Thesis Title: Mapping Genetic Risk for Schizophrenia onto the Triple Network across Adolescent Development: A Longitudinal<\/p>\n
By: Kader Kubat<\/p>\n
Advisor: Timothea Toulopoulou
\nCo-Advisor: Evangelos Vassos<\/p>\n
Date: Sep 4, 2025
\nTime: 03:00 PM Istanbul
\nPlace: Zoom (Online)<\/p>\n
This is an online seminar. To request event details please send a message to department.<\/p>\n
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\u2013SN, DMN\u2013SN, and DMN\u2013FPN connectivity. Specifically, PRS related enhancements were observed in the connections between left LPFC\u2013left SMG, left PPC\u2013right RPFC, right PPC\u2013right SMG, left anterior insula\u2013left LP, left PPC\u2013left PCC, and right PPC\u2013right PCC. None of these PRS modulated connectivity changes, however, were significantly associated with changes in CAPE 42 subclinical symptom scores. The PRS SCZ\u2013related 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.
\nKeywords: Triple Network Model, Resting\u2010state fMRI, ROI to ROI Functional Connectivity, Longitudinal Study, Schizophrenia Polygenic Risk Score, Subclinical Psychotic Symptoms<\/p>\n
Tez Ba\u015fl\u0131\u011f\u0131: \u015eizofreni Genetik Riskinin Adolesan Geli\u015fimi Boyunca \u00dc\u00e7l\u00fc A\u011f Modeline Yans\u0131t\u0131lmas\u0131: Bir Boylamsal \u00c7al\u0131\u015fma<\/p>\n
\u00d6zet: \u00c7ok say\u0131da \u00e7al\u0131\u015fma, \u00dc\u00e7l\u00fc A\u011f Modeli’nin \u015fizofrenideki \u00f6nemini ortaya koymu\u015ftur; ancak sa\u011fl\u0131kl\u0131 ergenlerde bu \u00fc\u00e7 a\u011f aras\u0131ndaki a\u011flar aras\u0131 ba\u011flant\u0131y\u0131 boylamsal olarak inceleyen bir \u00e7al\u0131\u015fma hen\u00fcz yap\u0131lmam\u0131\u015ft\u0131r. Bu bo\u015flu\u011fu doldurmak amac\u0131yla, normal geli\u015fim s\u0131ras\u0131nda a\u011flar aras\u0131 i\u015flevsel ba\u011flant\u0131 de\u011fi\u015fimlerini bir y\u0131ll\u0131k s\u00fcrede ara\u015ft\u0131rt\u0131k ve \u015fizofreniye genetik yatk\u0131nl\u0131\u011f\u0131n (PRS SCZ) bu de\u011fi\u015fimleri nas\u0131l etkiledi\u011fini inceledik. Tezde, 89 ikiz ve karde\u015f \u00e7ifti bir y\u0131ll\u0131k aral\u0131kla i\u015fe dahil edildi ve her iki zaman noktas\u0131nda da dinlenim durumu fMRI \u00e7ekimleri yap\u0131ld\u0131; her oturum i\u00e7in ROI ROI y\u00f6ntemiyle i\u015flevsel ba\u011flant\u0131 de\u011ferleri ayr\u0131 ayr\u0131 hesapland\u0131. Kat\u0131l\u0131mc\u0131lar ayr\u0131ca alt klinik psikotik semptomlar\u0131 de\u011ferlendirmek \u00fczere CAPE 42’yi tamamlad\u0131 ve genotipleme i\u00e7in kan ya da t\u00fck\u00fcr\u00fck \u00f6rnekleri vererek \u015fizofreni poligenik risk skorlar\u0131 (PRS SCZ) elde edildi. Do\u011frusal kar\u0131\u015f\u0131k etkiler modelleri kullan\u0131larak (1) anlaml\u0131 bir boylamsal ba\u011flant\u0131 de\u011fi\u015fikli\u011fi olup olmad\u0131\u011f\u0131, (2) PRS SCZ’nin bu de\u011fi\u015fimleri nas\u0131l etkiledi\u011fi ve (3) ba\u011flant\u0131 de\u011fi\u015fikliklerinin CAPE 42 skoru (toplam, pozitif, negatif, depresif) ile ili\u015fkisi de\u011ferlendirildi. Sonu\u00e7 olarak, ba\u015flang\u0131\u00e7 ve bir y\u0131ll\u0131k takip aras\u0131nda anlaml\u0131 bir zaman etkisi bulunmad\u0131; ancak PRS SCZ, FPN\u2013SN, DMN\u2013SN ve DMN\u2013FPN ba\u011flant\u0131lar\u0131ndaki de\u011fi\u015fim yollar\u0131n\u0131 anlaml\u0131 bi\u00e7imde de\u011fi\u015ftirdi; y\u00fcksek PRS SCZ, bu a\u011flardaki daha b\u00fcy\u00fck art\u0131\u015flarla ili\u015fkiliydi. \u00d6zellikle, y\u00fcksek PRS SCZ’li bireylerde sol LPFC\u2013sol SMG, sol PPC\u2013sa\u011f RPFC, sa\u011f PPC\u2013sa\u011f SMG, sol \u00f6n insula\u2013sol LP, sol PPC\u2013sol PCC ve sa\u011f PPC\u2013sa\u011f PCC ba\u011flant\u0131lar\u0131nda art\u0131\u015f g\u00f6zlendi. Bu PRS SCZ mod\u00fclasyonlu ba\u011flant\u0131 de\u011fi\u015fiklikleri ise CAPE 42 alt klinik semptom skorlar\u0131 ile anlaml\u0131 bir ili\u015fki g\u00f6stermedi. PRS SCZ’ye ba\u011fl\u0131 bu ba\u011flant\u0131 art\u0131\u015flar\u0131, hasta ve y\u00fcksek riskli gruplarda g\u00f6zlenen \u00f6r\u00fcnt\u00fclerle paralellik ta\u015f\u0131yarak semptomlar ortaya \u00e7\u0131kmadan \u00f6nce \u015fizofreni patolojisinin erken n\u00f6rogeli\u015fimsel mekanizmalar\u0131na i\u015faret ediyor olabilir. Bu bulgular, PRS SCZ’nin \u015fizofreni riskine y\u00f6nelik erken bir biyobelirte\u00e7 potansiyeline sahip oldu\u011funu vurgularken, do\u011frusal olmayan geli\u015fimsel izlerin ortaya konmas\u0131 i\u00e7in daha uzun s\u00fcreli boylamsal \u00e7al\u0131\u015fmalar\u0131n gereklili\u011fini ortaya koymaktad\u0131r. Anahtar Kelimeler: \u00dc\u00e7l\u00fc A\u011f Modeli, Dinlenim Durumu fMRI, ROI ROI Fonksiyonel Ba\u011flant\u0131, Boylamsal \u00c7al\u0131\u015fma, \u015eizofreni Poligenik Risk Skoru, Subklinik Psikotik Semptomlarm<\/p>\n","protected":false},"excerpt":{"rendered":"
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 [\u2026] <\/p>\n