Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review

Abbie Gee; Paola Dazzan; Anthony A. Grace; Gemma Modinos

doi:10.1038/s41398-024-03221-2

Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review

Abbie Gee, Paola Dazzan, Anthony A. Grace, Gemma Modinos

University of Pittsburgh

Research output: Contribution to journal › Review article › peer-review

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Abstract

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.

Original language	English
Article number	21
Journal	Translational psychiatry
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41398-024-03221-2
Publication status	Published - 24 Jan 2025

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Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review
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Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review
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abstract = "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.",

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Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review

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