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Annotation

McGrath JA, Avramopoulos D, Lasseter VK, Wolyniec PS, Fallin MD, Liang KY, Nestadt G, Thornquist MH, Luke JR, Chen PL, Valle D, Pulver AE. Familiality of novel factorial dimensions of schizophrenia. Arch Gen Psychiatry . 2009 Jun 1 ; 66(6):591-600. PubMed Abstract

Comments on Paper and Primary News
Primary News: Nine Dimensions of Schizophrenia Found to Run in Families

Comment by:  John McGrath, SRF Advisor
Submitted 24 June 2009 Posted 24 June 2009

John A. McGrath and I (John J. McGrath—no relation) welcome any other like-named or like-minded researchers to contribute further to the quest to resolve the heterogeneity of the poorly understood group of brain disorders currently lumped under the label “schizophrenia.” This interim label has tenaciously guided our research efforts for decades, despite the fact that the research community is well aware of its deficiencies. Like intellectual fly-paper, the problems with this diagnostic label have probably shortened the life of many able researchers. Can we ever hope to fractionate the underlying disorders into more meaningful groupings?

John A. McGrath and colleagues from Baltimore have looked for heritability of a broad range of symptoms and measures of disability. All factors were found to be heritable, but some were more heritable than others. This is an interesting outcome. The challenge for the research community will be what to do next.

I would like to add a few friendly comments in order to stimulate debate. These comments reflect my personal biases. I...  Read more


View all comments by John McGrath

Primary News: Nine Dimensions of Schizophrenia Found to Run in Families

Comment by:  Timothea Toulopoulou
Submitted 15 July 2009 Posted 15 July 2009

While a number of genetic loci that appear to represent an increased susceptibility to schizophrenia have been identified, linkage, candidate gene and whole genome scan approaches have been largely unsuccessful in identifying these genes in any consistent way. This is partly because the clinical characteristics of schizophrenia are very far along the pathophysiological chain that extends from genes, through proteins, neurons, cognition, behavior, and symptoms, and finally to the DSM-IV construct of schizophrenia. Phenotypes closer to the gene effects in the pathophysiological pathway are better placed to help to untangle the genetic components of the illness.

McGrath and colleagues analyses of 73 indicators resulting in nine sign and symptom factors, or dimensions, could provide alternative phenotypes for molecular genetic studies in place of the DSM-IV construct of schizophrenia, assuming, of course, that twin and adoption studies show that they are heritable. McGrath and colleagues used a large number of core symptoms of schizophrenia and additional indicators of...  Read more


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