DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia.

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.
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.
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).
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.
AuthorsPhilip R Szeszko, Colin A Hodgkinson, Delbert G Robinson, Pamela Derosse, Robert M Bilder, Todd Lencz, Katherine E Burdick, Barbara Napolitano, Julia D Betensky, John M Kane, David Goldman, Anil K Malhotra
JournalBiological psychology (Biol Psychol) Vol. 79 Issue 1 Pg. 103-10 (Sep 2008) ISSN: 0301-0511 [Print] Netherlands
PMID18078707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • DISC1 protein, human
  • Nerve Tissue Proteins
  • Adult
  • Cohort Studies
  • Female
  • Frontal Lobe (pathology)
  • Genotype
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Nerve Tissue Proteins (genetics, physiology)
  • Polymorphism, Genetic (genetics)
  • Prefrontal Cortex (pathology)
  • Psychiatric Status Rating Scales
  • Schizophrenia (pathology)
  • Schizophrenic Psychology

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: