Introduction:
Schizophrenia (Sz) patients show impairments of cognitive functions, esp. short-term memory, and also alterations of hippocampal structure and function. However, it is unclear how genetic liability contributes to these effects, since sibling studies are limited. We tested the hypothesis that memory-related hippocampal task-related activation in an encoding paradigm using fMRI would correlate with a polygenic measure of schizphrenia risk. Method: We studied a total of n = 386 healthy subjects (147 men, 239 women, aged 31.4, SD = 11.8 years) from the FOR2107 study while performing an encoding-task using functional MRI at 3 Tesla. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score (PGRS) was calculated for SZ using PGC SZ GWAS results.

Results:
We found a negative correlation of PGR scores with anterior cingulate cortex (ACC) activation. This effect was significant at p = 0.001 uncorrected levels, but did not survive more conservative correction for multiple comparisons with FWE.

Discussion:
Our findings demonstrate the impact of polygenic risk for schizophrenia to modulate memory-related activation in the ACC, a brain structure central to cognitive control in executive and memory functions as well as integration of information. This suggests that nodes of memory-related networks are modulated by genetic liability even in healthy subjects, while hippocampal impairment itself might rely on the expression of the disease phenotype.