The role of the gut-brain axis in depression: endocrine, neural, and immune pathways
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The role of the gut-brain axis in depression: endocrine, neural, and immune pathways Anastasios P. Makris 1 & Minois Karianaki 1 & Konstantinos I. Tsamis 1,2 & Stavroula A. Paschou 1,3 Received: 14 March 2020 / Accepted: 30 July 2020 # Hellenic Endocrine Society 2020
Abstract The aim of this article is to summarize the pathways connecting the gut and the brain and to highlight their role in the development of depression as well as their potential use as therapeutic targets. A literature search was conducted in PubMed using relevant keywords and their combinations up to the end of March 2020. Previously seen as a disease pertaining solely to the central nervous system, depression is now perceived as a multifactorial condition that extends beyond neurotransmitter depletion. Central to our understanding of the disease is our current knowledge of the communication between the gut and the brain, which is bidirectional and involves neural, endocrine, and immune pathways. This communication is facilitated via stress-mediated activation of the HPA axis, which stimulates the immune system and causes a decrease in microbial diversity, also known as dysbiosis. This change in the intestinal flora leads, in turn, to bacterial production of various substances which stimulate both the enteric nervous system and the vagal afferents and contribute to additional activation of the HPA axis. Concomitantly, these substances are associated with an increase in intestinal permeability, namely, the leaky gut phenomenon. The bidirectional link between the gut and the brain is of great importance for a more inclusive approach to the management of depression. It can thus be deployed for the development of novel therapeutic strategies against depression, offering promising alternatives to limited efficacy antidepressants, while combination therapy also remains a potential treatment option. Keywords Gut-brain axis . Gut microbiota . Depression . Psychological stress . Probiotics
Introduction According to the World Health Organization (WHO), depression is a leading cause of disability, affecting approximately 300 million people worldwide with an increasing trend [1]. It is characterized by symptoms of depressed mood, anhedonia, feelings of guilt and worthlessness, and sleep and appetite disturbances [2]. Despite its very high prevalence, depression often lacks both diagnosis and treatment, largely due to a combination of stigma, ineffective treatment, and insufficient funding [3]. As a result, efforts are being made to understand depression in a wider context, extending further than merely to neurobiochemical changes [1]. Moreover, pharmacological * Stavroula A. Paschou [email protected] 1
School of Medicine, European University Cyprus, Nicosia, Cyprus
2
School of Medicine, University of Ioannina, Ioannina, Greece
3
School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
therapy for depression is effective at a percentage of 74%, even in combinations [1]. As a result, the ineffectiveness of
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