One unified hypothesis of neuropsychiatric disorders: Transdiagnostic common staging models

Much like physicists perpetually seek a grand unified theory capable of making predictions for particles within the same theoretical framework, the idea that diverse clinical presentations of psychiatric disorders might be explained by common biological mechanisms is of interest to those in the field of biopsychiatry. Despite the attempts made by the Research Domain Criteria (RDoC) to develop a more physiologically oriented diagnostic concept, departing from phenotype-driven diagnostic systems such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), the complexity of the RDoC matrix has made it challenging for those accustomed to conventional approaches. In this paper, I endeavor to integrate the diathesis-stress model, the allostatic load model, and the kindling model into what I term “transdiagnostic common staging models.” From this model, shared aspects among different traditional diagnostic categories become apparent, encompassing concepts such as excitatory-inhibitory imbalance, inflammation, inflexibility, and sensitization. While it is possible that different traditional categories may lean towards different neurocircuits or neurotransmitters, I also propose the potential for cross-system interactions. This approach may offer a promising avenue for understanding the complex interplay of biological mechanisms underlying psychiatric disorders, shedding light on their commonalities and differences.