Cognitive functioning in schizophrenia: Characterising the effects of common genetic variation, brain structure, inflammation, and early life adversity
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2024-03-08Author
Corley, Emma
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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.