In spite of its high prevalence and clinical severity, the neurobiological basis of type II bipolar disorder (BD) is still relatively understudied. The study of the types I and II subtypes of BD would allow us to identify biological markers (endophenotypes) of diagnosis and treatment-response, besides improving our knowledge about the underlying pathophysiology of its clinical manifestations. We sought to study treatment-naïve patients with the types I and II subtypes of BD combining neuroimaging (structural MRI and diffusion tensor imaging), neurocognitive assessment, measurement of brain-derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF) levels in the serum, and expression and activity of the glycogen synthase kinase 3 ² (GSK3-²) enzyme in platelets. A group of healthy volunteers matched for age, gender and socioeconomic status will also be studied. A high-dimensional and multivariate classifier will be generated based on all obtained measures aiming to identify the pattern of neurobiological features that better separate the groups under study (i.e., BD type I, BD type II and controls). Measures of diagnostic performance will also be calculated (sensitivity, specificity, positive predictive value, negative predictive value and area under the ROC curve).
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