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A single-nucleotide polymorphism (SNP) in <jats:italic>PCLO<\/jats:italic>, rs2522833, is thought to affect protein stability and the activity of the hypothalamic\u2013pituitary\u2013adrenal axis. We investigated the relationship between cortical volume and this SNP in first-episode, drug-naive patients with MDD or healthy control subjects. Seventy-eight participants, including 30 patients with MDD and 48 healthy control subjects, were recruited via interview. <jats:italic>PCLO<\/jats:italic> rs2522833 genotyping and plasma cortisol assays were performed, and gray matter volume was estimated using structural magnetic resonance images. Among the individuals carrying the C-allele of <jats:italic>PCLO<\/jats:italic> rs2522833, the volume of the left temporal pole was significantly smaller in those with MDD than in healthy controls (family-wise error-corrected, <jats:italic>P<\/jats:italic>=0.003). No differences were detected in other brain regions. In addition, the C-carriers showed a larger volume reduction in the left temporal pole than those in the individuals with A\/A genotype (<jats:italic>P<\/jats:italic>=0.0099). Plasma cortisol levels were significantly higher in MDD-affected C-carriers than in the healthy control C-carriers (12.76\u00b16.10 vs 9.31\u00b13.60\u2009n<jats:sc>m<\/jats:sc>, <jats:italic>P<\/jats:italic>=0.045). We conclude that <jats:italic>PCLO<\/jats:italic> SNP rs2522833 is associated with a gray matter volume reduction in the left temporal pole in drug-naive, first-episode patients with MDD carrying the C-allele.<\/jats:p>","DOI":"10.1038\/tp.2017.100","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T13:41:00Z","timestamp":1496151660000},"page":"e1140-e1140","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["PCLO rs2522833-mediated gray matter volume reduction in patients with drug-naive, first-episode major depressive disorder"],"prefix":"10.1038","volume":"7","author":[{"given":"R","family":"Igata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Katsuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Kakeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Igata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Konishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Atake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Kawasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Korogi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,5,30]]},"reference":[{"key":"BFtp2017100_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jad.2014.04.002","volume":"164","author":"A Szczepankiewicz","year":"2014","unstructured":"Szczepankiewicz A, Leszczynska-Rodziewicz A, Pawlak J, Narozna B, Rajewska-Rager A, Wilkosc M et al. 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