Immunogenetic Variants in Major Mental and Neurodevelopmental Disorders

Major mental disorders (MMDs) are frequent, chronic heterogeneous disorders with complex etiopathology. This review specifically focuses on the immunogenetic variants associated with bipolar disorder, recurrent depression, schizophrenia, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The cumulative evidence suggests that abnormal immune processes may play a pivotal role in inducing chronic low-grade inflammation in subgroups of patients with these MMDs, leading to poor prognosis, treatment resistance, and progressive functional decline. Interaction between immunogenetic background and environmental risk factors (infections, pollution, stress, etc.) contribute to this low-grade inflammation, highlighting the need to better understand the role of immune genes and their related molecular mechanisms to better stratify patients and better treat homogeneous subgroups of patients with inflammation. Both innate and adaptive immunity genes may contribute to this background. In particular, the Psychiatric Genomics Consortium (PGC) identified major histocompatibility complex region associations in both schizophrenia and bipolar disorder. In this review, we summarize the state of knowledge on immunogenetic variants associated with MMDs, focusing on both innate and adaptive immunity to discuss gaps and steps for the future of translational research in immunopsychiatry. Addressing these gaps may improve patient stratification based on immunogenetic information and support the development of personalized therapeutic strategies.