{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:57:54Z","timestamp":1769839074829,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T00:00:00Z","timestamp":1395100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2014,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function:ANK<\/jats:styled-content>3<\/jats:italic>(rs10994336),BDNF<\/jats:styled-content><\/jats:italic>(rs6265),CACNA<\/jats:styled-content>1C<\/jats:italic>(rs1006737), andDGKH<\/jats:styled-content><\/jats:italic>(rs1170191).<\/jats:p><\/jats:sec>Aims<\/jats:title>The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto\u2010limbic regions implicated in affect regulation.<\/jats:p><\/jats:sec>Methods and materials<\/jats:title>Participants included 128 individuals with bipolar disorder (33% male, Mean age\u00a0=\u00a038.5), 48 with major depressive disorder (29% male, Mean age\u00a0=\u00a040.4), and 149 healthy controls (35% male, Mean age\u00a0=\u00a036.5). Genotypes were determined by 5\u2032\u2010fluorogenic exonuclease assays (T<\/jats:styled-content>aqMan\u00ae<\/jats:sup>). Fronto\u2010limbic volumes were obtained from high resolution brain images using Freesurfer. Chi\u2010square analyses, bivariate correlations, and mediational models examined relationships between genetic variants, mood diagnoses, cognitive measures, and brain volumes.<\/jats:p><\/jats:sec>Results<\/jats:title>Carriers of the minorBDNF<\/jats:styled-content><\/jats:italic>andANK<\/jats:styled-content>3<\/jats:italic>alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients (P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.047).CACNA<\/jats:styled-content>1C<\/jats:styled-content><\/jats:italic>minor allele carriers had larger bilateral caudate, insula, globus pallidus, frontal pole, and nucleus accumbens volumes (smallestr\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.13,P\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.043), and increasedIQ<\/jats:styled-content>(r\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.18,P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.001).CACNA<\/jats:styled-content>1C<\/jats:styled-content><\/jats:italic>associations with brain volumes andIQ<\/jats:styled-content>were independent; larger fronto\u2010limbic volumes did not mediate increasedIQ<\/jats:styled-content>. Other candidate variants were not significantly associated with diagnoses, cognition, or fronto\u2010limbic volumes.<\/jats:p><\/jats:sec>Discussion and conclusions<\/jats:title>CACNA<\/jats:styled-content>1C<\/jats:styled-content><\/jats:italic>may be associated with biological systems altered in mood disorder. Increases in fronto\u2010limbic volumes and cognitive ability associated withCACNA<\/jats:styled-content>1C<\/jats:styled-content><\/jats:italic>minor allele genotypes are congruent with findings in healthy samples and may be a marker for increased risk for neuropsychiatric phenotypes. Even larger multimodal studies are needed to quantify the magnitude and specificity of genetic\u2010imaging\u2010cognition\u2010symptom relationships.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.226","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T11:07:00Z","timestamp":1395140820000},"page":"418-430","source":"Crossref","is-referenced-by-count":26,"title":["Candidate gene associations with mood disorder, cognitive vulnerability, and fronto\u2010limbic volumes"],"prefix":"10.1002","volume":"4","author":[{"given":"Thomas W.","family":"Frazier","sequence":"first","affiliation":[{"name":"Centers for Autism and Pediatric Behavioral Health Cleveland Clinic Cleveland Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Youngstrom","sequence":"additional","affiliation":[{"name":"Departments of Psychology and Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian A.","family":"Frankel","sequence":"additional","affiliation":[{"name":"Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine and Michael E. DeBakey VA Medical Center Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana B.","family":"Zunta\u2010Soares","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences UT Center of Excellence on Mood Disorders University of Texas Medical School at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marsal","family":"Sanches","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences UT Center of Excellence on Mood Disorders University of Texas Medical School at Houston Houston Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Escamilla","sequence":"additional","affiliation":[{"name":"Center of Excellence in Neurosciences Texas Tech University Health Science Center El Paso Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine and Michael E. 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