Apr 24, 2012
@12:41 PM

Schizophrenia and genetics

I received the below questions in regards to this paper that I first published online in 2009 and in the print version of the journal in 2011, for this paper:

Lyon, G.J., Moore, H.,Lieberman, J.A., Abi-Dargham, A., Javitch, J. and Sulzer, D., (2009). Presynaptic regulation of dopamine transmission in schizophrenia. Schizophrenia Bulletin. 2011 Jan;37(1):108-17. Epub 2009 Jun 12

1.) How can repeated use of amphetamines lead to a state similar to schizophrenia?
2.) What effects can an accumulation of dopamine have on the striatum?
3.) How can progressively high elevations of presynaptic striatal dopamine contribute to poorer clinical response to antipsychotic medications after each psychotic episode?

I spent three years researching and writing this paper, from 2006-2009. During that time and since then, I have come to realize that schizophrenia is a syndrome likely comprised of hundreds of different genetic diseases. Therefore, only certain people may become psychotic or get worse with amphetamines. In fact, I now believe that many of the papers that I cited in my 2009 review were vastly underpowered, given that they usually only had a few dozen patients with this syndrome “schizophrenia”, with no attempt to break them down into genetic components, mainly because we are still trying to figure out the genetic basis of ~90% of these cases. My review in 2009 was an attempt to synthesize the literature available at that time, but it proved to be a herculean task particularly due to this lack of homogeneity with this syndrome we currently call schizophrenia.