0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Genetic Linkage in Schizophrenia
JAMES S. BROWN, Jr., M.D.
Am J Psychiatry 2003;160:598-598. doi:10.1176/appi.ajp.160.3.598

To the Editor: After not finding a susceptibility gene for schizophrenia, Dr. DeLisi et al. suggested that schizophrenia could result from variation in gene expression. They also recommended that investigators who choose candidate genes for schizophrenia take under consideration various defects observed in schizophrenia. I wish to add three additional recommendations.

First, successful identification of candidate genes for schizophrenia may be enhanced if the higher urban prevalence of schizophrenia is considered. Second, a variation of genetic expression could result from a pathological mechanism known as translational pathophysiology (1). Abnormalities of protein translation could allow genetic, infectious, and nutritional pathways to affect brain development. Third, investigators might consider that a schizophrenia gene enhances survival during prenatal growth.

Translational pathophysiology could result in both enhanced survival and schizophrenia if a gene that provides resistance to an infectious agent through translational interference is expressed during fetal growth and inhibits both viral and host proteins. I hypothesized this Darwinian approach in merging the literature on the flavivirus resistance gene with the geographies of schizophrenia and flaviviruses (2). In this context, the genetic resistance of certain mice to typhoid fever may also have application to schizophrenia. A critical genetic control of typhoid resistance is the natural resistance-associated macrophage protein 1 (NRAMP 1) (3). This gene enhances expression of several proteins, is expressed in neurons, and is associated with behavioral and immune responses to stress (4, 5). The human homologue maps to chromosome 2q35 (3), a location also linked to susceptibility to rheumatoid arthritis (4). Given the controversial hypothesis that persons with schizophrenia are resistant to rheumatoid arthritis, it is noteworthy that chromosome 2 was one of the few chromosomes in which Dr. DeLisi et al. found positive linkages.

Philips AV, Cooper TA: RNA processing and human disease. Cell Mol Life Sci  2000; 57:235-249
[PubMed]
[CrossRef]
 
Brown JS Jr: A novel mechanism to explain protein abnormalities in schizophrenia based on the flavivirus resistance gene. Mol Psychiatry  2001; 6:701-711
[PubMed]
[CrossRef]
 
Dunstan SJ, Ho VA, Duc CM, Lanh MN, Phuong CX, Luxemburger C, Wain J, Dudbridge F, Peacock CS, House D, Parry C, Hien TT, Dougan G, Farrar J, Blackwell JM: Typhoid fever and genetic polymorphisms at the natural resistance-associated macrophage protein 1. J Infect Dis  2001; 183:1156-1160
[PubMed]
[CrossRef]
 
Shaw MA, Clayton D, Atkinson SE, Williams H, Miller N, Sibthorpe D, Blackwell JM: Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35. J Med Genet  1996; 33:672-677
[PubMed]
[CrossRef]
 
Evans CA, Harbuz MS, Ostenfeld T, Norrish A, Blackwell JM: Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress. Neurogenetics  2001; 3:69-78
[PubMed]
[CrossRef]
 
+

References

Philips AV, Cooper TA: RNA processing and human disease. Cell Mol Life Sci  2000; 57:235-249
[PubMed]
[CrossRef]
 
Brown JS Jr: A novel mechanism to explain protein abnormalities in schizophrenia based on the flavivirus resistance gene. Mol Psychiatry  2001; 6:701-711
[PubMed]
[CrossRef]
 
Dunstan SJ, Ho VA, Duc CM, Lanh MN, Phuong CX, Luxemburger C, Wain J, Dudbridge F, Peacock CS, House D, Parry C, Hien TT, Dougan G, Farrar J, Blackwell JM: Typhoid fever and genetic polymorphisms at the natural resistance-associated macrophage protein 1. J Infect Dis  2001; 183:1156-1160
[PubMed]
[CrossRef]
 
Shaw MA, Clayton D, Atkinson SE, Williams H, Miller N, Sibthorpe D, Blackwell JM: Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35. J Med Genet  1996; 33:672-677
[PubMed]
[CrossRef]
 
Evans CA, Harbuz MS, Ostenfeld T, Norrish A, Blackwell JM: Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress. Neurogenetics  2001; 3:69-78
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 6.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 38.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
APA Guidelines
PubMed Articles
Genetics of Psychosis in Alzheimer Disease. Curr Genet Med Rep 2014;2(1):30-38.