{"doi":"10.1016/j.bbih.2023.100666","title":"Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial","abstract":"Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m2, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = −0.35, p = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = −0.07, p = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms (Ρ = .71, p = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.","journal":"Brain Behavior & Immunity - Health","year":2023,"id":344642,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320517,"name":"David Mischoulon","orcid":"0000-0001-7233-5860","position":1,"is_corresponding":false},{"id":58339,"name":"Boadie W. Dunlop","orcid":"0000-0002-4653-0483","position":2,"is_corresponding":false},{"id":320519,"name":"Becky Kinkead","orcid":"0000-0003-0169-6989","position":3,"is_corresponding":false},{"id":320520,"name":"Pamela J. Schettler","orcid":"0000-0002-0700-2119","position":4,"is_corresponding":false},{"id":598337,"name":"Richard T. Liu","orcid":"0000-0002-1367-9716","position":5,"is_corresponding":false},{"id":323420,"name":"Olivia I. Okereke","orcid":"0000-0002-9523-2693","position":6,"is_corresponding":false},{"id":320515,"name":"Stefania Lamon‐Fava","orcid":"0000-0002-8675-8159","position":7,"is_corresponding":false},{"id":287653,"name":"Maurizio Fava","orcid":"0000-0002-4635-0458","position":8,"is_corresponding":false},{"id":320522,"name":"Mark Hyman Rapaport","orcid":"0000-0001-8359-987X","position":9,"is_corresponding":false},{"id":1083472,"name":"Naoise Mac Giollabhui","orcid":"0000-0003-4226-5704","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:11:35.133818Z","pmid":"37503359","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}