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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Serum levels of chemokines in adolescents with major depression treated with fluoxetine
Francisco Rafael de la Peña, Carlos Cruz-Fuentes, Lino Palacios, Manuel Iván Girón-Pérez, Emilio Medina-Rivero, Maria Dolores Ponce-Regalado, Samantha Alvarez-Herrera, Gilberto Pérez-Sánchez, Enrique Becerril-Villanueva, José Luis Maldonado-García, María C Jiménez-Martínez, Lenin Pavón
Francisco Rafael de la Peña, Lino Palacios, Adolescent Clinic, Clinical Services, National Institute of Psychiatry, “Ramón de la Fuente”, Mexico City 14370, Mexico
Carlos Cruz-Fuentes, Department of Psychiatric Genetics, Clinical Research Branch, National Institute of Psychiatry, “Ramón de la Fuente”, Mexico City 14370, Mexico
Manuel Iván Girón-Pérez, Universidad Autónoma de Nayarit, Laboratorio de Inmunotoxicología, Boulevard Tepic-Xalisco s/n, Cd de la Cultura Amado Nervo, Tepic 63000, Mexico
Manuel Iván Girón-Pérez, Centro Nayarita de Innovación y Transferencia de Tecnología A.C. Laboratorio Nacional para la Investigación en Inocuidad Alimentaria-Unidad Nayarit, Calle Tres s/n. Cd Industrial, Tepic 63000, Nayarit, Mexico
Emilio Medina-Rivero, Unidad de Desarrollo e Investigación en Bioprocesos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Unidad Profesional Lázaro Cárdenas, Mexico City 11340, Mexico
Maria Dolores Ponce-Regalado, Departamento de Ciencias de Salud, Centro Universitario de los Altos, Universidad de Guadalajara Av Rafael Casillas Aceves No.1200, Tepatitlán de Morelos, Jalisco, 47610, Mexico
Samantha Alvarez-Herrera, Gilberto Pérez-Sánchez, Enrique Becerril-Villanueva, José Luis Maldonado-García, Lenin Pavón, Laboratory of Psychoimmunology, National Institute of Psychiatry, “Ramón de la Fuente”, Mexico City 14370, Mexico
María C Jiménez-Martínez, Department of Immunology and Research Unit, Institute of Ophthalmology “Conde de Valenciana Foundation”, Mexico City 06800, Mexico
María C Jiménez-Martínez, Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico
Author contributions: de la Peña FR, Cruz-Fuentes C, and Pavón L designed the study and wrote the protocol; de la Peña FR, Palacios L, Ponce-Regalado MD, Maldonado-García JL, Jiménez-Martínez MC, and Pavón L supervised the patients’ recruitment; Girón-Pérez MI, Medina-Rivero E, Ponce-Regalado MD, Alvarez-Herrera S, Pérez-Sánchez G, and Becerril-Villanueva E collected the biological samples and conducted the experimental determinations; Pavón L supervised the development of all experiments; Palacios L, Girón-Pérez MI, Medina-Rivero E, Ponce-Regalado MD, Alvarez-Herrera S, Pérez-Sánchez G, Becerril-Villanueva E, Maldonado-García JL, Jiménez-Martínez MC, and Pavón L analyzed the results; All authors approved the final manuscript.
Supported by Secretaria de Ciencia, Tecnología e Innovación, No. 0048/2014
Institutional review board statement: The study was reviewed and approved by the ethics committee of the Instituto Nacional de Psiquiatria “Ramón de la Fuente Muñiz” (México).
Conflict-of-interest statement: The authors report no conflicts of interest in relation to the topic of this study.
Data sharing statement: Data of the studies are not publicly available but might be shared upon request from the corresponding author.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lenin Pavón, PhD, Professor, Laboratory of Psychoimmunology, National Institute of Psychiatry, “Ramón de la Fuente”, Calzada México-Xochimilco 101, Colonia San Lorenzo Huipulco, Mexico City 14370, Mexico. lkuriaki@imp.edu.mx
Received: February 29, 2020
Peer-review started: February 29, 2020
First decision: April 29, 2020
Revised: May 31, 2020
Accepted: June 27, 2020
Article in press: June 27, 2020
Published online: August 19, 2020
ARTICLE HIGHLIGHTS
Research background
Major depressive disorder (MDD) affects 350 million people, approximately 6% of whom are adolescents; however, research on this age group is limited. The depressive symptomatology in adolescents can be confused with other psychiatric disorders, in turn affecting the proper diagnosis and normal development of patients. MDD in adolescents is associated with several negative outcomes including other psychiatric disorders later in life, educational impairment, self-injury, and suicide.
Research motivation
The immune system reaches maturity at about 16 years of age and upon the central nervous system second neural pruning. This makes adolescent patients with MDD have molecular characteristics that initially differ from adults and the elderly. These particularities have not been efficiently explored.
Research objectives
This study determined the differences in circulatory levels of eotaxin, interleukin (IL)-8, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α and MIP-1β in HVs and adolescents with MDD, and assessed the changes induced by antidepressants consumed during 8 wk of clinical follow-up, which is the minimum time to observe the therapeutic efficacy of selective serotonin reuptake inhibitors, like fluoxetine.
Research methods
We measured serum levels of eotaxin, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β in adolescents with MDD and performed a clinical psychiatric evaluation using the Hamilton depresión rating scale (HDRS). Eighteen HVs and twenty-two adolescents with MDD were monitored throughout 8 wk of clinical follow-up.
Research results
All evaluated chemokines decreased at 4 wk, but only MCP-1 and IL-8 differed significantly (P < 0.05) between 0 and 4 wk. In adolescents with MDD, all chemokines rose to their initial concentrations by 8 wk (vs 0 wk), but only IP-10 did so significantly (P < 0.05). All patients experienced a significant decrease in HDRS scores at 4 wk (P < 0.0001) and 8 wk (P < 0.0001) compared with 0 wk. Despite the consumption of fluoxetine, adolescents with MDD had significantly higher chemokines levels, even after considering the improvement in the HDRS score.
Research conclusions
Our results showed a significant elevation in serum chemokine levels in adolescents with MDD despite treatment with fluoxetine and an improvement in HDRS scores. This prompted us to consider the multidisciplinary management of MDD patients since high levels of MCP-1 and IP-10 are associated with coronary risk. The elevation detected in eotaxin, IP-10, and IL-8 serum levels might explain certain features of depressed patients such as impaired cognition, memory, and learning.
Research perspectives
Given the number of functions in which chemokines and their receptors are involved in the central nervous system, they could become novel diagnostic markers or therapeutic targets for MDD patients. However, a more significant number of studies are required, particularly in the adolescent population.
