk of approximately 4%. Clinical studies described obesity in over 60% of BD patients. It has been reported in adolescent, early onset and drug naive patients, although it may increase after diagnosis and treatment. It worsens the severity of illness, influences cognition and functional outcomes. But the neurobiological mechanisms underlying the relationship between obesity and BD illness are still unknown. Changes of white matter (WM) microstructure are one of the most consistently reported findings in neuroimaging studies of BD and have been proposed as structural biomarker. These changes can be studied in vivo, in a non-invasive manner though Diffusion tensor imaging (DTI). The aim of this study is to investigate if Body Mass Index (BMI) could correlate with WM integrity in a sample of depressed bipolar patients. Methods: We evaluated BMI in a sample of 140 depressed patients affected by Bipolar Disorder and 97 Healthy Controls. Blood samples were then drawn for all patients and processed for analysis of serum lipid levels of total cholesterol, glucose and triglycerides. Voxelwise DTI analyses were performed using Tract-Based Spatial Statistics. BMI was negatively associated with fractional anisotropy and positively correlated with mean, axial and radial diffusivity. The effects were spread in large portions of the WM skeleton, and detected for the different DTI measures in large overlapping networks of WM fibers, with signal peaks in anterior corona radiata, anterior thalamic radiation, inferior fronto-occipital fasciculus and corpus callosum. Same fiber tracts were found to be involved when serum cholesterol, triglycerides and glucose levels have been considered. These last correlation analysis were performed on BD only, since no significant results emerged in healthy population between BMI and DTI measures. We observed that a higher BMI is associated with DTI measures in WM fiber tracts crucial to mood regulation, increased food seeking and neurocognitive functioning, leading us to support the association between obesity and worse severity of illness and cognitive impairment. Several mechanisms underlying this relationship have been proposed, such as increased levels of pro-inflammatory cytokines, impaired glucose metabolism, lipid peroxidation that have been reported in BD and have been associated with WM loss and altered GM volume. BMI might contribute to the pathophysiology of BD through a detrimental action on structural connectivity in critical cortico-limbic networks. Moreover, the high levels of significance of the effects of more precise markers of metabolism, such as serum lipids and glucose, on DTI measures suggest that the significance of the effect of BMI on WM might be driven by the same metabolic processes that regulate the blood peripheral levels of these substances.

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This page is a summary of: Body mass index associates with white matter microstructure in bipolar depression, Bipolar Disorders, March 2017, Wiley,
DOI: 10.1111/bdi.12484.
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