Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals.
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.
Fornito
Alex
A
Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne, Carlton South, Victoria, Australia. fornitoa@unimelb.edu.au
Yung
Alison R
AR
Wood
Stephen J
SJ
Phillips
Lisa J
LJ
Nelson
Barnaby
B
Cotton
Sue
S
Velakoulis
Dennis
D
McGorry
Patrick D
PD
Pantelis
Christos
C
Yücel
Murat
M
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