An evolutionary approach reveals new clues toward understanding the roots of schizophrenia

Is mental illness simply the evolutionary toll humans have to pay in return for our unique and superior cognitive abilities when compared to all other species? But if so, why have often debilitating illnesses like schizophrenia persisted throughout human evolutionary history when the affects can be quite negative on an individual's chances of survival or reproductive success?

In a new study appearing in Molecular Biology and Evolution, Mount Sinai researcher Joel Dudley has led a new study that suggests that the very changes specific to may have come at a cost, contributing to the genetic architecture underlying traits in modern humans.

"We were intrigued by the fact that unlike many other mental traits, schizophrenia traits have not been observed in species other than humans, and schizophrenia has interesting and complex relationships with human intelligence," said Dr. Joel Dudley, who led the study along with Dr. Panos Roussos. "The rapid increase in genomic data sequenced from large schizophrenia patient cohorts enabled us to investigate the molecular evolutionary history of schizophrenia in sophisticated new ways."

The team examined a link between these regions, and human-specific evolution, in genomic segments called human accelerated regions, or HARs. HARs are short signposts in the genome that are conserved among non-human species but experienced faster mutation rates in humans. Thus, these regions, which are thought to control the level of gene expression, but not mutate the gene itself, may be an underexplored area of research.

The team's research is the first study to sift through the human genome and identify a shared pattern between the location of HARs and recently identified schizophrenia gene loci. To perform their work, they utilized a recently completed, largest schizophrenia study of its kind, the Psychiatric Genomics Consortium (PGC), which included 36,989 schizophrenia cases and 113,075 controls. It is the largest genome-wide association study ever performed on any psychiatric disease.

They found that the schizophrenic loci were most strongly associated in genomic regions near the HARs that are conserved in non-human primates, and these HAR-associated schizophrenic loci are found to be under stronger evolutionary selective pressure when compared with other schizophrenic loci. Furthermore, these regions controlled genes that were expressed only in the prefrontal cortex of the brain, indicating that HARs may play an important role in regulating genes found to be linked to schizophrenia. They specifically found the greatest correlation between HAR-associated schizophrenic loci and genes controlling the expression of the neurotransmitter GABA, brain development, synaptic formations, adhesion and signaling molecules.

Their new evolutionary approach provides new insights into schizophrenia, and genomic targets to prioritize future studies and drug development targets. In addition, there are important new avenues to explore the roles of HARs in other mental diseases such as autism or bipolar disorder.


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Journal information: Molecular Biology and Evolution

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Feb 24, 2015
The paper "Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions" is free and can be found in a link with its abstract http://mbe.oxford...5e60131b

Feb 25, 2015
The most likely genetic solution is that schizophrenia is a combination of traits which are all independently beneficial.

Consider this analogy. In a particular species, having bigger legs is an advantage for fast getaway. But having a lighter body with smaller organs, including a smaller heart, also allows for quick getaway from predators.

But inheriting the genes for smaller body and bigger legs leads to heart failure and other diseases.

So how is evolution going to eliminate heart failure in this species? It can't.

In the human, there are several cognitive abilities that are independently beneficial but which in combination are deadly. A drug that targets any one of these abilities and reduces it is likely to also reduce or eliminate schizophrenia. (cont below)

Feb 25, 2015
bilities such as being able to associate otherwise unrelated phenomena or events is fundamental to science and technology.

An ability to extrapolate and generalisation an observation in one context to all possible manifestations is almost a mandatory requirement for physics papers.

Having the feeling that there is a need to explore and understand in order to be a complete person is what we describe as a driven person and has led explorers to discover and mountains to be conquered.

Having an ability to internalise elements of the environment and see them evolve in the imagination alone is an essential element of the basic thought experiment.

But what would happen if any three or more of the above were to be exemplary in the same individual?

Little wonder, then, that half of Einstein's sons were schizophrenic.

Feb 25, 2015
@Squirrel

Only the abstract is free...

"You may access this article for 1 day for US$39.00. "

Feb 28, 2015
If a gene produces the schizophrenia,the main notion of this research claims that there is a functional mutation in the gene without any changes in the structure of gene itself.
But the question;
What is characteristics of functional mutation in any gene which lead to the inner schizophrenic symptoms "like hearing voices" ?

Feb 28, 2015
The person without schizophrenia can perceive his thoughts by implied way" soundless",while the person with schizophrenia perceives his thoughts by vocal way,wherever the thoughts has becomes audible vocal thoughts ,the question;
What is characteristics of any functional mutation in any gene which convert the implied thoughts into audible vocal thoughts ?

Feb 28, 2015
In sum,it is possible to prove an existence of many functional mutation in some human genes,but in practice it is impossible to prove a causality relation between them characteristics and nature of inner symptoms of schizophrenia " existential fixed symptoms" because;
until now,there is no available scientific tolls in the lab be able to diagnosis the inner fixed symptoms "moved imaginary pictures,heard voices and the inner dialogues which occur in the person's mind"
This means that,the main symptoms of schizophrenia is hidden , unknown and non diagnosis for the researchers,so that prove the relation between the genetic mutation and the existential symptoms of schizophrenia is not available now !

Mar 02, 2015
In reality,there are a new mental processes that happen in the brain regions and conscious existence of the schizophrenic person
2-We can considering these processes as existential and functional mutation
3- They are a futures of mutation, because they are not founded or occurred in all human beings without schizophrenia
4-These new processes have huge effects on all aspects of normal mental functions,they causing all types of disorders in pathway of normal mental processes,emotion,sensation and usual behaviors,,add for that they have
unexpected effectiveness on the frame/content of all cognitive processes
5-We are focus on a new existential mutation which causing a new type of mental processes,which in turn causing all types of disorders in the pathway /content of all original normal mental processes,emotion,sensation and behavior directions
6- Emergence of the new mental processes in mind-brain of the person is the starting point of the schizophrenia events in the brain

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