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or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population.<\/jats:p>","DOI":"10.3390\/metabo13070851","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T01:06:36Z","timestamp":1689555996000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8506-1122","authenticated-orcid":false,"given":"Nicole","family":"Prince","sequence":"first","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryl","family":"Stav","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Cote","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6345-008X","authenticated-orcid":false,"given":"Su H.","family":"Chu","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4262-2786","authenticated-orcid":false,"given":"Chirag M.","family":"Vyas","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia I.","family":"Okereke","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Nutrition, Harvard T. 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Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA"},{"name":"Geriatric Research Education Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0422-5875","authenticated-orcid":false,"given":"Augusto A","family":"Litonjua","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonary Medicine, Golisano Children\u2019s Hospital at Strong, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantel","family":"Vokonas","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Boston, MA 02114, USA"},{"name":"VA Normative Aging Study, VA Boston Healthcare System, Boston, MA 02130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs, Boston, MA 02114, USA"},{"name":"VA Normative Aging Study, VA Boston Healthcare System, Boston, MA 02130, USA"},{"name":"Department of Medicine, Boston University Chobanian and Avidisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4080-8621","authenticated-orcid":false,"suffix":"III","given":"Avron","family":"Spiro","sequence":"additional","affiliation":[{"name":"VA Normative Aging Study, VA Boston Healthcare System, Boston, MA 02130, USA"},{"name":"Department of Medicine, Boston University Chobanian and Avidisian School of Medicine, Boston, MA 02118, USA"},{"name":"Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA"},{"name":"Department of Psychiatry, Boston University Chobanian and Avidisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Lasky-Su","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-1822","authenticated-orcid":false,"given":"Rachel S.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"key":"ref_1","unstructured":"National Institute of Mental Health (2023, April 10). 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