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September 14, 2004
New Direction in Genetic Research in Schizophrenia
Most genetic researchers in schizophrenia believe that there is substantial evidence that this group of disorders involves mutations in the nucleotide sequence of several genes, resulting in abnormal messenger ribonucleic acid (mRNA) (transcription) and therefore abnormal proteins (translation). However, nongenetic factors such as stress, social environment, learning etc., can also modify the expression of a protein by altering the transcription of normal genes. This epigenetic regulation may contribute to the etiology of the schizophrenias. It is proteins that ultimately define the functioning of brain cells, and protein expression can be regulated by epigenetic processes. Pesold, Roberts and Kirkpatrick (2004) noted: “Measuring proteins or the transcripts that encode them may therefore be fruitful in fully understanding the pathology of schizophrenia” (p. 273 in Textbook of Biological Psychiatry, edited by Jaak Panksepp and published by Wiley-Liss).
As I pointed out in previous postings, microassay analysis simultaneously can compare relative levels of thousands of gene transcripts in postmortem tissue. This technology is fairly recent and is now being applied to persons having been diagnosed with schizophrenia. The studies already conducted (Mirnics et al 2001-Analysis of complex brain disorders with gene expression microassays: Schizophrenia as a disease of the synapse. Trends in Neuroscience 24:479-486) have revealed changes in the expression of gene transcripts with developmental relevance including transcription factors, receptors, genes important for myelination, as well as a host of proteins involved in synaptic functioning and neurotransmission.
I think this research on gene expression will one day contribute to the growing awareness of the importance of the environment, in particular, the social and relational environment, in the neurobiology of severe mental illness. Affective processes may then be given greater attention in terms of etiology. My own view is that the schizophrenias are emotionally based disorders (affective disorders with secondary cognitive alterations-much as Luc Ciompi has described in his volume and papers on affect-logic).
As Jaak Panksepp (2004), neuroscientist and author of Affective Neuroscience by Oxford University Press, noted in his recent edited volume Textbook of Biological Psychiatry:
"A fuller ecognition of basic emotional imbalances of many psychiatric disorders may also help reverse a growing problem of modern psychiatry -- the marginalization of patients by making them mere consumers of pills rather than agents in reconstructing meaningful human relationships and life insights...perhaps through some type of Meyerian 'sociopsychobiological' synthesis. Obviously, psychiatric disorders will continue to be permeated and modified by hosts of meta-emotional factors-above all, individual capacities for affective self-regulation and thoughtfulness" (pp. 18-19).
Brian Koehler PhD
New York University
80 East 11th Street #339
New York NY 10003
212.533.5687
brian_koehler@psychoanalysis.net
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