Drug Discovery for Schizophrenia
CHAPTER 2: The Impact of Epigenetics in Schizophrenia Research
Published:28 Apr 2015
Special Collection: 2015 ebook collection , 2011-2015 industrial and pharmaceutical chemistry subject collectionSeries: Drug Discovery
“It is all in the genes” was the general belief of many researchers in molecular biology for a long time. It spurred the imagination to find the keys for any disease in the sequence of the DNA and set in motion huge efforts to develop more and more advanced technologies for sequencing whole genomes within increasingly shorter timescales. The general consensus that mental disorders are multigenic in origin resulted in the abandonment of the sequencing of single candidate genes and directed the attention to studies of genome-wide association studies (GWASs) of single or multiple mutations (single nucleotide polymorphisms, SNPs) and to genome-wide complex trait analysis (GCTA). These approaches are discussed here in comparison with investigations aimed at understanding molecular mechanisms encoding the epigenome. It has already become very clear that the latter mechanisms are faster and more flexible than alterations inserted in the genome, but—almost expectedly—orders of magnitude more complex. Alongside the DNA methylome, we have to consider the incredibly high variability concealed in the histone code, the mutual interactions of both in response to environmental influences and their potential to be heritable. These features open up plenty of room for “writing”, “erasing” and storage of new information from the environment without changing the DNA sequence. Schizophrenia is believed to be a developmental disorder and, hence, is moulded in its progression by ample environmental impact. Consequently, this and other psychiatric disorders appear to bear a strong epigenetic component on top of less significant genetic predisposition.