title: At the boundary of the self: the insular cortex in patients with childhood-onset schizophrenia, their healthy siblings, and normal volunteers.
abstract: The insular cortex (insula), whose normal function involves delineating the boundary between self and non-self stimuli, has been implicated in the pathophysiology of the positive symptoms of schizophrenia, including hallucinations and delusions. Childhood-onset schizophrenia (COS), that includes the onset of psychosis before age 13, is a severe and continuous form of the illness which shows profound and global progressive cortical brain abnormalities during adolescence which merge in the adult pattern with age. Using prospectively acquired anatomic brain magnetic resonance imaging (MRI) scans, a matched sample of COS patients, their nonpsychotic full siblings and healthy volunteers, we measured insular volume using the FreeSurfer automated software. COS patients (n=98; 234 scans) had significantly lower right (p=0.003), left (p<0.001), and total (p<0.001) insular volumes than healthy volunteers (n=100; 248 scans). Right insular volume negatively correlated with positive symptoms as measured by the Scale for the Assessment of Positive Symptoms (SAPS) (p=0.02), while both left (p=0.01) and right (p=0.006) insula volumes were positively correlated with overall functioning, as measured by the Children's Global Assessment Scale (CGAS) scores. COS siblings (n=71; 153 scans), on the other hand, did not differ significantly from normal volunteers suggesting that the insular deficits are more related to the illness state than a familial endophenotype. These results also highlight the salience of the insula in positive symptoms of schizophrenia perhaps resulting from the inability to discriminate between self from the non-self in COS. Further work to connect insular deficits to other neurocircuitries is warranted.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States. Electronic address: marcel.moran@nih.gov.
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Moran
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Weisinger
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Katharine
authors.initials: K
authors.lastname: Ludovici
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Harrison
authors.initials: H
authors.lastname: McAdams
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Pete
authors.initials: P
authors.lastname: Gochman
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Judith
authors.initials: J
authors.lastname: Rapoport
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, NIH, United States.
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
mesh_terms: D000293:Adolescent; D002540:Cerebral Cortex / Q000254:growth & development* / Q000473:pathology*; D002547:Cerebral Palsy / Q000209:etiology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008279:Magnetic Resonance Imaging; D012016:Reference Values; D015518:Rett Syndrome / Q000209:etiology / Q000473:pathology; D012561:Schizophrenia, Childhood / Q000150:complications* / Q000473:pathology*; D035781:Siblings; D018980:Williams Syndrome / Q000209:etiology / Q000473:pathology
keywords: Neuroimaging; Psychiatry; Psychosis; Schizophrenia