From the Editor

Staging psychiatric disorders: A clinico-biologic model

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Based on the above, I propose the following clinico-biologic staging model:

Stage 0: Abnormal brain development in utero due to genetic and nongenetic factors.

Stage 1a: Poor premorbid function in childhood (asociality, mediocre school performance).

Stage 1b: The prodrome, with noticeable negative symptoms, cognitive dysfunction, and gray and white matter changes.

Stage 2: First psychotic episode, with delusions and hallucinations, increasing negative symptoms, and marked cognitive decline, accompanied by frontal, parietal, and hippocampal volume losses, white matter pathology, brain edema, inflammatory markers, oxidative stress, and decreased neurotropic growth factors.

Stage 3: Second psychotic episode, with more intense psychotic and negative symptoms, cognitive dysfunction, and worsening social and vocational functioning. Biologic signs include neuroinflammation, oxidative stress and impaired neuroplasticity biomarkers, axonal degeneration and further brain tissue loss, and slower response to antipsychotics.

Stage 4: Several psychotic episodes (subchronic phase), with residual positive and negative symptoms and continued cognitive impairment especially in memory, executive function, attention and verbal learning, accompanied by glial cell death, decline in dendritic spines, retraction or neurite extension, and low response to antipsychotics, with a Global Assessment of Functioning (GAF) score of 30 to 40.

Stage 5: Refractory, unremitting psychosis (chronic phase), with poor response to antipsychotics, severe clinical, social, and functional deterioration, inability to care for oneself, severe neurodegeneration (widespread brain atrophy and dysconnectivity), and GAF score ≤30.

This staging model implies that early intervention to prevent the first or second episode may be the best approach to arrest (and perhaps reverse) psychobiologic deterioration and modify the trajectory of serious psychiatric brain disorders. More can be done to prevent a downhill course in psychosis, and emphasizing the clinical and neurobiologic features of each stage of illness may serve as a roadmap for aggressive treatment approaches early in the illness course. Until a cure is found, prevention and early intervention are the best approaches. Staging models should be incorporated in future versions of the DSM so that psychiatric practitioners can implement the optimal treatment algorithm at the earliest stage possible. Readers’ opinions are welcome!

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