Functional immunogenomics and deep clinical phenotyping to resolve the challenges of heterogeneity in mental...

Historically, the field of psychiatry has relied on descriptive categories, as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD). However, with increasing knowledge of molecular processes that contribute to mental disorders, the descriptive approach has been criticised. The current descriptive diagnostic categories lack sensitivity and specificity; as such, diagnostic heterogeneity remains a challenge for clinics and research. The search for more homogeneous patient groups is fuelled by both the molecular background, looking into molecular processes, pleiotropy, transdiagnostic, and diagnosis-specific markers, as well as from the phenotypic perspective. Immune-related molecular endophenotypes, as well as deep phenotyping, have been suggested as an approach to reduce the challenge of heterogeneity. This literature review focuses on functional immunogenomics, deep clinical phenotyping, and other approaches currently being discussed to resolve the burden of heterogeneity for mental disorders and provides a multidisciplinary perspective and roadmap towards reducing the impact of heterogeneity for research. With the current literature at hand, we provide evidence for the thesis that functional immunogenomics combined with deep clinical phenotyping offers a viable strategy to reduce the influence of heterogeneity.