A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.
BACKGROUND
Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined.


METHODS
Magnetic resonance imaging was performed in 31 neuroleptic-naïve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes.


RESULTS
Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms.


CONCLUSIONS
These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.
Gur
Raquel E
RE
Department of Psychiatry, Schizophrenia Research Center, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
Kohler
Christian
C
Turetsky
Bruce I
BI
Siegel
Steven J
SJ
Kanes
Stephen J
SJ
Bilker
Warren B
WB
Brennan
Avis R
AR
Gur
Ruben C
RC
D000328:Adult; D000342:Affective Symptoms / Q000175:diagnosis / Q000209:etiology*; D000679:Amygdala / Q000473:pathology* / Q000503:physiopathology; D000886:Anthropometry; D005260:Female; D005625:Frontal Lobe / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000150:complications* / Q000175:diagnosis / Q000473:pathology*; D012720:Severity of Illness Index; D012727:Sex Characteristics