Disrupted Associations between the Transcriptome Profile, Brain Structure and Function, and Cognitive Ability in Schizophrenia

Cognitive dysfunction is considered to be one of the core symptom dimensions of schizophrenia. To deconstruct the underlying etiological behind cognitive deficits from a more integrated and multidimensional perspective, we established a trans-scale dataset at the level of the individual corresponding to each participant and control, containing blood-sample transcriptome profile, neuroimaging endophenotypes, and cognitive ability. Multivariate correlation analysis and mediation analysis demonstrated that the gene-brain-cognition associations were exsisted in healthy controls, whereas disrupted in patients with schizophrenia. These results provide a preliminary clue in comprehending the misaligned relationship between the microscale biological pathways and macroscopic phenotypes in schizophrenia.