Advisor(s)
Nina Kraguljac
Committee Member(s)
Brandon Pruett
Gerhard Hellemann
Junghee Lee
Kristina Visscher
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Joint Health Sciences
Date of Award
9-11-2025
Abstract
Psychosis is an heterogenous condition that occurs in many psychiatric disorders. It has a variable symptom presentation and recent initiatives have suggested that investigating the underlying neurobiology of psychiatric disorders rather than their symptomatology would provide a more accurate picture for diagnosis, prognosis, and treatment. Grey matter has been implicated in the pathophysiology of psychosis and psychotic disorders, though significant natural variation due to age and sex have impeded the distinction of pathologically relevant grey matter abnormalities in psychosis. Additionally, case-control approaches to exploring grey matter abnormalities in psychotic disorders often obscure subtle variation in individuals. Here, we utilize a normative modeling approach to better capture individual variation in early psychosis and psychotic disorders. We investigate clinically observable features of psychotic disorders such as treatment response, cognitive deficits, and diagnostic categories in the context of their grey matter structural deviations to better understand the neurobiological basis for these features. Chapter 1 finds significant subcortical heterogeneity in first episode psychosis patients that is obscured by traditional case-control analysis. Additionally, subcortical deviations in key dopaminergic regions are more closely related to 16-week antipsychotic treatment response than raw subcortical volume. Chapter 2 finds that cognitively intact and impaired first episode psychosis patients are not significantly different from one another, both structurally and functionally. Chapter 3 finds that patients with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features are indistinguishable from one another at the grey matter structural level, with no defining regional abnormalities or patterns of cortical deviation. This body of work suggests that psychotic disorders show higher heterogeneity than previously believed and that clinically observable homogeneity is not always indicative of neurobiological homogeneity. It emphasizes the importance of supplementing case-control analytical approaches with more individualized ones such as normative modeling to better understand the variety of neurobiological presentations in these complex disorders.
ProQuest ID
Recommended Citation
Remiszewski, Natalie, "Understanding Psychotic Disorders Using Normative Modeling-Derived Individual-Level Brain Structural Abnormalities" (2025). All ETDs from UAB. 7401.
https://digitalcommons.library.uab.edu/etd-collection/7401
