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Thirty-Third Annual Meeting of the Society for Research in Psychopathology

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124. Developmental Neurogenetics of Cortical Thickness and Cortical Surface Area in Schizophrenia: A Multiplex Extended Pedigree Study

Schizophrenia genetic effects on neurodevelopment may remain stable from childhood (as proposed by early neurodevelopmental models) or increase during adulthood, closer to the peak age-of-onset (as proposed by late neurodevelopmental models). To examine whether the genetic correlation between schizophrenia and brain morphology changes across peak age-of-onset, 230 relatives from 32 multiplex, extended pedigrees and 276 unrelated controls underwent MRI scanning and were stratified based on their ages relative to schizophrenia age-of-onset, which peaks at approximately 23 years and plateaus at 42 years (age groups: 12-22, 23-42, 43-84). Genetic analyses revealed that the genetic correlation between schizophrenia and total cortical surface area was high before peak age-of-onset (Rg=-0.839), decreased (p=.002) after peak age-of-onset (Rg=-0.636), and further declined during plateau age-of-onset (Rg=-0.354). However, the genetic correlation between schizophrenia and mean cortical thickness was low before peak age-of-onset (Rg=0.108), increased (p<.001) after peak age-of-onset (Rg=-0.360), then declined afterwards (Rg=-0.092). Overall, schizophrenia genetic effects influence cortical surface area more before peak age-of-onset and cortical thickness after peak age-of-onset. Our findings suggest that the effects of schizophrenia genetic risk influence different aspects of brain structure before and after schizophrenia age-of-onset, emphasizing the importance of examining whether schizophrenia genetic risk variants change expression similarly across neurodevelopment.

Susan Kuo
University of Pittsburgh

David Roalf
University of Pennsylvania

Konasale Prasad
University of Pittsburgh

Christie Musket
University of Pittsburgh

Petra Rupert
University of Pittsburgh

Joel Wood
University of Pittsburgh

Ruben Gur
University of Pennsylvania

Laura Almasy
University of Pennsylvania

Raquel Gur
University of Pennsylvania

Vishwajit Nimgaonkar
University of Pittsburgh

Michael Pogue-Geile
University of Pittsburgh

 


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