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

AbstractBACKGROUND:
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).
DISCUSSION:
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
Topics
  • 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

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