Miller Andrew H, Berk Michael, Bloch Gilles, Briquet-Laugier Veronique, Brouillon Carinne, Cuthbert Bruce N, Dantzer Robert, Davis Michael C, De Picker Livia J, Drevets Wayne C, Eyre Harris A, Hack Laura M, Harrison Neil A, Krystal Andrew D, Lombardo Giulia, Mondelli Valeria, Pariante Carmine M, Pulvirenti Luigi, Salvadore Giacomo, Sforzini Luca, Swieboda Pawel, Trivedi Madhukar H, Leboyer Marion
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine and Barwon Health, Deakin University, Geelong, VIC 3220, Australia.
Brain Behav Immun. 2025 Mar;125:319-329. doi: 10.1016/j.bbi.2025.01.002. Epub 2025 Jan 17.
Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood. Precision psychiatry is a strategy that holds great promise for novel therapies targeting specific pathophysiologic mechanisms in selected patients, ultimately contributing to more effective, personalized treatments. Immunopsychiatry, which focuses on the immune system's role in psychiatric disorders, exemplifies the challenges and potential solutions for precision psychiatry. Despite understanding how inflammation contributes to psychiatric illness, results of clinical trials with anti-inflammatory drugs have been inconsistent and underwhelming. Shortcomings of these trials include a lack of focus on subgroups of patients with increased inflammation, the use of non-specific outcome variables (e.g., not specific to inflammation's impact on the brain and behavior), and failure to establish target engagement of the inflammatory response. To advance anti-inflammatory treatments, clinical trials should: 1) enrich for patients using predictive biomarkers; 2) use clinical outcome assessments that align with inflammation's effects on the brain; 3) consider novel diagnostic constructs linked to inflammation; and 4) verify target engagement. Moreover, greater attention should be paid to efforts to repurpose available anti-inflammatory drugs while awaiting development of novel treatments targeting more specific immune pathways. Taken together, a collaborative approach involving academia, industry, funding agencies, patients, payors, and policymakers is required to advance Immunopsychiatry and ultimately provide a roadmap for successful implementation of precision psychiatry.
尽管神经科学取得了巨大进展，但对患者护理的影响仍然有限。当前的精神科治疗在很大程度上缺乏特异性，药物开发受到过时、涵盖范围过广的诊断类别和“一刀切”方法的阻碍。此外，精神疾病的潜在机制及其传统药物治疗方法仍未得到充分理解。精准精神病学是一种有望针对特定患者的特定病理生理机制开发新疗法的策略，最终有助于实现更有效、个性化的治疗。免疫精神病学专注于免疫系统在精神疾病中的作用，它体现了精准精神病学面临的挑战和潜在解决方案。尽管人们了解炎症如何导致精神疾病，但抗炎药物的临床试验结果却不一致且不尽人意。这些试验的缺点包括：缺乏对炎症增加的患者亚组的关注、使用非特异性的结果变量（例如，并非特定于炎症对大脑和行为的影响）以及未能确定炎症反应的靶点参与情况。为了推进抗炎治疗，临床试验应：1）使用预测性生物标志物富集患者；2）使用与炎症对大脑的影响相一致的临床结局评估；3）考虑与炎症相关的新型诊断结构；4）验证靶点参与情况。此外，在等待针对更特定免疫途径的新疗法开发的同时，应更加关注现有抗炎药物的重新利用。总之，需要学术界、产业界、资助机构、患者、支付方和政策制定者采取合作方法，以推进免疫精神病学，并最终为成功实施精准精神病学提供路线图。
