Schizophrenia: One Coat of Many Colors

John Smythies

doi:10.3389/fpsyt.2013.00043

Abstract

For a long while the scientific picture of the biochemical origins of schizophrenia presented a large number of apparently quite unconnected isolated findings. Recently however a clearer account has emerged that begins to tie most of these facts together into a single coherent account. In other words, in most cases, a single complex mechanism seems to be involved. The earlier attempts at providing a single hypothesis – for example the transmethylation, dopamine (DA), serotonin, redox, and glutamate hypotheses – are coming to be seen as parts of an interlinked whole.

Highlights

For a long while the scientific picture of the biochemical origins of schizophrenia presented a large number of apparently quite unconnected isolated findings
Genes The genetic basis of schizophrenia is complex and does not follow the Mendelian model. Instead it is based on the interactive effect of a large number of abnormal genes each with a single nucleotide polymorphism (SNP) and only a minor impact (Brennand and Gage, 2011)
Of these SNPs, 138 are known to participate in 100 unique genes that regulate four neurotransmitter pathways – GABA receptor signaling, DA receptor signaling, neuroregulin signaling and glutamate receptor signaling – all processes known to be involved in schizophrenia

Summary

Introduction

For a long while the scientific picture of the biochemical origins of schizophrenia presented a large number of apparently quite unconnected isolated findings. To give a couple of examples out of many to illustrate the complexity of the system: one recent study found 253 SNPs in a population of 92 schizophrenic patients (Chen et al, 2012) Of these SNPs, 138 are known to participate in 100 unique genes that regulate four neurotransmitter pathways – GABA receptor signaling, DA receptor signaling, neuroregulin signaling and glutamate receptor signaling – all processes known to be involved in schizophrenia. The mechanisms include DNA methylation and demethylation, acetylation of histones, chromatin-modeling, mRNA splicing/editing, and translation, ribosome biogenesis and, last but not least, microRNAs (Millan, 2012) Many of these epigenetic processes themselves are controlled by synaptic action (Wang and Zhuo, 2012) allowing synaptic control of an extensive range of epigenetic process, that in turn modulate the protein synthesis that is essential for the growth and development of synapses, the dendritic tree and dendritic spines, neural plasticity, long term learning and memory. MicroRNAs MicroRNAs (miRNA) are short RNAs that control the function of their target messenger RNAs by binding to them by base www.frontiersin.org

Schizophrenia update

Conclusion