Abstract
Depression is a highly prevalent psychological disorder characterized by persistent dysphoria, psychomotor retardation, insomnia, anhedonia, suicidal ideation, and a remarkable decrease in overall well-being. Despite the prevalence of accessible antidepressant therapies, many individuals do not achieve substantial improvement. Understanding the multifactorial pathophysiology and the heterogeneous nature of the disorder could lead the way toward better outcomes. Recent findings have elucidated the substantial impact of compromised blood-brain barrier (BBB) integrity on the manifestation of depression. BBB functions as an indispensable defense mechanism, tightly overseeing the transport of molecules from the periphery to preserve the integrity of the brain parenchyma. The dysfunction of the BBB has been implicated in a multitude of neurological disorders, and its disruption and consequent brain alterations could potentially serve as important factors in the pathogenesis and progression of depression. In this review, we extensively examine the pathophysiological relevance of the BBB and delve into the specific modifications of its components that underlie the complexities of depression. A particular focus has been placed on examining the effects of peripheral inflammation on the BBB in depression and elucidating the intricate interactions between the gut, BBB, and brain. Furthermore, this review encompasses significant updates on the assessment of BBB integrity and permeability, providing a comprehensive overview of the topic. Finally, we outline the therapeutic relevance and strategies based on BBB in depression, including COVID-19-associated BBB disruption and neuropsychiatric implications. Understanding the comprehensive pathogenic cascade of depression is crucial for shaping the trajectory of future research endeavors.
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References
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Acknowledgements
The authors would like to thank Dr. Lalitha Biswas, Associate Professor, Amrita School of Nanosciences and Molecular Medicine for the recommendations.
Funding
The work was supported by Amrita Vishwa Vidyapeetham to AKV and partly by SERB-POWER Fellowship to SC [SPF/2021/000045].
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SMV and SP were involved in conceptualization, data curation, formal analysis, and writing—original draft preparation and review and editing. AN, AJ, SG, and RS were involved in data curation, formal analysis, and writing—original draft preparation. BM and LB were involved in supervision and writing—review and editing. AKV and SC participated in data curation, formal analysis, funding acquisition, supervision, and writing—review and editing. All authors contributed to and have approved the final manuscript.
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Highlights
• Preclinical and clinical studies have demonstrated the contribution of blood-brain barrier (BBB) disruption to the pathogenesis and sequelae of MDD.
• Peripheral inflammation and neuroinflammation play critical roles in BBB disruption.
• Gut-brain axis might have a significant role in BBB integrity.
• The disruption of the BBB contributes to the complex interplay between depression and a myriad of medical comorbidities.
• COVID-19 has been reported to lead to BBB disruption and, as a result, to neuropsychiatric findings.
• To achieve antidepressant effects, novel therapeutic approaches that address BBB deficiencies can be promising.
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Varghese, S.M., Patel, S., Nandan, A. et al. Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04205-5
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DOI: https://doi.org/10.1007/s12035-024-04205-5