Abstract
Genetic risk is thought to drive phenotypic variation on a spectrum of schizophrenia-like social and cognitive personality traits; but the intermediate phenotype of brain structural variation that mechanistically links sequence variation to schizotypal experience and behavior is unclear. We assessed schizotypy through a self-reported questionnaire, and measured magnetization transfer (MT), as a putative MRI marker of intra-cortical myelination, in 68 brain regions, in 248 healthy young people (aged 14-25 years). We found that magnetization was positively correlated with schizotypy scores in bilateral regions of posterior cingulate cortex and precuneus (FDR-corrected P < 0.05). Meta-analysis of prior normative functional MRI data indicated that this area of schizotypy-related magnetization is specialized for memory and social cognitive functions that are impaired in schizophrenia. Using prior data from case-control studies of human brain gene transcription post mortem, we found that schizotypy-related magnetization was significantly correlated with transcriptional dysregulation in schizophrenia. The proteins coded by genes that were both positively weighted on schizotypy-related magnetization and significantly down-regulated in schizophrenia formed a dense, complex network of interactions for neuronal signaling. We conclude that intra-cortical magnetization - putatively a marker of myelinated neurons - is a plausible brain phenotype of schizotypy and represents some genetic risks for schizophrenia.
Footnotes
↵‡ Full member list available in Supplementary Materials