title: Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals.
abstract: BACKGROUND
  Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.
  
  
  METHODS
  Participants underwent baseline magnetic resonance imaging and were followed-up over 12-24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR individuals who developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and healthy control subjects (n = 33).
  
  
  RESULTS
  Relative to control subjects, UHR-P individuals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP individuals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by individuals subsequently diagnosed with a schizophrenia spectrum psychosis.
  
  
  CONCLUSIONS
  These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR individuals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to individuals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker.
authors.affiliation: Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne, Carlton South, Victoria, Australia. fornitoa@unimelb.edu.au
authors.forename: Alex
authors.initials: A
authors.lastname: Fornito
authors.forename: Alison R
authors.initials: AR
authors.lastname: Yung
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Phillips
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.forename: Sue
authors.initials: S
authors.lastname: Cotton
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.forename: Murat
authors.initials: M
authors.lastname: Yücel
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001931:Brain Mapping; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D011618:Psychotic Disorders / Q000235:genetics* / Q000473:pathology*; D012306:Risk; D012565:Schizophrenic Psychology; D055815:Young Adult