Differential Association of the DISC1 Interactome in Hallucinations and Delusions

Multiple genes within the DISC1 (Disrupted-in-Schizophrenia-1) interactome have been implicated in psychotic disorders, which are characterized by hallucinations, delusions, negative symptoms, and disorganized behavior. However, the genetic associations of specific psychotic symptoms remain poorly understood.

We conducted a genetic association analysis of the DISC1 interactome for hallucinations and delusions in schizophrenia and bipolar disorder, using single-nucleotide polymorphism (SNP), gene, and gene-set approaches.

Our findings showed an association between the SNP rs6754640 in the NRXN1 gene and auditory hallucinations. Additionally, rs10263196 (EXOC4), rs7076156 (ZNF365), and nine NRXN1 SNPs were associated with delusions of reference, while rs17039676 (NRXN1) was linked to persecutory delusions. At the gene level, NRG1 and PCM1 were related to auditory hallucinations. The NRXN1, APP, EXOC4, and NUP210 genes were associated with delusions of reference, whereas NRG1 and APP were linked to persecutory delusions. Gene-set analysis indicated that pathways related to the regulation of neuronal structure and function were involved in auditory hallucinations, while cellular transport regulation pathways were associated with persecutory delusions.

This study emphasizes the polygenic architecture of psychosis and suggests that distinct molecular mechanisms contribute to different types of hallucinations and delusions.