Psychiatry continues to struggle with the heterogeneity of mental disorders. Classifications such as DSM and ICD catalogue symptom clusters but fail to reveal underlying mechanisms. Recent integrative approaches, including the biopsychosocial model and RDoC, have advanced the field, yet psychiatry still lacks a unifying explanatory principle. We propose the Predictive Dysfunction Hypothesis as a conceptual framework—a paradigm rather than a proven theory. It suggests that psychiatric disorders can be understood as variations of a fundamental disruption in the brain’s predictive machinery. From an evolutionary standpoint, the brain’s primary role is not to represent the world accurately, but to anticipate potential dangers in order to ensure survival. When this survival-oriented predictive system becomes miscalibrated, psychopathology may arise. This hypothesis integrates predictive processing and active inference models with clinical psychiatry. Psychosis may be seen as overweighted priors, PTSD as rigid threat models, panic disorder as catastrophic interoceptive predictions, depression as entrenched negative priors, OCD as unresolved prediction errors, autism as overweighted sensory errors, and anxiety as exaggerated threat priors. Like oncology’s unification around disordered cell division, psychiatry may benefit from a unifying lens. The Predictive Dysfunction Hypothesis is offered not as a replacement for existing frameworks but as a conceptual paradigm that invites empirical testing and inspires new ways of thinking about diagnosis and treatment.
Esther Malkah van Fenema (Wed,) studied this question.