Genetic Disorders That Confer Risk for the Development of Psychosis and White Matter Hyperintensities on T2-weighted Imaging: A Practical Guide for Psychiatrists.

OBJECTIVE: A variety of diseases can cause both psychosis and myelin changes that manifest as white matter hyperintensities on T2-weighted magnetic resonance imaging of the brain. Although many of the acquired conditions relevant to this discussion are widely recognized by psychiatrists and other physicians, a number of lesser-known rare genetic disorders also deserve consideration in this context. As such, this review sought to summarize the phenotypic features, brain imaging abnormalities, and approach to diagnosing the most common leukodystrophies and other genetic leukoencephalopathies that can cause psychosis. METHODS: This is a narrative review. The most common leukodystrophies that can cause both psychosis and white matter hyperintensities are first reviewed, followed by a variety of other rarer leukodystrophies and related genetic disorders. Suggestive clinical features, workup recommendations, and potential clinical implications are subsequently discussed. RESULTS: Although the psychotic symptoms that occur in these disorders might phenomenologically resemble those typical of schizophrenia, the identification of any "red flag" neurological features, idiosyncratic medical comorbidities, additional brain imaging abnormalities, parental consanguinity, or a mendelian pattern of inheritance, should prompt consideration for an underlying genetic explanation. Making a correct diagnosis in this context is critical, given the numerous potential clinical implications, including with respect to treatment decisions. CONCLUSION: While psychiatrists are not expected to be experts in this area, at a minimum they should have a basic familiarity with the genetic disorders that are most likely to cause both psychosis and white matter hyperintensities, given the relatively frequent occurrence of this clinical scenario.