Thesis Title: Mapping Genetic Risk for Schizophrenia onto the Triple Network across Adolescent Development: A Longitudinal
By: Kader Kubat
Advisor: Timothea Toulopoulou
Co-Advisor: Evangelos Vassos
Date: Sep 4, 2025
Time: 03:00 PM Istanbul
Place: Zoom (Online)
This is an online seminar. To request event details please send a message to department.
Abstract: Many studies have demonstrated the importance of the Triple Network Model in schizophrenia; however, no longitudinal study has yet examined between network connectivity among the three Triple Network systems in healthy adolescents. To address this gap, we conducted a one year investigation of between network functional connectivity during typical development and assessed how genetic liability to schizophrenia moderates these changes. In this thesis, 89 pairs of twins and siblings were recruited and underwent resting state fMRI at baseline and one year follow up, with ROI to ROI functional connectivity values computed separately for each session. Participants also completed the CAPE 42 to assess subclinical psychotic symptoms and provided blood or saliva samples for genotyping to derive schizophrenia polygenic risk scores (PRS SCZ). Using linear mixed effects models, we evaluated (1) whether significant longitudinal connectivity changes occurred, (2) whether PRS SCZ moderated these longitudinal changes, and (3) whether connectivity changes were associated with CAPE 42 scores (total, positive, negative, and depressive). We found no significant time effect from baseline to follow up; however, PRS SCZ significantly moderated connectivity trajectories, with higher PRS SCZ associated with greater increases in FPN–SN, DMN–SN, and DMN–FPN connectivity. Specifically, PRS related enhancements were observed in the connections between left LPFC–left SMG, left PPC–right RPFC, right PPC–right SMG, left anterior insula–left LP, left PPC–left PCC, and right PPC–right PCC. None of these PRS modulated connectivity changes, however, were significantly associated with changes in CAPE 42 subclinical symptom scores. The PRS SCZ–related connectivity increases paralleled patterns observed in patients and other high risk groups, suggesting that these alterations may reflect early neurodevelopmental mechanisms underlying schizophrenia pathology before the emergence of clinical symptoms. These findings highlight PRS SCZ’s potential as an early biomarker of schizophrenia risk and underscore the need for extended longitudinal follow up to capture non linear developmental trajectories.
Keywords: Triple Network Model, Resting‐state fMRI, ROI to ROI Functional Connectivity, Longitudinal Study, Schizophrenia Polygenic Risk Score, Subclinical Psychotic Symptoms