"Biopsychosocial Markers of Social Adversity as Risk Factors for Mental" by Meghan Alexandra Collins

Date of Award

Fall 2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Advisor

Cannon, Tyrone

Abstract

Stress and adversity are strong predictors of poor mental health outcomes among individuals at clinical high-risk for psychosis (CHR). Furthermore, atypical neurodevelopment during adolescence has been proposed as a biological mechanism that contributes to psychosis onset. Approximately 20% of youth who meet CHR criteria will go on to develop a psychotic disorder within two years. Thus, delineating the mechanisms linking adversity and neurodevelopment with conversion to psychosis is important for enhanced risk identification and early intervention. There is a lack of clarity in the existing literature regarding which types of adversity are most predictive of poor clinical outcomes among CHR, and if there is specificity in pathways between different forms of adversity, brain regions and/or neuromaturational processes most impacted, and clinical outcomes. Additionally, studies to-date have not empirically established the timeframe across which neurodevelopmental changes are observable in the ramp up to psychotic illness, nor have they confirmed that shifts in brain structure are observable prior to psychotic illness onset. Thus, the timeframe across which adversity may impact active brain and behavioral illness markers during the period of acute risk for psychosis is currently unknown. The studies in this dissertation are designed to elucidate the effects of various forms of social adversity on brain structural development and clinical outcomes among CHR adolescents and young adults. Empirical work presented in this dissertation further emphasizes early risk prediction by focusing on longitudinal investigations designed to clarify the timescale of neurodevelopmental changes related to adversity and clinical outcomes. Following a general introduction (Chapter 1), Chapter 2 presents the first longitudinal investigation of brain structural changes that precede the onset of psychosis, among a large sample of CHR and healthy control (HC) adolescents and young adults in the third wave of the North American Prodrome Longitudinal Study (NAPLS3). Results indicate that accelerated cortical thinning in multiple prefrontal, temporal, and parietal areas is observable among CHR who convert to psychosis, relative to CHR non-converters and HC. Results further demonstrate that thinning in these regions across less than 3 months, on average, reliably predicts whether a CHR individual will ultimately convert to psychosis. This chapter provides critical evidence for the utility of high-frequency assessments of brain structural change as a tool for early risk prediction among CHR, and thus provides a foundation for Chapters 3 and 4. Chapter 3 considers a range of environmental risk variables related to social adversity and employs data-driven factor analysis to define types of social adversity that are most predictive of specific symptom outcomes and neurodevelopmental changes across short intervals among participants in NAPLS3. Results indicate that social adversity can be characterized by six factors—childhood maltreatment/abuse, stress and poor coping, poor social support, bullying/peer rejection, poor school achievement, and socioeconomic disadvantage. Across CHR and HC, childhood maltreatment/abuse is associated with a less steep rate of cortical thinning in left medial superior frontal cortex, whereas socioeconomic disadvantage is associated with lower volume in the hippocampus, amygdala, nucleus accumbens, and caudate, and higher left lateral ventricle volume across the period of study. Poor social support, bullying/peer rejection, and poor school achievement were each associated with several baseline symptoms. Chapter 4 provides the first known longitudinal investigation directly assessing the mechanistic role of cortical thinning in relationships between social adversity and clinical outcomes among CHR individuals. This study focuses on discriminatory experiences, a key form of adversity known to increase risk for psychosis and thought to partially explain higher psychotic illness rates among minoritized individuals. Results indicate that discriminatory experiences are associated with lower cortical thickness across time in broad aspects of frontal and temporal cortex. Furthermore, thickness in these regions partially mediates links between discrimination and later symptoms of anxiety, but not positive symptoms of psychosis, among CHR and HC. Overall, the studies in this dissertation suggest that changes in brain structure across short time increments are reliable early risk predictors of psychotic illness onset and other poor outcomes among adolescents and young adults. Results suggest that aspects of adversity differentially impact neurodevelopment and clinical outcomes and provide evidence that brain structural change is a mechanism through which certain forms of adversity (i.e., discrimination) impact later symptoms. Though these studies examine CHR youth and their HC counterparts, implications for other clinical and non-clinical populations are discussed (Chapter 5). Findings of this dissertation have important implications in considering interventions and policy initiatives geared towards reducing social adversity, and in considering treatments directed towards mechanisms involved in psychosis-related brain structural shifts.

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