Formal thought disorder and familial risk in first-episode psychosis: A study of cortical thickness and neuroimaging-transcriptomic association analysis

Formal thought disorder (FTD), a prominent feature of schizophrenia, encompasses disruptions in thought, language, and communication. This study examines cortical thickness (CT) alterations in first-episode psychosis (FEP) patients (N = 24), their siblings (SIB) (N = 21), and healthy controls (CON) (N = 21) to explore potential neural correlates of FTD. Using structural MRI, we analyzed whole-brain CT and its relationship with positive and negative FTD measured by Thought and Language Index. Out-of-sample spatial correlations of gene expression with regional CT were also performed using a transcriptomic dataset. FEP had significant CT reductions in right middle frontal gyrus (MFG) compared with SIB and CON and in superior frontal gyrus (SFG) compared to CON; but SIB did not differ from CON. GLM analyses demonstrated that negative FTD exerted a significant main effect on CT in the MFG and SFG. By contrast, positive FTD showed no significant associations with CT. Neuroimaging-transcriptomic association analysis identified key biological pathways linked to cortical morphology. These findings emphasize the specific association between negative FTD and CT alterations in frontal brain regions, confirming prior reports. Future research should examine larger cohorts and investigate additional FTD subtypes to further elucidate neural correlates and potential familial risks of schizophrenia.