The cooccurrence of psychosis and emergent cognitive impairment/decline in rare genetic disorders: A scoping review

OBJECTIVE: Cognitive impairment is a core feature of schizophrenia, and psychosis can occur in numerous types of dementia. Although rare genetic variation may underlie the development of psychosis or dementia in some individuals, no reviews to date have explored the spectrum of genetic disorders that have the potential to cause both. Given the clinical utility of characterizing the corresponding differential diagnosis, this scoping review sought to identify all rare genetic disorders that plausibly confer risk for both psychosis and cognitive decline. METHODS: This review involved consecutive literature searches using PubMed and Scopus. The first search combined terms related to psychosis, cognitive decline, and genetics, while the second was intended to find any additional articles that described the occurrence of psychotic symptoms among individuals diagnosed with the diseases (and related diseases) identified in the first search. After duplicates were removed, articles that provided individual-specific information pertaining to the development of both psychosis and new-onset cognitive impairment/decline were retained, provided there was no secondary explanation to account for the symptoms. RESULTS: The two searches ultimately yielded 151 and 230 eligible articles, respectively, corresponding to 52 genetic disorders/genetic disorder categories and 90 genes. Although some are well-known to confer risk for both psychosis and dementia, others have only rarely been associated with either. CONCLUSION: This scoping review highlights the diverse array of genetic diseases that have the potential to cause both psychosis and new-onset cognitive impairment/decline. It also lays the groundwork for the completion of disease-specific systematic reviews on this topic.