{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:44:45Z","timestamp":1767357885757,"version":"3.48.0"},"reference-count":55,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Treatment-resistant depression (TRD) is a subtype of major depressive disorder (MDD) that fails to respond to first-line pharmacotherapy. This cross-sectional study compared blood concentrations of folic acid, vitamin B12, and homocysteine between female depressed patients with or without TRD, and examined the association of these parameters with the severity of depression. It included 116 female patients treated for MDD, of whom 59 (51%) developed TRD. The diagnosis of MDD was established via a structured clinical interview, while the severity of depression was measured with the Montgomery\u2013Asberg Depression Rating Scale. Blood samples were taken at the initial psychiatric examination to determine the serum levels of folic acid and vitamin B12 and plasma levels of homocysteine. Folic acid levels were significantly lower in the female TRD group (p &lt; 0.001), whereas homocysteine levels were significantly higher in the female TRD group (p &lt; 0.001), compared to the female depressed group without TRD. In the regression analyses, higher levels of homocysteine (p &lt; 0.001) were associated with TRD, while lower levels of folic acid (p = 0.036) were related to higher severity of depression, independently of sociodemographic and clinical parameters. Our findings showed that folate correlated with symptom severity, while homocysteine correlated with the TRD status in female MDD patients.<\/jats:p>","DOI":"10.3390\/biom16010070","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood Concentrations of Folic Acid and Homocysteine Are Associated with Treatment-Resistant Depression Among Female Depressed Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Iva","family":"Rado\u0161","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zrinka","family":"Vuksan-\u0106usa","sequence":"additional","affiliation":[{"name":"Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-2857","authenticated-orcid":false,"given":"Jakov","family":"Mili\u0107","sequence":"additional","affiliation":[{"name":"Catholic Faculty of Theology, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-2181","authenticated-orcid":false,"given":"Marina","family":"\u0160agud","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Lon\u010dar Vran\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nenad","family":"Jak\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjanka","family":"Vuksan-\u0106usa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychological Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia"},{"name":"School of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nela","family":"Pivac","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia"},{"name":"Department of Psychiatric Investigations, University Psychiatric Hospital Vrapce, 10090 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2147\/NDT.S198774","article-title":"Management of Treatment-Resistant Depression: Challenges and Strategies","volume":"16","author":"Voineskos","year":"2020","journal-title":"Neuropsychiatr. 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