Psychosis as a Neurodevelopmental Spectrum: Beyond the Degeneration Paradigm
For decades, prevailing models of psychosis-including schizophrenia and various neurodegenerative disorders have largely interpreted hallucinations and delusions through the lens of neurodegeneration and neurotransmitter imbalance. In this view, psychotic symptoms emerge as the consequence of progressive and largely irreversible neural decline. Yet, an alternative picture has begun to emerge from accumulating evidence. Rather than reflecting only loss, psychosis in a subset of cases may represent a fundamentally different developmental trajectory one that resembles a re-emergence of early, highly plastic brain states. We refer to this hypothesis as “pathological neoteny,” in which the brain appears, in certain respects, to revert toward immature modes of cognition characterized by heightened plasticity and reduced constraints on internal representations. Intriguingly, many phenomenological features of psychosis-such as vivid internal imagery, weakened boundaries between perception and imagination and intensified associative thinking echo aspects of normative childhood cognition. However, while these similarities are striking, the underlying mechanisms remain poorly understood and the boundary between developmental plasticity and clinical pathology remains unclear. In this Perspective, we bring together emerging neuroimaging and molecular evidence that points toward atypical developmental timing, including delayed maturation and sustained plasticity in specific psychotic subgroups. We situate these findings against established frameworks in developmental neuroscience, particularly synaptic pruning, critical period closure and the adaptive advantages of childhood neural flexibility. Importantly, we emphasize that psychosis is heterogeneous: not all cases can be explained within a single framework. We therefore highlight the need to carefully distinguish normative childhood imagination from pathological states, while also acknowledging the conceptual, methodological and ethical challenges inherent in this distinction. Looking forward, we propose a research agenda centered on longitudinal, multi-modal developmental comparisons, biologically grounded subgroup stratification and mechanistic mapping of how plasticity itself might become dysregulated. Such work also raises translational questions both promising and cautionary-regarding whether and how brain plasticity could be therapeutically modulated. Taken together, this re-evaluation challenges the long-standing assumption that psychosis is solely a story of decline, instead suggesting a more nuanced narrative in which altered developmental timing and plasticity may play a central role in shaping mental experience and its disorders.