Abstract
<title>Abstract</title> <p>Background The nervous system and the immune system are intricately connected. Abnormal neuroimmune responses can be activated due to stress, trauma and other environmental influences, which may cause disorders in emotions, social behavior and cognitive abilities, and ultimately lead to the occurrence of psychiatric disorders. Differences in the regional vulnerability to cortical abnormalities exist in different psychiatric disorders. However, the immunological mechanisms underlying this regional vulnerability, as well as the commonalities and specificities across different disorders, remain unclear. Methods In this study, we integrated the cortical abnormality maps of six psychiatric disorders from the ENIGMA consortium with the intrinsic expression of immune genes derived from the Allen Brain Atlas. Using partial least square regression and gene set enrichment analysis, we obtained the common and specific covarying patterns between abnormal cortical thickness and immune gene expression across six psychiatric disorders. Results Our results on covarying patterns across psychiatric disorders revealed two immune-related vulnerability clusters: the negative vulnerability cluster was mainly enriched in microglia activation and cytokine secretion; the positive vulnerability cluster was enriched in lymph node development and the regulation of T cell differentiation. Moreover, our findings suggested that disorder-specific covarying pattern analysis showed distinct immune-related pathways for ADHD, ASD, and non-developmental disorders. When gene enrichment was validated against the whole-brain gene transcriptome, none of these disorders showed a clear bias towards innate or adaptive immunity. Conclusion These findings offer new insights into the mechanisms of vulnerability to psychiatric disorders and provide a neuroimmune perspective on specific preventive approaches for different psychiatric disorders.</p>