Evolution of schizophrenia

The evolution of schizophrenia refers to the theory of natural selection working in favor of selecting traits that are characteristic of the disorder. Positive symptoms are features that are not present in healthy individuals but appear as a result of the disease process. These include visual and/or auditory hallucinations, delusions, paranoia, and major thought disorders. Negative symptoms refer to features that are normally present but are reduced or absent as a result of the disease process, including social withdrawal, apathy, anhedonia, alogia, and behavioral perseveration. Cognitive symptoms of schizophrenia involve disturbances in executive functions, working memory impairment, and inability to sustain attention. The evolution of schizophrenia refers to the theory of natural selection working in favor of selecting traits that are characteristic of the disorder. Positive symptoms are features that are not present in healthy individuals but appear as a result of the disease process. These include visual and/or auditory hallucinations, delusions, paranoia, and major thought disorders. Negative symptoms refer to features that are normally present but are reduced or absent as a result of the disease process, including social withdrawal, apathy, anhedonia, alogia, and behavioral perseveration. Cognitive symptoms of schizophrenia involve disturbances in executive functions, working memory impairment, and inability to sustain attention. Given the high numbers of individuals diagnosed with schizophrenia (nearly 1% of modern-day populations), it is unlikely that the disorder has arisen solely from random mutations. Instead it is believed that, despite its maladaptive nature, schizophrenia has been either selected for throughout the years or exists as a selective by-product. The balancing selection hypothesis suggests that balancing selection, an evolutionary mechanism, has allowed for the persistence of certain schizophrenia genes. This mechanism is defined as maintaining multiple alleles of a gene in the gene pool of a population despite having selective pressures. Heterozygote advantage, a mechanism of balancing selection, is when the presence of both the dominant and recessive allele for a particular gene allow for greater fitness in an individual as compared to if the individual only expressed one type of allele. This mechanism can be seen in the carriers for the schizophrenia gene who express both the dominant and recessive allele. These carriers may express certain advantageous traits that would allow the schizophrenia gene to be selected for. Evidence has suggested a carrier of the schizophrenia gene could experience selective advantage due their expression of advantageous traits as compared to those who do not express the schizophrenia gene. Studies have shown that some of the carriers for the schizophrenia gene may express adaptive benefits such as a decreased frequency of viral infections. Additional beneficial traits may include a higher IQ, increased creativity, and mathematical reasoning. Due to the presence of these beneficial traits, the schizophrenia gene has not been selected against and has remained prevalent in human development over numerous generations. While the idea of balancing selection hypothesis sounds plausible, there is no substantial evidence in support of this hypothesis. Within the studies that found a positive correlation between specific favorable characteristics and the schizophrenia gene, only a few carriers were tested, meaning that there is no sufficient evidence to assume a direct correlation between these advantageous traits and the carriers of schizophrenia. Although this hypothesis has not yet been substantiated, the advantageous traits that these carriers express could provide a reasonable explanation for why the genes for schizophrenia have not been eliminated. Positive selection is another mechanism that has allowed for the selection of genes contributing to the presence of schizophrenia. Positive selection is a mechanism of natural selection in which beneficial traits are selected for and become prevalent over time in a population. In a study conducted using phylogeny-based maximum-likelihood (PAML), a method that was used to test for positive selection, significant evidence of positive selection was found in the genes associated with schizophrenia. An example of a beneficial trait that has been selected for through positive selection is creativity. Three allelic variants of creativity genes that are also associated with schizophrenia include SLC6A4, TPH1 and DRD2. The high inheritance of creative and cognitive characteristics by these allelic variants in individuals expressing schizophrenia confirms evidence of positive selection within some schizophrenia genes. Additional studies conducted using SNP analysis on the SLC39A8 gene, a gene associated with Schizophrenia, found that the T-allele on the gene was associated with reduced blood pressure and a decreased risk of hypertension. These beneficial traits associated with schizophrenia genes provide a reason for why these genes have been selected for in human development. While promising evidence persists, additional evidence claims that the effect of positive selection may not play a significant role in the presence of schizophrenia. Studies conducted through the use of FST and methods based on SFS failed to find convincing signals of positive selection on the CGC-type of the ST8SIA2 gene, another gene that is associated with schizophrenia. A social brain refers to the higher cognitive and affective systems of the brain, evolving as a result of social selection and serving as the basis for social interaction; it is the basis of the complexity of social interactions of which humans are capable. Mechanisms comprising the social brain include emotional processing, theory of mind, self-referencing, prospection and working memory. Patients display defects in various regions of the social brain, such as an inability to grasp social goals, which serves as an indication of a defect in theory of mind. This defect can be caused by the rapid selection for genes associated with language and cognitive ability within the human species. These rapid evolutionary changes, in some cases, may impede normal development within the social brain. As schizophrenia is foremost a disorder of the consciousness, it has been suggested that schizophrenia exists as an unwanted byproduct of the evolution of the prefrontal cortex and other brain regions constituting the social brain. Under increasingly selective pressure induced by increasingly complex social living, the regions of the brain have grown as a means of accommodation and in turn have given rise to vulnerable neural systems. One hypothesis suggests this vulnerability in neural systems has made it possible for changes in genes associated with the social brain that affect neurogenesis, neuronal migration, arborisation, or apoptosis. Although it is unclear which of these factors have exhibited gene changes, it is likely that these changes have contributed to the defect in neurodevelopment seen in schizophrenia patients. A second hypothesis suggests that disturbance in the brain’s frontal circuits, a region that largely constitutes the social brain, can lead to a lack of regulation in cognitive control and processing. This defect in regulation could increase the susceptibility for a social disorder like schizophrenia. This hypothesis refers to the worship of psychics and seers in the times of early civilization; the hallucinatory behavior and delusions brought by schizophrenia may have been highly regaled and allowed the individual to be conferred the title of saint or prophet, raising him on the social spectrum and allowing for social selection to act on the behalf of the disorder. This hypothesis lacks evidence and has not aided in explaining the continued persistence of schizophrenia in modern-day society where people showing symptoms of schizophrenia are typically not identified as saints or prophets. This hypothesis maintains that schizophrenics possess a physiological advantage in the form of disease or infection resistance, a theory that has found basis in diseases such as sickle-cell anemia. In one particular study, NAD, an energy carrier found in animals and yeast, is found to be capable of diminishing infectivity of tuberculosis when present in large quantities; this is done by repressing gene expression. However, M. tuberculosis bacterium has been shown to be capable of acting as a drain on NAD supply. Studies in kynurenine pathway activation reveal that M. tuberculosis infection of the pathway causes niacin receptors in the pathway to indicate high levels of niacin, a precursor to NAD that makes de novo synthesis of NAD from tryptophan unnecessary. This change creates the illusion that NAD levels are adequate and that tryptophan conversion is unnecessary. Coevolution with M. tuberculosis has resulted in an attempt to overcome this illusion in a variety of manners, including the up-regulation of niacin receptors and up-regulation of de novo synthesis of NAD from tryptophan via the kynurenine pathway.