Abstract
Research into the genomics of schizophrenia promises much, but so far is resplendent with failures to replicate, and has yielded little of therapeutic potential. Within our bodies resides a dynamic population of gut microbes forming a symbiotic superorganism comprising a myriad of bacteria of approximately 1014 cells, containing 100 times the number of genes of the human genome and weighing approximately the same as the human brain. Recent preclinical investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. We are pivotally dependent on the neuroactive substances produced by such bacteria. The biological diversity of this ecosystem is established in the initial months of life and is highly impacted upon by environmental factors. To date, this vast quantity of DNA has been largely ignored in schizophrenia research. Perhaps it is time to reconsider this omission.
The present classification of psychotic illness owes much to the work of Emil Kraepelin1 and he observed the fact that psychotic illness tended to run in certain families. Since then twin and adoption studies have provided further support for the view that schizophrenia is frequently a disorder with a genetic basis. It is generally accepted that the concordance rate in monozygotic twins is greater than that observed in dizygotic twins,2,3 and adopted children of schizophrenic parents have the same risk of schizophrenia as their biological rather than their adoptive parents.4,5 In recent years the availability of high-throughput, relatively inexpensive, sequencing technology has enabled a detailed exploration of the molecular genetics of schizophrenia in large patient populations.6,7 Risk loci have been identified from both genome-wide association8,9 and copy number variant studies.10,11 However, the field since its inception is resplendent with claims, counterclaims and major failures to replicate.12, 13, 14 Even more recent findings that have been replicated account for only a fraction of the heritability. In this article we explore the view that the genomic analysis of schizophrenia to date has been far too limited, and fails to capture the true genomic diversity of the human body.
Within our bodies resides a dynamic population of microbes forming a symbiotic super-organism with whom we have co-evolved.15 Recent investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. The collective microbiome comprises a myriad of bacteria of approximately 1014 cells, containing 100 times the number of genes of the human genome.15,16 Despite evolution of this microbiome for 500 million years,17,18 only recent advances in sequencing technology have allowed us to appreciate the full complexity of the host–microbe interrelationship. The gut microbiota is a highly developed organ of immense metabolic complexity and has approximately the same weight as the human brain. It is now clear that the gut microbiota plays a key role in the life and health of the host by protecting against pathogens, metabolizing dietary nutrients and drugs, and influencing the absorption and distribution of dietary fat.17 However, the influence of the microbiota extends beyond the gastrointestinal tract, playing a major role in the development and functioning of the central nervous system (CNS).19, 20, 21 Among the many substances produced by the gut microbiota are key central neurotransmitters whose influence extends beyond the enteric nervous system to the brain. To date no effort has been made to analyse this complex genomic structure in schizophrenia or other complex psychiatric disorders.
http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201493a.html