{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:48:55Z","timestamp":1782924535624,"version":"3.54.5"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Depressive disorders are a leading cause of global disability, yet gene expression studies in Middle Eastern populations remain scarce. This study investigated peripheral blood expression of seven candidate genes, previously identified in animal models and early-onset depression, in adults with and without depressive disorders in United Arab Emirates (UAE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a case-control design, 49 adults with depressive disorders (ICD-10 major depressive disorder, dysthymia, or adjustment disorder with depressed features) and 49 non-depressed controls were assessed with the Beck Depression Inventory-II and Patient Health Questionnaire-9. Peripheral blood expression of ADCY3, DGKA, FAM46A, CADM1, KIAA1539, MARCKS, and RAPH1 was measured by quantitative real-time PCR, normalised to GAPDH. Analyses included Mann-Whitney U tests, principal component analysis, fold-change estimation, pre-specified receiver operating characteristic analysis, and severity-restricted, age-balanced, and RNA-quality sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CADM1 showed modest upregulation in the depressive disorder group (1.30-fold; Mann-Whitney p = 0.049, uncorrected) that did not survive multiple testing correction (Benjamini-Hochberg p = 0.178). Principal component analysis revealed an unadjusted PC2 difference (p = 0.006), driven by CADM1 and RAPH1, that attenuated after age adjustment (MANCOVA p = 0.156). CADM1 correlated negatively with depression severity (BDI-II \u03c1 = \u22120.280, p = 0.005), and the signal strengthened monotonically across severity strata (moderate-severe BDI-II \u2265 20, p = 0.029; severe BDI-II \u2265 29, p = 0.014), arguing against diagnostic heterogeneity as the primary driver. However, propensity score matching on age abolished the CADM1 effect (p = 0.965). Exploratory subgroup analyses suggested sex-specific patterns (CADM1 in males, p = 0.039; KIAA1539 in females, p = 0.010). The CADM1 area under the receiver operating characteristic curve was 0.616, indicating no diagnostic utility.\n                      <jats:italic>Post-hoc<\/jats:italic>\n                      power for individual genes was 5\u201319%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This pilot provides the first peripheral blood gene expression data for depression in a UAE population. Given the small sample, the 13-year mean age difference between groups, and unmeasured confounders, CADM1 is best framed as a hypothesis-generating candidate only; the signal was unstable after age balancing and the discrimination performance (AUC\u00a0=\u00a00.616) is below any clinically useful threshold. Validation in larger, strictly age-matched studies is required before any clinical interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1850124","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:53:53Z","timestamp":1782921233000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral blood CADM1 expression and multi-gene signatures in depressive disorders: a pilot case-control study from the United Arab Emirates"],"prefix":"10.3389","volume":"17","author":[{"given":"Rukhsana","family":"Nawaz","sequence":"first","affiliation":[{"name":"Department of Clinical Psychology, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Al Awadhi","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadwa","family":"Al Mughairbi","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Emergency Health, Fatima College of Health Sciences","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Psychology, College of Medicine, Ajman University","place":["Ajman, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Ali","family":"Bokhari","sequence":"additional","affiliation":[{"name":"Al Amal Psychiatric Hospital, Emirates Health Services","place":["Dubai, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Fahad","family":"Javaid","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdalla A. R. M.","family":"Hamid","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B2","first-page":"1","volume-title":"The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR)","year":"2022"},{"key":"B3","volume-title":"Depression and other common mental disorders: global health estimates","year":"2017"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.14m09298","article-title":"The economic burden of adults with major depressive disorder in the United States (2005 and 2010)","volume":"76","author":"Greenberg","year":"2015","journal-title":"J Clin Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-publhealth-031912-114409","article-title":"The epidemiology of depression across cultures","volume":"34","author":"Kessler","year":"2013","journal-title":"Annu Rev Public Health"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001547","article-title":"Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010","volume":"10","author":"Ferrari","year":"2013","journal-title":"PloS Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/HRP.0000000000000054","article-title":"Genetic determinants of depression: recent findings and future directions","volume":"23","author":"Dunn","year":"2015","journal-title":"Harvard Rev Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291701003907","article-title":"Genetic risk factors for major depression in men and women: similar or different heritabilities and same or partly distinct genes","volume":"31","author":"Kendler","year":"2001","journal-title":"Psychol Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.157.10.1552","article-title":"Genetic epidemiology of major depression: review and meta-analysis","volume":"157","author":"Sullivan","year":"2000","journal-title":"AJP"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0326-7","article-title":"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions","volume":"22","author":"Howard","year":"2019","journal-title":"Nat Neurosci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0090-3","article-title":"Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression","volume":"50","author":"Wray","year":"2018","journal-title":"Nat Genet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.biopsych.2017.01.021","article-title":"Replicable and coupled changes in innate and adaptive immune gene expression in two case-control studies of blood microarrays in major depressive disorder","volume":"83","author":"Leday","year":"2018","journal-title":"Biol Psychiatry"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2014.66","article-title":"Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy","volume":"4","author":"Redei","year":"2014","journal-title":"Transl Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2012.26","article-title":"Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression","volume":"2","author":"Pajer","year":"2012","journal-title":"Transl Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/nyas.12748","article-title":"Blood transcriptomic markers for major depression: from animal models to clinical settings","volume":"1344","author":"Redei","year":"2015","journal-title":"Ann N Y Acad Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11920-015-0601-1","article-title":"The promise of biomarkers in diagnosing major depression in primary care: the present and future","volume":"17","author":"Redei","year":"2015","journal-title":"Curr Psychiatry Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.04.165","article-title":"Impairment of social and emotional behaviors in Cadm1-knockout mice","volume":"396","author":"Takayanagi","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.10.107","article-title":"Mutations in the gene encoding CADM1 are associated with autism spectrum disorder","volume":"377","author":"Zhiling","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1012778","article-title":"G\u03b1s, adenylyl cyclase, and their relationship to the diagnosis and treatment of depression","volume":"13","author":"Schappi","year":"2022","journal-title":"Front Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.neuron.2005.08.027","article-title":"Essential role for the PKC target MARCKS in maintaining dendritic spine morphology","volume":"48","author":"Calabrese","year":"2005","journal-title":"Neuron"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.5001\/omj.2021.89","article-title":"Genetic biomarkers in association with depressive disorder in UAE residents: a pilot case study","volume":"36","author":"Mahmood","year":"2021","journal-title":"Oman Med J"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62189-3","article-title":"The state of health in the Arab world, 1990\u20132010: an analysis of the burden of diseases, injuries, and risk factors","volume":"383","author":"Mokdad","year":"2014","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1207\/s15327752jpa6703_13","article-title":"Comparison of Beck Depression Inventories-IA and-II in psychiatric outpatients","volume":"67","author":"Beck","year":"1996","journal-title":"J Pers Assess"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256363","article-title":"The PHQ-9: validity of a brief depression severity measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J Gen Intern Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2008.06.026","article-title":"The PHQ-8 as a measure of current depression in the general population","volume":"114","author":"Kroenke","year":"2009","journal-title":"J Affect Disord"},{"key":"B26","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12991-017-0155-1","article-title":"An arabic translation, reliability, and validation of Patient Health Questionnaire in a Saudi sample","volume":"16","author":"AlHadi","year":"2017","journal-title":"Ann Gen Psychiatry"},{"key":"B27","volume-title":"Manual of the Arabic BDI-II","author":"Ghareeb","year":"2000"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256363","article-title":"Development of primer-special TaqMan PCR: a novel SNP detection method to detect CYP2C9 3 in South Chinese","volume":"14","author":"Qiu","year":"2010","journal-title":"Mol Diagn Ther"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072356","article-title":"SynCAM, a synaptic adhesion molecule that drives synapse assembly","volume":"297","author":"Biederer","year":"2002","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ng.686","article-title":"Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index","volume":"42","author":"Speliotes","year":"2010","journal-title":"Nat Genet"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4386","article-title":"Sex-specific transcriptional signatures in human depression","volume":"23","author":"Labont\u00e9","year":"2017","journal-title":"Nat Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin Chem"},{"key":"B34","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.jad.2017.08.087","article-title":"Transcriptomic and epigenomic biomarkers of antidepressant response","volume":"233","author":"Belzeaux","year":"2018","journal-title":"J Affect Disord"},{"key":"B35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.neulet.2016.12.071","article-title":"DNA methylation and clinical response to antidepressant medication in major depressive disorder: a review and recommendations","volume":"669","author":"Lisoway","year":"2018","journal-title":"Neurosci Lett"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.57","article-title":"Gene expression in major depressive disorder","volume":"21","author":"Jansen","year":"2016","journal-title":"Mol Psychiatry"},{"key":"B37","doi-asserted-by":"publisher","first-page":"8570","DOI":"10.1038\/ncomms9570","article-title":"The transcriptional landscape of age in human peripheral blood","volume":"6","author":"Peters","year":"2015","journal-title":"Nat Commun"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217154110","article-title":"Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome","volume":"110","author":"M\u00f6ller-Levet","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B39","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s13353-013-0173-x","article-title":"Reference genes in real-time PCR","volume":"54","author":"Kozera","year":"2013","journal-title":"J Appl Genet"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2024.1422939","article-title":"Omics approaches open new horizons in major depressive disorder: from biomarkers to precision medicine","volume":"15","author":"Stolfi","year":"2024","journal-title":"Front Psychiatry"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01806-1","article-title":"Molecular pathways of major depressive disorder converge on the synapse","volume":"28","author":"Fries","year":"2023","journal-title":"Mol Psychiatry"},{"key":"B43","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s13073-021-01003-9","article-title":"Genomic medicine in the Middle East","volume":"13","author":"Abou Tayoun","year":"2021","journal-title":"Genome Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000530619","article-title":"Population genome programs across the Middle East and North Africa: successes, challenges, and future directions","volume":"8","author":"Ateia","year":"2023","journal-title":"BioMed Hub"},{"key":"B45","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41398-023-02724-8","article-title":"Integrative omics analysis reveals epigenomic and transcriptomic signatures underlying brain structural deficits in major depressive disorder","volume":"14","author":"Zheng","year":"2024","journal-title":"Transl Psychiatry"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1850124\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:53:54Z","timestamp":1782921234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1850124\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":45,"alternative-id":["10.3389\/fpsyt.2026.1850124"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1850124","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1850124"}}