{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:44:14Z","timestamp":1782751454990,"version":"3.54.5"},"reference-count":26,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan Greece 2.0","award":["TAEDR-0541976"],"award-info":[{"award-number":["TAEDR-0541976"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Depressive disorders and obesity are highly comorbid conditions sharing genetic, metabolic, and immunological substrates. In a cross-sectional analysis of 53 participants across the obesity spectrum (lean n = 12; overweight n = 9; obese n = 32), a depression genetic risk score (d-GRS) correlated positively with BMI (\u03c1 = 0.379, p = 0.005) and with serum CRP (\u03c1 = 0.322, p = 0.031), consistent with the known genetic coarchitecture between depression and inflammatory traits. The d-GRS was tested against 116 flow-cytometry-derived immune parameters using Spearman rank correlation. The most consistent immune association at nominal significance (p &lt; 0.05, uncorrected) involved the immunoregulatory CD56brightCD16\u2212 natural killer (NK) cell subset across two independent gate representations (\u03c1 = 0.444, p = 0.004), remaining significant after sequential adjustment for BMI, sex, age, and physical activity (adjusted \u03c1 range: 0.439\u20130.469), with no equivalent association for a genetically independent obesity GRS. In silico analysis of d-GRS SNP-tagged genes identified several with documented roles in NK cell trafficking, activation, and cytokine production, providing a putative mechanistic basis for this association. These findings nominate the CD56brightCD16\u2212 NK cell subset as a candidate immunological link between depression genetic susceptibility and neuroimmune mechanisms, warranting independent replication and functional characterisation in prospective cohorts.<\/jats:p>","DOI":"10.3390\/cells15131179","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:27:37Z","timestamp":1782746857000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Risk for Depression Associates with Circulating Immunoregulatory Natural Killer Cells Independent of BMI: An Exploratory Immunophenotyping Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Aikaterini","family":"Fyka","sequence":"first","affiliation":[{"name":"Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-9147","authenticated-orcid":false,"given":"Dimitra","family":"Anastasopoulou","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Livadara","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6403-6761","authenticated-orcid":false,"given":"Aristides G.","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalliopi","family":"Gkouskou","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1001\/jamapsychiatry.2019.4188","article-title":"Shared Genetic Loci Between Body Mass Index and Major Psychiatric Disorders: A Genome-wide Association Study","volume":"77","author":"Bahrami","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41398-022-01783-7","article-title":"Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals","volume":"12","author":"Molina","year":"2022","journal-title":"Transl. 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