Cognitive functioning in schizophrenia: Characterising the effects of common genetic variation, brain structure, inflammation, and early life adversity
Corley, Emma
Corley, Emma
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Publication Date
2024-03-08
Type
Thesis
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Abstract
Schizophrenia is a complex, highly polygenic neuropsychiatric disorder. Individuals with schizophrenia experience neurocognitive and social cognitive deficits that can impact their ability to work, live independently, and form relationships. These deficits are associated with several common genetic risk variants for schizophrenia and may be exacerbated by environmental factors such as childhood trauma. Increasing evidence suggests a role for the involvement of inflammation in mediating the genetic and environmental risk for schizophrenia. A current gap in knowledge is how such genetic, biological, and environmental factors combine and interact to explain variability in cognitive functioning in patients with schizophrenia. Investigating these neurobiological mechanisms as well as considering environmental effects that confer greater susceptibility to deficits in cognition is needed to clarify how best to target these deficits and to improve treatment development, implementation, and outcomes. This thesis examines the relationship between genetics, early life adversity, and cognitive functioning in both individuals with schizophrenia and healthy participants. It also explores the role of immune and neural mechanisms behind these relationships. The four studies presented in this thesis demonstrate that exposure to early life adversity is associated with both social and neurocognitive functioning in patients with schizophrenia and healthy participants. Furthermore, the results show that proinflammatory cytokines and white matter microstructural organization mediate the association between early life adversity and cognitive ability. While the genetic liability for schizophrenia contributes to cognitive impairments in both patients and healthy controls, it has a modest effect. Overall, the findings from this thesis support the neurodevelopmental and immune hypotheses of schizophrenia and emphasise the need to target cognitive impairments and develop new strategies to mitigate the impact of adverse life experiences on brain structure in both clinical and nonclinical populations.
Publisher
NUI Galway