Psychotic Disorders and exosomes: An overview of current evidence and future directions

•Precise diagnosis of psychosis facilitates early intervention, and supports recovery.•The lack of specific biomarkers limits early diagnosis and intervention.•Circulating and brain-derived exosomes are potential blood biomarkers of psychosis.•Future investigations need to consider the multifactorial context of psychosis. Due to its reliance on heterogeneous symptomatology, the accurate diagnosis of psychotic disorders remains a challenging task in clinical practice. Precise and early diagnosis of psychotic disorders facilitates early intervention, which has been shown to have substantial benefits for long-term outcomes. Still, the lack of specific biomarkers is an important limitation in early diagnosis and intervention. Exosomes, which act as messengers between cells, including brain cells, contain a vast array of molecules that hold promise for unveiling disorder-specific abnormalities. In this review, we discuss recent evidence highlighting the potential of circulating exosomes and brain-derived exosomes as valuable tools for the identification of accessible, non-invasive, and blood-based biomarkers of psychotic symptomatology and risk. We discuss current limitations in biomarker discovery studies focusing on exosomes. To enhance diagnosis specificity and treatment response, we also provide guidance for future investigations that need to target biomarkers of risk and relapse, as well as consider duration of untreated psychosis, biological sex, and other factors in the multifactorial biosignature of psychosis.