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The Role of Omega-3 Fatty Acids in Depression: From Biological Mechanisms to Clinical Targets

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Dr. Annamaria Cattaneo

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1. Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy
2. Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy
Interests: mental health; psychiatric disorder; major depressive disorder; perinatal depression; stress; gut microbiota; neurodevelopmental disorders; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

This Special Issue examines how omega-3 fatty acids shape depressive pathology, surveying both mechanistic underpinnings and clinical advances. Although evidence for clinical benefit is growing, key questions remain regarding causal pathways, optimal formulations and dosing, patient stratification, and the role of adjunctive use alongside standard treatments.

We welcome contributions that move beyond single pathways to integrate central and peripheral inflammation, the gut–brain axis, neurovascular function and synaptic plasticity, cellular bioenergetics, and neuroendocrine regulation (HPA axis). Submissions may include original research, reviews, and perspectives across basic, clinical, and translational research.

By integrating these lines of evidence, the Special Issue aims to clarify the therapeutic potential of omega-3 fatty acids in depression and to chart a path toward mechanism-guided, patient-tailored interventions.

Dr. Annamaria Cattaneo
Guest Editor

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19 pages, 1440 KB

Open AccessArticle

Elevated Depressive Symptoms Shape Gut Barrier Integrity, LPS Translocation, and PUFA Composition in IBS-D: Evidence from a Low-FODMAP Dietary Intervention

by Laura Prospero, Michele Linsalata, Giuseppe Riezzo, Antonella Orlando, Antonia Ignazzi, Benedetta D’Attoma, Domenica Mallardi, Maria Notarnicola, Valeria Tutino, Valentina De Nunzio, Giuliano Pinto and Francesco Russo

Nutrients 2026, 18(9), 1473; https://doi.org/10.3390/nu18091473 - 5 May 2026

Viewed by 493

Abstract

Introduction: Alterations of the microbiota–gut–brain axis, including increased intestinal permeability (IP), changes in microbial activity, and immune activation, are central to the pathophysiology of irritable bowel syndrome with diarrhea (IBS-D). The low-fermentable oligo-di-monosaccharides and polyols (FODMAP) diet (LFD) is an established therapy for IBS, yet its systemic effects, particularly in patients with elevated depressive symptoms, remain incompletely characterized. Methods: This single-arm pre–post study investigated associations between depressive symptom severity and markers of small IP (s-IP), endotoxin exposure, inflammation, and erythrocyte membrane polyunsaturated fatty acid (PUFA) composition in 43 IBS-D patients undergoing a 12-week personalized LFD. Patients were classified using the Symptom Checklist-90-Revised depression subscale into those with (d+, n = 23) and without (d−, n = 20) clinically elevated depressive symptoms. Results: At baseline, d+ patients exhibited higher s-IP, circulating lipopolysaccharide levels, inflammatory markers, and a more pro-inflammatory PUFA profile. Following LFD, significant improvements in symptoms and several biological parameters were observed in the overall cohort. Greater absolute changes in d+ patients were consistent with their higher baseline values rather than indicating differential responsiveness. Baseline depressive symptoms were not significantly associated with the magnitude of post-intervention changes in IP or inflammatory markers. Conclusions: These findings suggest that elevated depressive symptoms identify an IBS-D subgroup characterized by greater baseline biological burden. Results should be interpreted as associative given the single-arm design, absence of a control group, and the concurrent reduction in body weight, which may have influenced the observed changes. Randomized controlled studies are needed to clarify the role of dietary interventions in modulating gut–brain axis-related pathways in IBS-D. Full article

(This article belongs to the Special Issue The Role of Omega-3 Fatty Acids in Depression: From Biological Mechanisms to Clinical Targets)

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15 pages, 2987 KB

Open AccessEditor’s ChoiceArticle

Altered Plasma Endocannabinoids and Oxylipins in Adolescents with Major Depressive Disorders: A Case–Control Study

by Akash Chakravarty, Abinaya Sreetharan, Ester Osuna, Isabelle Herter-Aeberli, Isabelle Häberling, Jeannine Baumgartner, Gregor E. Berger and Martin Hersberger

Nutrients 2026, 18(2), 280; https://doi.org/10.3390/nu18020280 - 15 Jan 2026

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Abstract

Background: Pediatric Major Depressive Disorder (pMDD) is one of the leading causes of disability in adolescents. There is currently no single explanation that fully accounts for the cause of the disorder, but various factors, including dysregulation of the immune and stress responses, have been linked to its onset. Oxylipins and endocannabinoids, derived from metabolization of n-3 and n-6 polyunsaturated fatty acids (PUFAs), regulate inflammation and have been suggested to attenuate inflammation associated with depression. This study aims to understand whether adolescents with pMDD have altered baseline levels of oxylipins and endocannabinoids compared to healthy adolescents. Methods: In this case–control study, we measured 60 oxylipins and endocannabinoids in plasma from 82 adolescents with pMDD and their matching healthy controls. Results: A Principal Component Analysis revealed substantial variability within each group and only a moderate degree of separation between them. In a paired analysis, the lipid mediators of controls exhibited higher concentrations of n-6 PUFA-derived prostaglandins and thromboxanes (PGE2, PGD2, PGF2a and TXB2), n-3 PUFA-derived TxB3, and the endocannabinoids AEA, EPEA, and DHEA. In contrast, cases had higher concentrations of the n-6 PUFA-derived 6-keto-PGF1a and the n-3 PUFA-derived PGD3. In addition, we observed a higher percentage of oxylipins and endocannabinoids derived from DHA (5.65 ± 5.46% vs. 4.72 ± 4.94%) and AA (16.31 ± 11.10% vs. 12.76 ± 13.46%) in plasma from controls, in line with the higher DHA and AA levels observed in erythrocytes from controls compared to cases. Conclusions: Overall, our results show lower plasma levels of endocannabinoids and lower DHA- and AA-derived oxylipins in adolescents with pMDD, supporting their role in the pathophysiology of pMDD. To infer a causative role of the n-3 and n-6 PUFA-derived oxylipins and endocannabinoids in pMDD, an intervention study with n-3 PUFA supplementation and monitoring of oxylipins and endocannabinoids would be necessary. Full article

(This article belongs to the Special Issue The Role of Omega-3 Fatty Acids in Depression: From Biological Mechanisms to Clinical Targets)

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