Alto Neuroscience Inc., Los Altos, CA, 94022, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94304, USA.
Neuropsychopharmacology. 2024 Nov;50(1):258-268. doi: 10.1038/s41386-024-01970-8. Epub 2024 Aug 21.
Neuroimaging, across positron emission tomography (PET), electroencephalography (EEG), and magnetic resonance imaging (MRI), has been a mainstay of clinical neuroscience research for decades, yet has penetrated little into psychiatric drug development beyond often underpowered phase 1 studies, or into clinical care. Simultaneously, there is a pressing need to improve the probability of success in drug development, increase mechanistic diversity, and enhance clinical efficacy. These goals can be achieved by leveraging neuroimaging in a precision psychiatry framework, wherein effects of drugs on the brain are measured early in clinical development to understand dosing and indication, and then in later-stage trials to identify likely drug responders and enrich clinical trials, ultimately improving clinical outcomes. Here we examine the key variables important for success in using neuroimaging for precision psychiatry from the lens of biotechnology and pharmaceutical companies developing and deploying new drugs in psychiatry. We argue that there are clear paths for incorporating different neuroimaging modalities to de-risk subsequent development phases in the near to intermediate term, culminating in use of select neuroimaging modalities in clinical care for prescription of new precision drugs. Better outcomes through neuroimaging biomarkers, however, require a wholesale commitment to a precision psychiatry approach and will necessitate a cultural shift to align biopharma and clinical care in psychiatry to a precision orientation already routine in other areas of medicine.
神经影像学,包括正电子发射断层扫描(PET)、脑电图(EEG)和磁共振成像(MRI),几十年来一直是临床神经科学研究的主要手段,但除了通常功率不足的 1 期研究,或者进入临床护理,它在精神药物开发方面的应用很少。与此同时,迫切需要提高药物开发的成功率,增加机制多样性,并提高临床疗效。这些目标可以通过在精准精神病学框架中利用神经影像学来实现,即在临床开发的早期测量药物对大脑的影响,以了解剂量和适应症,然后在后期试验中识别可能的药物反应者,并丰富临床试验,最终改善临床结果。在这里,我们从开发和部署精神科新药的生物技术和制药公司的角度,检查了在精准精神病学中使用神经影像学取得成功的关键变量。我们认为,有明确的途径可以整合不同的神经影像学模式,以降低随后的开发阶段的风险,最终在临床护理中使用特定的神经影像学模式,为新的精准药物开处方。然而,通过神经影像学生物标志物实现更好的结果需要全面承诺采用精准精神病学方法,并且需要将生物制药和临床护理在精神病学中的文化转变为已经在医学其他领域常规应用的精准方向。