Inflammation and immune system pathways as biological signatures of adolescent depression-the IDEA-RiSCo study

Valentina Zonca, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK. valentina.zonca@unimi.it.
Moira Marizzoni, Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Via Pilastroni, 4, 25125, Brescia, Italy.
Samantha Saleri, Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Via Pilastroni, 4, 25125, Brescia, Italy.
Zuzanna Zajkowska, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Pedro H. Manfro, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350-400N, Porto Alegre, RS, 90035-903, Brazil.
Laila Souza, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350-400N, Porto Alegre, RS, 90035-903, Brazil.
Anna Viduani, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350-400N, Porto Alegre, RS, 90035-903, Brazil.
Luca Sforzini, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Johnna R. Swartz, Department of Human Ecology, University of California, Davis, Davis, CA, 95616, USA.
Helen L. Fisher, King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
Brandon A. Kohrt, Center for Global Mental Health Equity, Department of Psychiatry and Behavioral Health, School of Medicine and Health Sciences, The George Washington University, 2120 L St NW, Ste 600, Washington, DC, 20037D, USA.
Christian Kieling, Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Child & Adolescent Psychiatry Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350-400N, Porto Alegre, RS, 90035-903, Brazil.
Marco Andrea Riva, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Annamaria Cattaneo, Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Valeria Mondelli, King's College London, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, London, UK.

Document Type

Journal Article

Publication Date

6-1-2024

Journal

Translational psychiatry

Volume

14

Issue

1

DOI

10.1038/s41398-024-02959-z

Abstract

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.

Department

Psychiatry and Behavioral Sciences

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