title: Volume and asymmetry abnormalities of insula in antipsychotic-naive schizophrenia: a 3-tesla magnetic resonance imaging study.
abstract: BACKGROUND
  Insula, which is a vital brain region for self-awareness, empathy, and sensory stimuli processing, is critically implicated in schizophrenia pathogenesis. Existing studies on insula volume abnormalities report inconsistent findings potentially due to the evaluation of 'antipsychotic-treated' schizophrenia patients as well as suboptimal methodology.
  
  
  OBJECTIVE
  To understand the role of insula in schizophrenia.
  
  
  METHODS
  In this first-time 3-T magnetic resonance imaging study, we examined antipsychotic-naive schizophrenic patients (N=30) and age-, sex-, handedness- and education-matched healthy controls (N=28). Positive and negative symptoms were scored with good interrater reliability (intraclass correlation coefficient (ICC)>0.9) by using the scales for negative and positive symptoms. Gray matter volume of insula and its anterior/posterior subregions were measured by using a three-dimensional, interactive, semiautomated software based on the valid method with good interrater reliability (ICC>0.85). Intracranial volume was automatically measured by using the FreeSurfer software.
  
  
  RESULTS
  Patients had significantly deficient gray matter volumes of left (F=33.4; P<0.00001) and right (F=11.9; P=0.001) insula after controlling for the effects of age, sex, and intracranial volume. Patients with predominantly negative symptoms had a significantly deficient right posterior insula volume than those with predominantly positive symptoms (F=6.3; P=0.02). Asymmetry index analysis revealed anterior insular asymmetry to be significantly reversed (right>left) in male patients in comparison with male controls (left>right) (t=2.7; P=0.01).
  
  
  CONCLUSIONS
  Robust insular volume deficits in antipsychotic-naive schizophrenia support intrinsic role for insula in pathogenesis of this disorder. The first-time demonstration of a relationship between right posterior insular deficit and negative symptoms is in tune with the background neurobiological literature. Another novel observation of sex-specific anterior insular asymmetry reversal in patients supports evolutionary postulates of schizophrenia pathogenesis.
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Harve Shanmugam
authors.initials: HS
authors.lastname: Virupaksha
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Kalmady
authors.forename: Venkataram
authors.initials: V
authors.lastname: Shivakumar
authors.forename: Rashmi
authors.initials: R
authors.lastname: Arasappa
authors.forename: Ganesan
authors.initials: G
authors.lastname: Venkatasubramanian
authors.forename: Bangalore N
authors.initials: BN
authors.lastname: Gangadhar