Şizofreni genetik riskinin adolesan gelişimi boyunca üçlü ağ modeline haritalanması: Boylamsal bir çalışma

The Triple Network Model, which includes the Default Mode Network (DMN), Frontoparietal Network (FPN), and Salience Network (SN), is a core model for schizophrenia and explains all the positive, negative, and cognitive symptoms. Many studies demonstrated the importance of the Triple Network Model in schizophrenia; however, no longitudinal study has yet examined the 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 subclinical psychotic symptom 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 lateral prefrontal cortex (LPFC)–left supramarginal gyrus (SMG), left posterior parietal cortex (PPC)–right rostral prefrontal cortex (RPFC), right PPC–right SMG, left anterior insula (AI)–left lateral parietal cortex (LP), left PPC–left posterior cingultae cortex (PCC), and right PPC–right PCC. None of these PRS‑modulated connectivity changes, however, were significantly associated with changes in 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 the potential of Triple Network Model functional connectivity as an early biomarker of schizophrenia risk and underscore the need for extended longitudinal follow‑up to capture non‑linear developmental trajectories.