{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:59:11Z","timestamp":1785308351400,"version":"3.55.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Major depressive disorder (MDD) is a leading cause of disability; however, its neurogenetic mechanisms remain partially understood. Comparative genomic approaches reveal evolutionarily conserved risk factors, particularly when applied to ecologically valid models.\n                      <jats:italic>Lycaon pictus<\/jats:italic>\n                      is a social carnivore whose affiliative behavior has been shaped by natural selection. Since impaired social and affiliative function are a feature of depression, genes selected for social function in this species may serve as candidates for the social-affective dimension of MDD. Here, a comparative approach was integrated with human neuroimaging\u2013genetic analysis, focusing on white matter phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole-genome sequencing data from\n                      <jats:italic>Lycaon pictus<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f7) and\n                      <jats:italic>Canis lupus<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f36) were analyzed alongside a human cohort of 367 patients with MDD and 161 healthy controls using rare variant association tests. Across analyses,\n                      <jats:italic>ADAMTS18<\/jats:italic>\n                      emerged as a convergent gene of interest. Whole-exome sequencing and diffusion tensor imaging (DTI) were conducted on 234 patients with MDD and 135 healthy controls. Eleven common SNPs within\n                      <jats:italic>ADAMTS18<\/jats:italic>\n                      were examined for genotype-by-diagnosis and genotype-by-symptom interactions using tract-based DTI metrics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SNP rs11643211 showed a nominal genotype \u00d7 diagnosis interaction on axial diffusivity in the bilateral uncinate fasciculus, with elevated values in A allele carriers with MDD. In symptom-based models, rs1948719 was nominally associated with depression severity in the left cingulum\u2013cingulate gyrus. Although these associations did not survive false discovery rate correction, the nominal effects appeared to cluster within tracts implicated in affective integration and self-referential cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The present study is hypothesis-generating and identifies\n                      <jats:italic>ADAMTS18<\/jats:italic>\n                      as a gene worth further study in relation to white matter and depression. Cross-species neurogenomics may offer a useful framework for investigating links among social behavior, genetic variation and psychiatric vulnerability. However, given the small sample sizes and the absence of FDR-significant results, these findings should be interpreted as providing an exploratory framework for identifying candidate markers relevant to MDD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1878769","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:01:57Z","timestamp":1785304917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ADAMTS18 as a candidate gene linking social stress and depression: a cross-species study in African wild dogs (Lycaon pictus) and humans"],"prefix":"10.3389","volume":"20","author":[{"given":"Jihoon","family":"Park","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Gwan","family":"Jeon","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University","place":["Incheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youbin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Korea University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Man","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Asan Medical Center","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ryung","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University","place":["Incheon, Republic of Korea"]},{"name":"Institute for New Drug Development, College of Life Science and Bioengineering, Incheon National University","place":["Incheon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Joo","family":"Ham","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1089\/brain.2011.0071","article-title":"Characterization of cerebral white matter properties using quantitative magnetic resonance imaging stains","volume":"1","author":"Alexander","year":"2011","journal-title":"Brain Connect."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"31493","DOI":"10.1074\/jbc.R109.052340","article-title":"A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms","volume":"284","author":"Apte","year":"2009","journal-title":"J. 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