Advisory Committee Chair
Nina Kraguljac
Advisory Committee Members
David Knight
Gerhard Hellemann
Jarred Younger
Junghee Lee
Document Type
Dissertation
Date of Award
1-1-2025
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
Schizophrenia is highly heterogeneous in its neurobiological and clinical presentations, which hinders attempts to understand its pathophysiology, limits efforts to identify biomarkers, and deters optimal patient care. A way to parse clinical heterogeneity is to subtype patients based on clinical presentations. The deficit syndrome (DS) is a possible subtype, characterized by primary and enduring negative symptoms. Evidence for neurobiological abnormalities dissociating DS from other forms of schizophrenia is inconsistent as most studies do not account for heterogeneity within patient groups due to limitations of group-level comparisons. The question remains whether DS presents a unique and less heterogeneous neurobiological phenotype. The goals of this work are to (1) systematically review the literature on magnetic resonance imaging studies of DS, (2) to test deficit/non-deficit (NDS) distinctions in the functional connectome, and (3) to parse clinical and neurobiological heterogeneity among first-episode psychosis (FEP) patients with and without features of DS. Therefore, we used graph theory to characterize group-level differences in the functional connectome. We hypothesized that functional network segregation would be lower in clinical subgroups compared to healthy controls (HCs), and that functional network integration, would be higher in FEP-DS compared to FEP-NDS, and HCs. Furthermore, we used normative modeling to assess individual-level abnormalities, enabling us to capture inter-individual variability and to dissect neurobiological heterogeneity. We hypothesized that FEP-DS patients would be less heterogeneous in individual-level structural and functional abnormalities, compared to FEP-NDS. Graph theory group-level analyses revealed that only FEP-DS patients had lower integration and segregation in the functional connectome, compared to HCs. Normative modeling analyses showed that, at the individual level, FEP-DS and FEP-NDS patients were not different in abnormalities of cortical thickness and resting-state functional connectivity. Importantly, FEP-DS patients showed similar neurobiological heterogeneity compared to FEP-NDS. This challenges the idea that DS is a more homogeneous subtype of schizophrenia which, so far, has only been tested in group-level comparisons. Normative models are useful for capturing inter-individual variability in schizophrenia, which can help to determine whether clinical subgroups differ in neurobiological heterogeneity. Defining neurobiologically more homogeneous subgroups may lead to clinically useful applications, such as tailored treatments with better treatment responses.
Recommended Citation
Teles Gomes De Araujo, Matheus, "Parsing Clinical And Neurobiological Heterogeneity In First-Episode Psychosis Patients With And Without Features Of The Deficit Syndrome Of Schizophrenia" (2025). All ETDs from UAB. 6894.
https://digitalcommons.library.uab.edu/etd-collection/6894
Comments
etdadmin_upload_1140994