DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.
BACKGROUND
DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology.


METHODS
We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy volunteers (N=25) and positive and negative symptoms in 200 patients with schizophrenia.


RESULTS
Among patients and healthy volunteers, phe carriers (N=11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N=144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N=56).


CONCLUSIONS
These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.
Szeszko
Philip R
PR
Feinstein Institute for Medical Research, Manhasset, NY, USA. szeszko@lij.edu
Hodgkinson
Colin A
CA
Robinson
Delbert G
DG
Derosse
Pamela
P
Bilder
Robert M
RM
Lencz
Todd
T
Burdick
Katherine E
KE
Napolitano
Barbara
B
Betensky
Julia D
JD
Kane
John M
JM
Goldman
David
D
Malhotra
Anil K
AK
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000473:pathology*; D012565:Schizophrenic Psychology
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins