Early Detection and Preventive Intervention in Schizophrenia: From Fantasy to Reality.

Scientific progress in understanding human disease can be measured by the effectiveness of its treatment. Antipsychotic drugs have been proven to alleviate acute psychotic symptoms and prevent their recurrence in schizophrenia, but the outcomes of most patients historically have been suboptimal. However, a series of findings in studies of first-episode schizophrenia patients transformed the psychiatric field's thinking about the pathophysiology, course, and potential for disease-modifying effects of treatment. These include the relationship between the duration of untreated psychotic symptoms and outcome; the superior responses of first-episode patients to antipsychotics compared with patients with chronic illness, and the reduction in brain gray matter volume over the course of the illness. Studies of the effectiveness of early detection and intervention models of care have provided encouraging but inconclusive results in limiting the morbidity and modifying the course of illness. Nevertheless, first-episode psychosis studies have established an evidentiary basis for considering a team-based, coordinated specialty approach as the standard of care for treating early psychosis, which has led to their global proliferation. In contrast, while clinical high-risk research has developed an evidence-based care model for decreasing the burden of attenuated symptoms, no treatment has been shown to reduce risk or prevent the transition to syndromal psychosis. Moreover, the current diagnostic criteria for clinical high risk lack adequate specificity for clinical application. What limits our ability to realize the potential of early detection and intervention models of care are the lack of sensitive and specific diagnostic criteria for pre-syndromal schizophrenia, validated biomarkers, and proven therapeutic strategies. Future research requires methodologically rigorous studies in large patient samples, across multiple sites, that ideally are guided by scientifically credible pathophysiological theories for which there is compelling evidence. These caveats notwithstanding, we can reasonably expect future studies to build on the research of the past four decades to advance our knowledge and enable this game-changing model of care to become a reality.