The effect of polygenic risk scores for major depressive disorder, bipolar disorder and schizophrenia on morphological brain measures: A systematic review of the evidence

Background: Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SCZ) share clinical features and genetic bases. Magnetic Resonance Imaging (MRI) studies assessing the effect of polygenic risk score (PRS) for psychiatric disorders on brain structure show heterogeneous results. Therefore, we provided an overview of the existing evidence on the association between PRS for MDD, BD and SCZ and MRI abnormalities in clinical and healthy populations. Methods: A search on PubMed, Web of Science and Scopus was performed to identify the studies exploring the effect of PRS for MDD, BD and SCZ on MRI measures. A total of 25 studies were included (N = 13 on healthy individuals and N = 12 on clinical populations). Results: Both in affected and unaffected individuals, PRS for BD and SCZ showed either positive or negative correlations with cortical thickness (CT), mostly involving fronto-temporal areas, whereas PRS for MDD was associated with cortical alterations in prefrontal regions in healthy subjects. Limitations: The heterogeneity in the methods limits the conclusions of this review. Conclusions: Overall the evidence on the effect of PRS for MDD, BD and SCZ on brain is considerably heterogeneous and far to be conclusive. However, from the results emerged that PRS for MDD, BD and SCZ were associated with widespread cortical abnormalities in all the populations explored, suggesting that genetic risk for MDD, BD and SCZ might affect neurodevelopmental processes, resulting in cortical alterations that transcend diagnostic boundaries and seem to be independent from the clinical status.