What familial cancers are genetically associated with psychosis?

From the Guidelines

Familial cancers genetically associated with psychosis include Li-Fraumeni syndrome, Cowden syndrome, Lynch syndrome, and BRCA1/2 mutations, with Li-Fraumeni syndrome being the most notable due to its association with higher rates of psychotic disorders. When considering the genetic association between familial cancers and psychosis, it's essential to examine the most recent and highest quality studies. According to 1, Li-Fraumeni syndrome, caused by mutations in the TP53 gene, not only increases the risk for various cancers but also has been linked to higher rates of psychotic disorders, suggesting a potential shared genetic pathway affecting neurodevelopment and cellular regulation. Some key points to consider in the association between familial cancers and psychosis include:

• Li-Fraumeni syndrome: characterized by a significant psychological burden due to exposure to multiple experiences of grief and threats to personal well-being, as well as a potential link to psychotic disorders 1.
• Cowden syndrome, Lynch syndrome, and BRCA1/2 mutations: although less directly studied in relation to psychosis than Li-Fraumeni syndrome, these syndromes have shown correlations with psychotic symptoms or disorders, indicating a complex interplay between cancer genetics and psychiatric conditions.
• The importance of comprehensive psychiatric assessment alongside cancer screening for individuals with these familial cancer syndromes, as early intervention improves outcomes for both conditions.
• The potential bidirectional relationship between primary psychotic disorders and altered cancer risk profiles, which requires further research to fully understand. Given the current state of evidence, it is crucial for patients with these familial cancer syndromes to receive multidisciplinary care, including psychiatric evaluation and support, to address both their cancer risk and potential psychiatric needs.

From the Research

Familial Cancers and Psychosis

• There is evidence to suggest that certain familial cancers may be genetically associated with psychosis, although the relationship is complex and not fully understood 2.
• A study found that a missense mutation at the MACF1 gene, combined with rare duplications DUP3p26.3 and DUP16q23.3, affecting the CNTN6 and CDH13 genes, was associated with familial psychosis 2.
• Another study found that familial breast, prostate, and colorectal cancers may have a yet unidentified genetic component associated with poorer survival, which could potentially be linked to psychosis 3.

Genetic Basis of Familial Cancer Syndromes

• Familial cancer syndromes are presumed to account for 5-10% of all cancers, and are typically characterized by early age of onset and the occurrence of cancer in multiple members of the same family 4.
• The genetic basis for many familial cancer syndromes is now understood, and genetic testing can be performed to further clarify the risk of cancer and to better target preventive strategies 4.

Psychosocial Morbidity Related to Cancer

• Cancer patients and their caregivers may experience significant psychosocial morbidity, including psychiatric and neuropsychiatric disorders, as well as other psychosocial syndromes 5.
• A family approach is necessary in cancer care, with the caregiver-patient dyad as a unit to be the focus and direction of assessment and intervention 5.

Limitations of Current Research

• While there is some evidence to suggest a link between familial cancers and psychosis, more research is needed to fully understand the relationship between these conditions 2, 3.