PB 22 Association between genetic risk for schizophrenia and deactivation of the right temporo-parietal junction during working memory encoding – An imaging genetics study

Abstract

Introduction Schizophrenia is a complex genetic disorder, whose highly polygenic architecture has only partly been elucidated. Recent genome-wide association studies (GWAS) have provided evidence for a growing number of common genetic risk variants. However, the impact of these risk genes on brain function remain poorly understood. In the current imaging genetics study, we investigated the correlation between brain activation during a visuospatial working memory task and genetic risk for schizophrenia. Methods 98 right-handed individuals without personal or family history of psychiatric disorders underwent fMRI during the performance of a visuospatial change detection task. During encoding, an array of three red rectangular bars, which varied in orientation, was presented for 33 ms. After a delay period, a second array was presented for 3000 ms (retrieval). This array was identical to the first array in 50% of trials. Data analysis in Brain Voyager QX 2.8 included standard data preprocessing and a multiscale curvature driven cortex based alignment procedure to minimize macro-anatomical variability between subjects. Subsequently, functional data were analyzed using a random-effects multi-subject general linear model. Participants were genotyped using a custom Illumina HumanCoreExome-24 BeadChip array. Polygenic scores (PGS) for schizophrenia were calculated based on Psychiatric Genetic Consortium data (PGC2). Results We observed a significant negative correlation between BOLD activation in the right temporo-parietal junction (TPJ) and PGS for schizophrenia during the encoding phase. Closer inspection indicated that the right TPJ – part of the ventral attention network – was reliably deactivated across all particpants during the encoding phase. However, participants with higher PGS showed stronger deactivation. Conclusions Previous studies reported stronger deactivation of the right TPJ during working memory encoding with increasing cognitive demand. Therefore, our results indicate that participants with a higher genetic risk for schizophrenia had to commit more cognitive resources to encode information into working memory. This finding is also well in line with converging evidence for a primary disturbance of working memory encoding in schizophrenia.