CIMH: Increased genetic load for schizophrenia identified in treatment

This question is the focus of an international research consortium (CRESTAR), in collaboration with scientists from the CIMH. Among others the researchers aimed to elucidate whether medication efficacy in schizophrenia can be predicted by attributes that can be assessed prior to treatment initiation. First results indicate that medication will be less effective in patients who carry more risk genes for schizophrenia. The study has now been published in the scientific journal Molecular Psychiatry.

Schizophrenia is a major psychiatric disorder, often characterized by a chronic progression in symptoms. This in turn leads to pronounced psychosocial impairment and the requirement for permanent care.
At present, psychiatrists are unable to predict which medication will be effective in a given schizophrenia patient.

The EU-funded CRESTAR project (http://www.crestar-project.eu) aims to investigate this research topic. A particular focus of its research work is a highly potent antipsychotic medication, Clozapine, which has been available since decades. Clozapine however, is only used after at least two trials of other medications have proven to be unsuccessful, as in a small number of cases life-threatening side-effects arise. This approach leads to a delay in effective treatment and a worsening of long-term prognosis.

The CRESTAR researchers are now investigating: First, whether clear indicators for the development of these adverse effects can be identified at an earlier time-point; and second whether clozapine will be effective in a given individual patient. Identification of these factors would allow the safe and effective initiation of clozapine during the early stages of illness.

CRESTAR researchers used information concerning many thousands of genetic markers to show that antipsychotic medication in general will be less effective in patients with a higher genetic load for schizophrenia. This genetic load is already present at birth. Despite the existence of familial schizophrenia, most schizophrenia patients have no family history of the disease. Thus a genetic test to determine the genetic load would represent a first step towards individualized therapy.

Until present psychiatric genetic research has generated few results of direct relevance to treatment, and individual prediction is still not possible. The results of the present study are only a small step into this direction. According to the first author of this recent CRESTAR study, Josef Frank, this is likely to change in the future, since through the development of new biostatistical methods, an increasing amount of information is being obtained concerning genetic variation across the whole genome.

Publication:
Identification of increased genetic risk scores for schizophrenia in treatment resistant patients.
Josef Frank, Maren Lang, Stephanie H Witt, Jana Strohmaier, Dan Rujescu, Sven Cichon, Franziska Degenhardt, Markus M Nöthen, David A Collier, Stephan Ripke, Dieter Naber & Marcella Rietschel. Molecular Psychiatry (2014). doi:10.1038/mp.2014.56

Contact at the CIMH:
Prof. Dr. Marcella Rietschel
Central Institute of Mental Health
Department of Genetic Epidemiology in Psychiatry
E-Mail: marcella.rietschel@zi-mannheim.de

http://www.zi-mannheim.de