title: Individualized Prediction and Clinical Staging of Bipolar Disorders using Neuroanatomical Biomarkers.
abstract: BACKGROUND
  Neuroanatomical abnormalities in Bipolar disorder (BD) have previously been reported. However, the utility of these abnormalities in distinguishing individual BD patients from Healthy controls and stratify patients based on overall illness burden has not been investigated in a large cohort.
  
  
  METHODS
  In this study, we examined whether structural neuroimaging scans coupled with a machine learning algorithm are able to distinguish individual BD patients from Healthy controls in a large cohort of 256 subjects. Additionally, we investigated the relationship between machine learning predicted probability scores and subjects' clinical characteristics such as illness duration and clinical stages. Neuroimaging scans were acquired from 128 BD patients and 128 Healthy controls. Gray and white matter density maps were obtained and used to 'train' a relevance vector machine (RVM) learning algorithm which was used to distinguish individual patients from Healthy controls.
  
  
  RESULTS
  The RVM algorithm distinguished patients from Healthy controls with 70.3 % accuracy (74.2 % specificity, 66.4 % sensitivity, chi-square p<0.005) using white matter density data and 64.9 % accuracy (71.1 % specificity, 58.6 % sensitivity, chi-square p<0.005) with gray matter density. Multiple brain regions - largely covering the fronto - limbic system were identified as 'most relevant' in distinguishing both groups. Patients identified by the algorithm with high certainty (a high probability score) - belonged to a subgroup with more than ten total lifetime manic episodes including hospitalizations (late stage).
  
  
  CONCLUSIONS
  These results indicate the presence of widespread structural brain abnormalities in BD which are associated with higher illness burden - which points to neuroprogression.
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Benson
authors.initials: B
authors.lastname: Mwangi
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Mon-Ju
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Ives C
authors.initials: IC
authors.lastname: Passos
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Lavagnino
authors.affiliation: Department of Physical Medicine and Rehabilitation and TIRR Memorial Hermann Neuro-Recovery Research Center, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Keser
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Giovana B
authors.initials: GB
authors.lastname: Zunta-Soares
authors.affiliation: Department of Diagnostic and Interventional Radiology, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Khader M
authors.initials: KM
authors.lastname: Hasan
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil; Graduation Program in Psychiatry and Department of Psychiatry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: UT Center of Excellence on Mood Disorders, The University of Texas Health Science Center Houston, Houston, TX, USA.
authors.forename: Jair C
authors.initials: JC
authors.lastname: Soares
keywords: Bipolar Disorders; Clinical Staging; Machine Learning. Big Data; Manic Episodes; Neuroimaging