Gee Abigail, Dazzan Paola, Grace Anthony A, Modinos Gemma
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Transl Psychiatry. 2025 Jan 24;15(1):21. doi: 10.1038/s41398-024-03221-2.
Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set of cortical and subcortical brain regions critically involved in this process. Understanding how neural circuitry and molecular mechanisms within this corticolimbic system may contribute to the development of not only positive symptoms but also negative and cognitive deficits in SSD has been a recent focus of intense research, as the latter are not adequately treated by current antipsychotic medications and are more strongly associated with poorer functioning and long-term outcomes. This review synthesises recent developments examining corticolimbic dysfunction in the pathophysiology of SSD, with a focus on neuroimaging advances and related novel methodologies that enable the integration of data across different scales. We then integrate how these findings may inform the identification of novel therapeutic and preventive targets for SSD symptomatology. A range of pharmacological interventions have shown initial promise in correcting corticolimbic dysfunction and improving negative, cognitive and treatment-resistant symptoms. We discuss current challenges and opportunities for improving the still limited translation of these research findings into clinical practice. We argue how our knowledge of the role of corticolimbic dysfunction can be improved by combining multiple research modalities to examine hypotheses across different spatial and temporal scales, combining neuroimaging with experimental interventions and utilising large-scale consortia to advance biomarker identification. Translation of these findings into clinical practice will be aided by consideration of optimal intervention timings, biomarker-led patient stratification, and the development of more selective medications.
精神分裂症谱系障碍（SSD）涉及感知、情感和认知整合方面的紊乱。皮质边缘系统是一组相互作用的皮质和皮质下脑区，在这一过程中起着关键作用。了解该皮质边缘系统内的神经回路和分子机制如何不仅导致SSD的阳性症状，还导致阴性症状和认知缺陷，已成为近期深入研究的焦点，因为目前的抗精神病药物对后者治疗效果不佳，且后者与功能较差和长期预后的关联更为密切。本综述综合了近期关于SSD病理生理学中皮质边缘功能障碍的研究进展，重点关注神经影像学进展以及相关的新方法，这些方法能够整合不同尺度的数据。然后，我们整合这些发现如何为识别SSD症状的新型治疗和预防靶点提供信息。一系列药物干预措施已在纠正皮质边缘功能障碍以及改善阴性、认知和难治性症状方面显示出初步前景。我们讨论了目前在将这些研究结果转化为临床实践方面仍然有限的情况下所面临的挑战和机遇。我们认为，通过结合多种研究模式来检验不同空间和时间尺度上的假设、将神经影像学与实验干预相结合以及利用大规模联盟来推进生物标志物识别，可以提高我们对皮质边缘功能障碍作用的认识。考虑最佳干预时机、生物标志物引导的患者分层以及开发更具选择性的药物，将有助于将这些发现转化为临床实践。
