Intervention in the progression of schizophrenia is an effort not just to deter psychosis but also to protect the brain from physiologic deterioration. Neurodegeneration is believed to result from neurochemical dysregulation during the onset of schizophrenia. Deterioration accrued over recurring psychotic episodes causes cumulative loss of cell processes, loss of gray matter volume, and apoptosis. Neurodegeneration ultimately results in persistent symptomology and functional impairment. Functional decline occurs early in the course of schizophrenia, and the symptoms that emerge during the prodromal stage may derail the normal adolescent neurodevelopment. Both first-episode psychosis and the prodrome may be opportunities to forestall neurodegeneration. Unfortunately, people with schizophrenia often experience a long duration of untreated psychosis. Treatment of first-episode psychosis with antipsychotic agents shows robust response. However, early-stage patients have very high rates of medication noncompliance. Treatment in the prodrome may offer the best chance to delay the onset of illness, mitigate its severity after onset, or even prevent onset of symptoms entirely. Nonpharmacologic treatments during the prodrome, such as education, treatment for substance use, and cognitive-behavioral therapy, are low-risk interventions that are potentially beneficial. Pharmacologic interventions during the prodrome are also effective in delaying onset of illness, but carry the risk of adversely affecting patients who are false positives for prodromal schizophrenia.

In this Expert Roundtable Supplement, Jeffrey A. Lieberman, MD, provides an overview of the neurobiological basis of neurodegeneration and the concept of neuroprotection. Next, Peter F. Buckley, MD, reviews the importance of first-episode psychosis, including duration of untreated illness and medication adherence. Finally, Diana O. Perkins, MD, MPH, reviews treatment strategies for prodromal schizophrenia.