Thickness and Surface Area Difference in Schizophrenia Stratified by Duration of Illness in the GENUS Dataset

Victor Zeng, BS

Beth Israel Deaconess Medical Center
Thickness and Surface Area Difference in Schizophrenia Stratified by Duration of Illness in the GENUS Dataset

Scientific Abstract

Background: Schizophrenia (SZ) is a serious mental disorder with complex and diverse symptomatology. Abnormalities of several brain regions have been identified; nonetheless, the neural mechanisms underlying psychosis are largely unknown. Here, utilizing the large, deeply phenotyped GENUS dataset, we investigate CT and SA in relation to duration of illness in subjects affected by schizophrenia. We predicted that morphometric abnormalities of global CT and SA and of language/attention regions will be associated to illness duration when controlling for aging effects, with CT as the stronger direct correlate for duration of illness.

Methods: Subjects were: Familial high risk (FHR, n=329); SZ: Early Course < 3 years from first hospitalization (EC, n=346), Middle > 3 years < 10 years (MC, n=216), and Chronic course > 10 years (CC, n=378); and controls (HC) (n=1313). T1-MPRAGE scans were processed using FreeSurfer 5.3 and total mean CT and total SA measurements, as well as CT and SA for the following regions: the banks of superior temporal sulcus, the middle temporal, the fusiform, the Heschl, the inferior parietal, the supramarginal, the pars opercularis, and the pars triangularis. Probands-control comparisons were carried out after propensity matching on age, sex, race, and effect sizes of group comparisons (pfdr<0.05) are false discovery rate corrected.

Results: The EC, MC, and CC groups had diminished global CT and SA (pfdr<0.05, -d= -0.16 to -0.47) compared to controls. Only CT, but not SA, distinguished SZ from FHR. Effect sizes for SZ CT difference with HC were increasingly stronger from EC to MC to CC, for both global CT and CT of language/attention network regions.

Discussion: We identify and confirm CT as the main brain measure affected across different stages of SZ. We also determine that thinner CT present in the early course of the illness continues to thin with illness duration, significantly widening the gap with age matched controls, indicating both neurodevelopmental but also neurodegenerative processes at play during the course of the illness.

research Areas

Authors

Victor Zeng, BS, Joyce Zhou, Evie Coxon, Nicole Rychagov, Gabriella Blokland, PhD, Matcheri Keshavan, MD, Elisabetta C. del Re, PhD

Principal Investigator

Matcheri Keshavan, MD, Elisabetta C. del Re, PhD