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    Differential Selection and Schizophrenia Orthologues: The Roles of Life History, Neuroanatomy, and Socioecology

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    Author
    Penaherrera Aguirre, Mateo
    Issue Date
    2020
    Keywords
    Comparative Evolutionary Psychology
    Non-Human Species
    Orthologues
    Phylogenetic Methods
    Psychopathology
    Schizophrenia
    Advisor
    Jacobs, William J.
    
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    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The evolution of major psychopathologies remains a point of intense debate within the scientific community. Counter to classical Darwinian perspectives, these disorders persist in human populations despite their high fitness costs (shorter lifespan and fewer surviving offspring reaching sexual maturity). Schizophrenia, an umbrella term referring to a cluster of positive (delusions, hallucinations, disorganized behaviors) and negative signs (flattened affect, limited motility, anhedonia, asociality, among others), is no exception. Over the past three decades, researchers have developed various theories to address this evolutionary conundrum. Comparative researchers have addressed this subject by investigating numerous empirically based animal models. These investigations have detected potential mechanisms involved in the development of schizophrenia and explored the effectiveness of various interventions aimed towards reducing the pathology’s severity. Even though this approach offers a unique approach to this subject, the current literature could benefit from a comparative phylogenetic perspective. For example, the molecular genetic literature has identified a positive association between life history indicators, such as maximum longevity, with the persistence of ancestral variants of genes (orthologues) across non-human species. Given that slow-life history species are generally subject to weaker selective pressures, this pattern is expected. Hence, deleterious or near deleterious mutations are harder to eliminate. The present dissertation aims to complement the molecular genetic literature by considering the roles of life history, neuroanatomy, and socioecology in this pathology's evolution. The current manuscript describes three comparative phylogenetic studies that outline the evolution of schizophrenia. Study 1 explored the connection between life history and the (dN) ̅⁄(dS) ̅ values (a metric of orthologue persistence) of this pathology. Building on the previous result, Study 2 proposed a comparative phylogenetic examination of schizophrenia, autism, and bipolar disorder orthologues, as a potential complementary avenue for understanding the evolutionary dynamics of comorbidity among these disorders. As predicted, the analyses detected an underlying common genetic factor loading into the orthologue estimates for each disorder. Moreover, a Higher-Order Life History factor exhibited significant positive associations with the (dN) ̅⁄(dS) ̅ values of autism and bipolar disorder. Similarly, this latent variable positively and significantly predicted the Genetic Psychopathology factor. Study 3 explored the connections among substrate use, diet, sociality, life history, neuroanatomy, and their respective relations with the persistence of schizophrenia orthologues in eutherian mammals. The model hypothesized that a Higher-Order Life History factor should positively associate with neuroanatomical indicators such as the species’ total number of neurons. Lastly, the number of neurons predicted the persistence of schizophrenia orthologues. Life history mediated the association between sociality and neuroanatomy. Moreover, the total number of neurons mediated the connection between life history and the estimates for schizophrenia orthologues. The phylogenetic model demonstrated that sociality, a Higher-Order Life History, and the total number of neurons had significant positive associations with schizophrenia ancestral alleles' persistence.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Psychology
    Degree Grantor
    University of Arizona
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