Establishing Interhemispheric Interaction assessed by resting state fMRI as an Intermediate Phenotype of Schizophrenia Risk Genes

• Applicant: Professorin Dr. Sophia Stöcklein
• Subject Area: Biological Psychiatry
• Term: Funded in 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 212170118

Genetic factors account for more than 80% of the variance in schizophrenia susceptibility, therefore understanding the genetic underpinning is crucial for developing new treatment strategies. Imaging genetics, which uses brain activity patterns as intermediate phenotypes, provides a unique tool to investigate the impact of polymorphisms on brain function. These intermediate phenotypes are suggested to be closer to the genetic substrate than are heterogeneous clinical symptoms. We propose to establish a new intermediate phenotype based on interhemispheric interaction that leads to brain lateralization. Imaging studies consistently demonstrated that schizophrenia is associated with altered lateralization which is further correlated with the symptom severity. Our groups preliminary data indicate that functional laterality could be unraveled by hemispheric interaction measured by resting state fMRI. The overall aim of this project is to construct a task-independent imaging biomarker based on intrinsic hemispheric interaction, which could serve as an intermediate phenotype of schizophrenia risk genes.Aim 1: Develop an image score based on intrinsic hemispheric interaction in a patient/control cohort. Aim 2: Demonstrate genetic underpinnings of the proposed imaging biomarker.Subaim 2A: Compute a polygenetic score that best predicts the imaging score in 2000 healthy control subjects.Subaim 2B: Test the polygenetic risk score in an independent patient/control cohort to determine its association with pathology.The result of this project will be a reliable and widely applicable intermediate phenotype for schizophrenia risk genes that can be rapidly acquired in large cohorts of subjects without task constraints such as language capacity and task compliance. We also anticipate that this task-independent imaging biomarker will provide greater statistical power in genetic association studies than traditional task induced activation.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Randy L. Buckner