{"doi":"10.1016/j.bbih.2025.100988","title":"HIV and Low Omega-3 Levels May Heighten Hippocampal Volume Differences Between Men and Women With Substance Use","abstract":"Background: Sex differences in hippocampal volumes are well-documented, but their interaction with HIV status and omega-3 fatty acids-particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-remains unclear, especially in underserved populations. This study examines how HIV and omega-3 fatty acids influence sex differences in hippocampal volume and explores whether cognitive performance related to episodic memory modifies the association of omega-3 levels with hippocampal volume, considering both HIV status and sex. Methods: We enrolled 166 participants aged over 45 years from a Baltimore, Maryland cohort. Brain MRIs were performed using a 3.0-T Siemens scanner, and volumetric segmentation was conducted with FreeSurfer (version 6.0), adjusting for intracranial volume (ICV). Results: Our study found that: (1) Among HIV-negative participants, females had significantly lower hippocampal volumes than males in 1 of 26 regions, whereas HIV-positive females had lower volumes in 13 of 26 regions (p < 0.006 for HIV-negative vs. HIV-positive females), (2) In HIV-positive individuals with EPA levels ≤0.40 %, females exhibited lower volumes in 11 of 26 regions, compared to no differences in those with EPA levels >0.40 % (p = 0.0003 for ≤0.40 % vs. >0.40 %), (3) Across all participants, lower EPA and DHA levels were associated with greater sex differences in hippocampal volumes, which diminished or disappeared at higher EPA and DHA levels (p < 0.00001 for EPA ≤0.40 % vs. >0.40 %; p = 0.004 for DHA ≤2.0 % vs. >2.0 %), and (4) Among Adults with lower episodic memory, higher log-scaled EPA levels were independently associated with greater hippocampal volume. Conclusions: HIV may amplify sex differences in hippocampal volumes, disproportionately affecting females. Higher EPA and DHA levels may mitigate these effects, suggesting a protective role against hippocampal atrophy. Further studies are warranted to confirm these findings and explore whether the benefits extend to males with HIV or individuals without HIV.","journal":"Brain Behavior & Immunity - Health","year":2025,"id":543664,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1079718,"name":"Jiachen Zhuo","orcid":"0000-0001-6637-701X","position":1,"is_corresponding":false},{"id":739956,"name":"Glenn J. Treisman","orcid":"0000-0003-4578-6150","position":2,"is_corresponding":false},{"id":298317,"name":"Gary Gerstenblith","orcid":"0000-0001-6046-6812","position":3,"is_corresponding":false},{"id":604703,"name":"David D. Celentano","orcid":"0000-0002-6472-7706","position":4,"is_corresponding":false},{"id":291970,"name":"Yihong Yang","orcid":"0000-0002-1035-5038","position":5,"is_corresponding":false},{"id":397555,"name":"Betty Jo Salmeron","orcid":"0000-0003-1699-9333","position":6,"is_corresponding":false},{"id":291966,"name":"Hong Gu","orcid":"0000-0001-6496-0383","position":7,"is_corresponding":false},{"id":426731,"name":"Thorsten M. Leucker","orcid":"0000-0003-2569-6617","position":8,"is_corresponding":false},{"id":1433655,"name":"Xiao Liang","orcid":"0000-0001-5476-8304","position":9,"is_corresponding":false},{"id":426538,"name":"Raúl N. Mandler","orcid":"0000-0002-3320-5374","position":10,"is_corresponding":false},{"id":371462,"name":"Jag Khalsa","orcid":"0000-0002-6534-3616","position":11,"is_corresponding":false},{"id":1433656,"name":"Óscar Peña‐Nogales","orcid":"0000-0001-7364-9335","position":12,"is_corresponding":false},{"id":787526,"name":"Shaoguang Chen","orcid":null,"position":13,"is_corresponding":false},{"id":585886,"name":"Shenghan Lai","orcid":"0000-0003-1340-9609","position":14,"is_corresponding":false},{"id":267745,"name":"Elana Rosenthal","orcid":"0000-0001-7234-4871","position":15,"is_corresponding":false},{"id":721330,"name":"Karl Goodkin","orcid":null,"position":16,"is_corresponding":false},{"id":284524,"name":"Vincent A. 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