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Ann N Y Acad Sci. 2019 Feb;1437(1):57-67. doi: 10.1111/nyas.13712. Epub 2018 May 11.

Inflammation in psychiatric disorders: what comes first?

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Laboratory of Stress Immunology, School of Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
National Institute of Science and Technology - Neuroimmunomodulation (INCT-NIM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, Brazil.
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas.


Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric disorders exhibit all cardinal features of inflammation, including increased circulating levels of inflammatory inducers, activated sensors, and inflammatory mediators targeting all tissues. Inflammation may contribute to the pathophysiology and clinical progression of these disorders. Of note, proinflammatory cytokines modulate mood behavior and cognition by reducing brain monoamine levels, activating neuroendocrine responses, promoting excitotoxicity (increased glutamate levels), and impairing brain plasticity. What are the sources of this chronic inflammation? Increasing evidence indicates that changes in neuroendocrine regulation, metabolism, diet/microbiota, and negative health behaviors are important triggers of inflammation. Finally, recent data indicate that early-life stress is associated with overt inflammation prior to the development of neuropsychiatric disorders.


HPA axis; cortisol; cytokines; inflammation; mood disorders; psychosocial stress


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