- Human pathology

Home > E. Pathology by systems > Nervous system > Central nervous system > Brain > schizophrenia


Monday 22 September 2003

Schizophrenia, which affects about 1.5 percent of the U.S. population, can result in a variety of symptoms that include disrupted thinking, hallucinations, delusions and abnormal speech. The disease is thought to have genetic links but usually does not manifest itself until adolescence or early adulthood.


Initial gene links for schizophrenia were reported nearly a decade ago, after researchers at Julius-Maximilian University of Würzburg in Germany found a common mutation on the chromosome 22 in the protein-encoding gene WKL1.

Schizophrenia involves some of the same genetic variations as autism and attention deficit disorders.

In an effort to assess some of the common genetic variations that might underpin this fairly common but thorny mental illness, researchers sequenced DNA from 1,735 adults with schizophrenia and 3,485 healthy adults.

Across the patients that had the disease, the researchers found many frequent variations related to copying or deleting genes, known as copy-number variations (CNVs).

And among the genes that were more likely affected by these changes in schizophrenic individuals were CACNA1B and DOC2A, which help make proteins for calcium signals that regulate neurotransmitters in the brain. Two other more common variations, in RET and RIT2, would likely impact brain development.

These genes affect synaptic function, so deletions or duplications in those genes may alter how brain circuits are formed.

Previous research had turned up a few rare copy-number variations (CNVs) in schizophrenic patients, but they explain only a small fraction of the genetic risk of this common complex disease. A work confirmed higher rates of variations in some of the same networks disturbed in people with autism and attention deficit disorders.

Variant genes

- WKL1
- RIT2

Susceptibility loci

- DISC1 at 1q42.1 (MIM.605210)
- 6p22.3: variants in gene DTNBP1 coding for dysbindin (dystrobrevin-binding protein 1) (12474144, 12098102)
- 6q23.2: Polymorphisms in the Trace Amine Receptor 4 (TRAR4)
- 7q22 (107673293)
- 8p23.3-p21.2: variants in gene coding for neuroregulin-1 (12145742, 16400611)
- 10q22 (12929083)
- 11p13.1-q14.1 (16400611)
- 11q22-24: FXYD6 gene, encoding phosphohippolin (17357072)
- 22q11 : catechol-O-methyltransferase (COMT) gene (12802784, 12402217)
- Xp22.3
- variants in gene coding forneuregulin 1 (NRG1) (12478479)


- Schizophrenia shares genetic links with autism, genome study shows, Scientific american, May 10, 2010

- Bipolar disorder and schizophrenia are genetically linked, Scientific American, Jan 15, 2009


- Romanticism and schizophrenia. Second part: The intimacy hypothesis. López-Ibor JJ, López-Ibor MI. Actas Esp Psiquiatr. 2014 Sep;42(5):201-27. PMID: 25179093 (Free)


- Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajós M. Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev Drug Discov. 2008 Jan;7(1):68-83. PMID: 18064038

- Porteous DJ, Millar JK. Disrupted in schizophrenia 1: building brains and memories. Trends Mol Med. 2006 Jun;12(6):255-61. PMID: 16679065

- Owen MJ, Craddock N, O’Donovan MC. Schizophrenia: genes at last? Trends Genet. 2005 Sep;21(9):518-25. PMID: 16009449

- Sundram S, Joyce PR, Kennedy MA. Schizophrenia and bipolar affective disorder: perspectives for the development of therapeutics. Curr Mol Med. 2003 Aug;3(5):393-407. PMID: 12942993

- Selemon LD, Rajkowska G. Cellular pathology in the dorsolateral prefrontal cortex distinguishes schizophrenia from bipolar disorder. Curr Mol Med. 2003 Aug;3(5):427-36. PMID: 12942996

- Dean B, Bymaster FP, Scarr E. Muscarinic receptors in schizophrenia. Curr Mol Med. 2003 Aug;3(5):419-26.
PMID: 12942995

- Van den Buuse M, Garner B, Koch M. Neurodevelopmental animal models of schizophrenia: effects on prepulse inhibition. Curr Mol Med. 2003 Aug;3(5):459-71. PMID: 12942999

- Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005 Apr;6(4):312-24. PMID: 15803162

- O’Donovan MC, Williams NM, Owen MJ. Recent advances in the genetics of schizophrenia. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R125-33. PMID: 12952866

- Freedman R. Schizophrenia. N Engl J Med. 2003 Oct 30;349(18):1738-49. PMID: 14585943

- Lewis DA, Levitt P. Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci. 2002;25:409-32. PMID: 12052915

- Bray NJ, Owen MJ. Searching for schizophrenia genes. Trends Mol Med. 2001 Apr;7(4):169-74. PMID: 11286941