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.

了解人类疾病的科学进步可以通过其治疗的有效性来衡量。抗精神病药已被证明可减轻急性精神病症状并防止其在精神分裂症中复发，但历史上多数患者的治疗效果欠佳。然而，对首发精神分裂症患者的研究中的一系列发现改变了精神病学领域对病理生理，病程和可能改变疾病治疗效果的思考。这些包括未经治疗的精神病症状的持续时间与预后之间的关系；与慢性病患者相比，首发患者对抗精神病药的反应更好，并且在病程中脑灰质量减少。对早期发现和干预模式的有效性的研究在限制发病率和改变病程方面提供了令人鼓舞但不确定的结果。尽管如此，首发性精神病研究已经建立了证据基础，考虑将基于团队的，协调的专业方法作为治疗早期精神病的护理标准，这导致了它们的全球扩散。相比之下，尽管临床高风险研究已经开发出了一种基于证据的护理模型来减轻症状减轻的负担，但尚无治疗可降低风险或预防过渡为精神病的证据。此外，当前针对临床高风险的诊断标准缺乏对临床应用的足够特异性。限制我们实现早期发现和干预模型的潜力的能力是缺乏针对综合征前精神分裂症的敏感且特定的诊断标准，经过验证的生物标志物和可靠的治疗策略。未来的研究需要跨多个地点对大量患者样本进行严格的方法学研究，理想情况下，应以有可靠证据的科学可靠的病理生理学理论为指导。尽管有这些警告，但我们可以合理地预期未来的研究将以过去四个十年的研究为基础，以增进我们的知识并使这种改变游戏规则的护理模式成为现实。和行之有效的治疗策略。未来的研究需要跨多个地点对大量患者样本进行严格的方法学研究，理想情况下，应以有可靠证据的科学可靠的病理生理学理论为指导。尽管有这些警告，但我们可以合理地预期未来的研究将以过去四个十年的研究为基础，以增进我们的知识并使这种改变游戏规则的护理模式成为现实。和行之有效的治疗策略。未来的研究需要跨多个地点对大量患者样本进行严格的方法学研究，理想情况下，应以有可靠证据的科学可靠的病理生理学理论为指导。尽管有这些警告，但我们可以合理地预期未来的研究将以过去四个十年的研究为基础，以增进我们的知识并使这种改变游戏规则的护理模式成为现实。