The evolution of schizophrenia refers to the theory of natural selection working in favor of the disorder. 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 an unwanted byproduct accompanying desired genes.
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Social brain hypothesis
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. 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, allowing for psychoses such as schizophrenia to appear.
Social advantage hypothesis
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 this idea of saints and prophets has no role.
Physiological advantage hypothesis
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. An enzyme implicated in the initiation of the kynurenine pathway, tryptophan 2,3-dioxygenase (TDO2) is found to activate during niacin-deficient conditions and is also found to be in increased levels in schizophrenic brains. In the postmortem brain tissue of schizophrenics, the protein for the high affinity niacin receptor was significantly decreased and, as a result, would allow for the up-regulation of mRNA transcript for the niacin receptor.
Shamanistic hypothesis
This hypothesis purports that schizophrenia is a vestigial behaviour that was once adaptive to hunting and gathering tribes. Psychosis prompts shamans to communicate with the imaginary spirit world, which results in the formation of religious myths. The shamanistic theory posits that the universal presence of shamanism in all hunting and gathering societies is likely due to heritable factors - the same heritable factors that support the worldwide distribution of schizophrenia. One modern version of the theory has invoked the evolutionary mechanism of group selection in order to explain the apparent genetic-based task specialization of shamanism.