CCMTV临床频道 - 荟萃名家聚焦临床

CINP 2026｜Ole Andreassen教授解析精神疾病遗传学里程碑突破、转化瓶颈与精准医疗前景

CCMTV精神频道 1368次浏览

2026-07-10

2026年6月26日-29日，第37届世界神经精神药理学大会（CINP2026）在英国格拉斯哥举行！这是时隔25年，世界神经精神药理学大会再度回归英国举办，本届大会以“携手促进脑健康（Advancing Brain Health Together）”为主题，汇聚全球领域顶尖专家共探前沿进展，是神经精神药理学领域的又一世界级盛会。

CCMTV精神频道作为大会官方唯一授权中国媒体，特别邀请到大会主旨演讲嘉宾、奥斯陆大学Ole Andreassen教授围绕精神疾病遗传学领域过去十年的里程碑式突破、从基因发现到临床转化的核心瓶颈，以及精准精神病学未来的应用前景等核心议题，分享他的深刻洞察与前瞻思考。

△专家精彩视频

Your keynote lecture at this congress focuses on "Genetics of Psychiatric Disorders - From Discoveries to Clinical Translation". In your view, what have been the most landmark breakthroughs in psychiatric genetics over the past decade, and how have these advances fundamentally transformed the field?

您本次的大会主旨演讲聚焦于“精神疾病遗传学从发现到临床转化”，您认为过去十年里，精神疾病遗传学领域最具里程碑意义的突破是什么？这些突破为整个学科的发展带来了哪些根本性的改变？

Ole Andreassen 教授

The most significant discoveries in psychiatric genetics have been the identification of specific genetic variants associated with mental illness. Although it has long been established that mental illnesses are heritable—that is, they cluster in families—the principal challenge has been to pinpoint the precise molecular variants responsible for this heritability.

Thanks to advances in genotyping technologies and the availability of large-scale samples, we have witnessed a series of discoveries regarding genetic risk factors for a range of psychiatric conditions, including schizophrenia, bipolar disorder, depression, ADHD, autism, and PTSD, as well as related traits. These findings represent major breakthroughs and have fundamentally transformed the field.

Furthermore, these discoveries have catalyzed new research initiatives aimed at elucidating the underlying biological and molecular mechanisms involved in the development of mental illness. Such mechanistic insights hold promise for the identification of novel drug targets—if the molecular pathways are understood, they can serve as sites for therapeutic intervention, potentially reducing disease burden. In parallel, there are important implications for clinical translation, particularly in the realm of precision medicine. Specifically, genetic risk profiles may enable clinicians to determine which patients are most likely to respond to a given medication, to initiate earlier interventions, or to design personalized prevention strategies. These two directions—biological discovery and clinical application—constitute the primary transformations currently reshaping the field, driven by the large-scale identification of genetic factors in mental disorders.

精神病遗传学领域最重要的发现，在于鉴定出了与精神疾病相关的特定遗传变异。尽管人们早已认识到精神疾病具有遗传性，即它们往往在家族中聚集出现，但核心挑战始终在于找到导致这种遗传性的确切分子变异。

得益于基因分型技术的进步和大规模样本的积累，我们相继鉴定出多种精神疾病的遗传风险因素，涵盖精神分裂症、双相情感障碍、抑郁症、注意缺陷多动障碍、自闭症和创伤后应激障碍等，以及相关的性状特征。这些发现具有里程碑意义，并从根本上改变了该领域的研究格局。

此外，这些发现推动了一系列旨在阐明精神疾病发病过程中所涉及的潜在生物学和分子机制的新研究计划。明确这些分子机制，能够助力发现全新的药物作用靶点，为研发新型治疗药物、降低精神疾病的疾病负担提供核心依据。与此同时，这些发现在临床转化方面也具有重要价值，尤其是在精准医学领域。具体而言，基于个体的遗传风险特征，临床医生能够确定哪些患者最有可能对某种药物产生应答，从而更早地实施干预措施，或制定个性化的预防策略。生物学机制的揭示与临床应用的推进，正是当前该领域在精神疾病遗传因素大规模发现驱动下所经历的两大核心变革。

From your perspective, what are the main bottlenecks currently hindering the translation of psychiatric genetics research into clinical practice? How can we systematically address these challenges?

在您看来，目前精神疾病遗传学研究向临床应用转化的主要瓶颈是什么？我们应该如何系统性地去克服这些挑战？

Ole Andreassen 教授

What we are looking forward to is the discovery of new drug targets that can lead to the development of novel therapeutics. This represents a long-term challenge, as it requires substantial resources and collaborative efforts across research institutes. One key aspect is elucidating the biological mechanisms amenable to drug intervention, which is a long-term goal demanding expertise and sustained investment, and may take considerable time to materialize.

However, another bottleneck lies in engaging manufacturers and the pharmaceutical industry to invest in and advance new drug development. We have observed several instances where drug development grounded in genetic findings has proven more successful than other approaches. Another bottleneck concerns the translation of these discoveries into clinical practice. This translational challenge is particularly pronounced in precision medicine—or what we also call precision psychiatry. Here, the key difficulty is identifying appropriate use cases. To fully leverage genetic findings in psychiatry, geneticists and clinicians must collaborate closely to determine the most valuable translational scenarios.

Specifically, we must determine where genetic factors can deliver tangible clinical benefits. One approach that has been advanced is the polygenic risk score (PRS), which aggregates the effects of numerous genetic variants to predict disease liability. However, the current paradigm has yet to yield PRS models with sufficient clinical utility in psychiatry. There are several reasons for this, the foremost being that their predictive accuracy remains insufficient for clinical application. In addition, we may not yet have identified the right use cases. For example, we now have reasonably good PRS for major psychiatric disorders, like schizophrenia, derived from large-scale genetic studies comparing schizophrenia patients with healthy controls. However, if a patient presents to a hospital with clear schizophrenia symptoms and is unequivocally diagnosed, obtaining a PRS for schizophrenia adds little clinical value, because the diagnosis is already evident from the symptoms.

Therefore, finding the right clinical applications for genetic discoveries in psychiatry is an urgent task that requires close collaboration between clinicians and molecular geneticists.

我们期待的是发现新的药物靶点，从而推动新型疗法的研发。这是一项长期挑战，需要大量资源以及跨研究机构的协作努力。其中关键的一环是阐明可被药物干预的生物学机制，这一长期目标需要专业知识和持续投入，可能需要相当长的时间才能实现。

然而，另一个瓶颈在于吸引制造商和制药行业投资并推进新药研发。我们已观察到，基于基因研究成果的药物开发在某些情况下比其他方法更为成功。另一个瓶颈则在于将这些发现转化为临床实践。这种转化挑战在精准医学——也就是我们所说的精准精神病学领域尤为突出。在此，关键难题在于识别合适的应用案例。要充分利用基因在精神医学中的价值，遗传学家与临床医生必须密切合作，共同确定最具价值的转化应用场景。

具体而言，我们必须明确遗传因素在哪些方面能够带来切实的临床益处。目前提出的一种方法是多基因风险评，它通过汇总多种基因变异的影响来预测疾病易感性。然而，当前的范式尚未在精神病学领域产生具有足够临床实用价值的PRS模型。这背后存在多个原因，其中最主要的是其预测准确性仍不足以用于临床应用。此外，我们可能尚未找到合适的使用场景。例如，目前已有基于大规模基因研究的PRS，用于评估精神分裂症等主要精神疾病的风险，这些研究将精神分裂症患者与健康对照人群进行比较。但若一名患者因明显的精神分裂症症状被送入医院，并已明确诊断，则再获取精神分裂症的PRS几乎不会增加临床价值，因为该诊断已由症状本身所体现。因此，在精神病学中寻找遗传发现的合适临床应用，是一项紧迫的任务，需要临床医生与分子遗传学家密切合作。

For clinicians and patients, which areas are most likely to see the first tangible benefits from advances in psychiatric genetics research—such as diagnosis, treatment, prognosis prediction, or disease prevention? Which of these directions do you believe holds the most promising clinical future?

对于临床医生和患者而言，精神疾病遗传学研究的进展，最有可能在哪些方面率先带来可感知的获益？比如诊断、治疗、预后预测或疾病预防，您认为哪个方向的应用前景最值得期待？

Ole Andreassen 教授

I believe the most important application will be to leverage genetic discoveries to develop new medications with fewer side effects and improved response rates. However, as we have discussed, ultimately this depends on whether pharmaceutical companies are willing to invest in such endeavors.Another promising avenue is the polygenic risk score (PRS), which aggregates the effects of numerous risk variants into a single metric applicable to genotyped individuals. Nevertheless, this approach is not yet clinically applicable.

As we noted, genetic testing offers little diagnostic value for a patient already hospitalized with clear symptoms of schizophrenia; there is no need to conduct a genetic test to confirm a diagnosis that is already clinically evident. This reflects the current design of genome-wide association studies, which aim to identify variants that are more frequent in patients than in healthy controls.

To advance the field, we need to identify appropriate clinical use cases. For instance, genetic studies comparing treatment responders and non-responders are now being conducted through large international initiatives. These studies aim to uncover genetic factors associated with antipsychotic response. This represents a highly beneficial clinical application, as it would allow genetic testing prior to treatment initiation to guide medication selection. In this context, perfect prediction is not required; rather, the test could serve as clinical decision support. This approach is currently under development.

Another promising avenue is early diagnosis. For example, when a patient presents with early, non-specific symptoms, it may be unclear whether the condition is one mental illness or another, making it difficult to initiate treatment. In such cases, a polygenic risk score could be used to estimate the likelihood of one disorder versus another. This requires comparative genetic studies between these conditions, which are underway.

Finally, I believe a particularly valuable application of polygenic or precision medicine tools lies in differentiating a depressive episode occurring in the context of unipolar depression versus bipolar disorder. A depressive episode can manifest in both conditions, and it is often difficult to determine, especially during the first mood episode without prior manic or hypomanic episodes. In this setting, genetic information could help assess whether a patient with depression is more likely to have bipolar disorder, thereby guiding appropriate treatment—such as mood stabilizers for bipolar disorder or antidepressants for unipolar depression.

In summary, there are specific clinical scenarios where these novel tools could be applied. However, to realize this potential, we must develop more refined genetic studies that identify the factors associated withprecise clinical scenarios.

我认为，基因发现最重要的应用将是推动新型药物的研发，这些药物应具备更少的副作用和更高的应答率。然而，正如我们之前所讨论的，这最终取决于制药公司是否愿意为此类探索投入资源。另一个有前景的方向是多基因风险评，该方法将众多风险变异位点的效应整合为单一指标，可应用于已进行基因分型的个体。不过，这一方法目前尚不具备临床适用性。

正如我们所指出的，对于已因精神分裂症明确症状而住院的患者，基因检测在诊断方面的价值极为有限；对于已具显著临床表现的病例，无需通过基因检测来印证诊断。这反映了当前全基因组关联研究的设计思路，即旨在识别在患者群体中出现频率高于健康对照群体的变异位点。

为了推动该领域的发展，我们亟需明确适用的临床场景。例如，目前已有大型国际合作项目正在开展针对治疗应答者与无应答者的基因研究，旨在揭示与抗精神病药物反应相关的遗传因素。这代表了一种极具临床实用价值的应用方向，因为可在治疗启动前进行基因检测，以指导药物选择。在此情境下，无需达到完美的预测能力，而是将该检测作为临床决策支持工具。该方案目前正处于研发进程中。

另一个有前景的方向是早期鉴别诊断。例如，当患者呈现早期非特异性症状时，可能难以明确其病种属于某一精神疾患还是另一类，从而延误治疗启动。在此类情况下，可采用多基因风险评分来评估罹患某种障碍相较另一种障碍的可能性。这需要在不同疾病之间开展比较性遗传研究，而此类研究正在进行中。

最后，我认为多基因或精准医学工具的一个特别有价值的应用场景，在于区分单相抑郁背景下所发生的抑郁发作与双相障碍中的抑郁发作。抑郁发作可同时出现于这两种疾病中，且尤其在首次心境发作且缺乏既往躁狂或轻躁狂发作史的情况下，鉴别往往十分困难。在此情境下，遗传信息有助于评估抑郁患者更可能罹患双相障碍，从而指导合理治疗——例如针对双相障碍使用心境稳定剂，或针对单相抑郁使用抗抑郁药。

总而言之，存在特定的临床情境可应用这些新兴工具。然而，要真正实现这一潜力，我们必须开展更加精细的遗传学研究，以揭示与具体临床情境相关的遗传因素。

专家介绍

Expert presentation

Ole Andreassen

University of Oslo

Professor in psychiatry at University of Oslo, and Director of Centre for Precision Psychiatry. Andreassen did his PhD in psychopharmacology at University of Bergen and post doc training in molecular neuroscience at Massachusetts General Hospital, Harvard Medical School. He did his psychiatry residency at Oslo University Hospital and is now attending psychiatrist at the Bipolar Disorder Clinic.

审核专家：Ole Andreassen教授

整理：CCMTV精神频道

【免责声明】本文仅供医学学术交流与专业知识分享，不构成任何临床诊疗依据，亦不作为药品、医疗器械的商业推广或诊疗指导。文中内容与本文所提及的相关企业无任何直接或间接利益关联；所有观点均基于专家个人临床实践及公开学术研究，立场客观中立，绝无商业利益倾向。CCMTV平台仅作为学术传播交流载体，不对内容的临床应用承担任何医疗及法律责任。读者在作出任何临床决策前，请严格遵循国家诊疗规范及法律法规。

发送