The Impact of Stress and Trauma on White Matter Integrity and Psychotic-like Experiences

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Project Summary/Abstract Individuals with schizophrenia and related disorders experience significant distress related to psychotic symptoms, cognitive deficits, and poor functional outcomes, which represent a large personal and public health burden. White matter (WM) abnormalities have been found across the psychosis spectrum: from those with schizophrenia to non-help-seeking individuals with psychotic-like experiences (PLEs; subclinical, attenuated version of positive psychotic symptoms). WM dysfunction has also been associated with deficits in neurocognition, social cognition, and functional outcome within individuals with psychosis spectrum disorders. As such, identifying contributors to WM dysfunction prior to the onset of psychosis is crucial for early identification and preventing conversion to more severe forms of psychotic illness. Recent studies have found associations between prolonged stress response and WM integrity in individuals with schizophrenia, as well as correlations between early life trauma and WM integrity in animals and individuals with post-traumatic stress disorder; however, psychosocial correlates of WM dysfunction have not yet been identified in individuals experiencing PLEs. The proposed study will utilize diffusion weighted imaging (DWI) within a non-help-seeking community sample of 16 – 24 year olds experiencing a range of PLEs to examine the contribution of psychosocial stress and traumatic life events to the relationship between WM abnormalities and PLEs, and examine the contribution of sex and subtype of PLE to these relationships. This study represents an important step toward identifying causal mechanisms for WM dysfunction within individuals with psychosis spectrum disorders, as well as delineating important targets for interventions. This fellowship would allow me to obtain additional training opportunities, particularly in neuroimaging analysis, which are beyond the scope of my program and I would not otherwise have the time to receive without my own line of funding. My sponsors and I have designed a training plan that will allow me to learn neuroimaging analysis, gain additional expertise in the realms of psychosis and the general effects of stress, learn statistical processing methods needed for my dissertation project, and gain the skills necessary for my future career as an independent investigator. The support of this fellowship will allow me to round out my education and develop into a productive and impactful researcher, identifying causal mechanisms for psychosis spectrum disorders.