Candidate gene associations with mood disorder, cognitive vulnerability, and fronto‐limbic volumes. Issue 3 (18th March 2014)

• Record Type: Journal Article
• Authors: Frazier, Thomas W.; Youngstrom, Eric A.; Frankel, Brian A.; Zunta‐Soares, Giovana B.; Sanches, Marsal; Escamilla, Michael; Nielsen, David A.; Soares, Jair C.
• Is Part Of: Brain and behavior. Volume 4:Issue 3(2014:May)
• Page Start: 418
• Page End: 430
• Publication Date: 2014-03-18
• Subjects: Neurology -- Periodicals; Neurosciences -- Periodicals; Psychology -- Periodicals; Psychiatry -- Periodicals; 616.8005
• DOI: 10.1002/brb3.226
• Languages: English
• ISSNs: 2162-3279

Abstract

<abstract abstract-type="main" id="brb3226-abs-0001"> <title>Abstract</title> <sec id="brb3226-sec-0001" sec-type="section"> <title>Background</title> <p>Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function: <italic>ANK3</italic> (rs10994336), <italic>BDNF</italic> (rs6265), <italic>CACNA1C</italic> (rs1006737), and <italic>DGKH</italic> (rs1170191).</p> </sec> <sec id="brb3226-sec-0002" sec-type="section"> <title>Aims</title> <p>The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto‐limbic regions implicated in affect regulation.</p> </sec> <sec id="brb3226-sec-0003" sec-type="section"> <title>Methods and materials</title> <p>Participants included 128 individuals with bipolar disorder (33% male, Mean age = 38.5), 48 with major depressive disorder (29% male, Mean age = 40.4), and 149 healthy controls (35% male, Mean age = 36.5). Genotypes were determined by 5′‐fluorogenic exonuclease assays (TaqMan<sup>®</sup>). Fronto‐limbic volumes were obtained from high resolution brain images using Freesurfer. Chi‐square analyses, bivariate correlations, and mediational models examined relationships between genetic variants, mood diagnoses, cognitive measures, and brain volumes.</p> </sec> <sec id="brb3226-sec-0004" sec-type="section"> <title>Results</title> <p>Carriers of the minor <italic>BDNF</italic> and <italic>ANK3</italic> alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients (<italic>P </italic>=<italic> </italic>0.047). <italic>CACNA1C</italic> minor allele carriers had larger bilateral caudate, insula, globus pallidus, frontal pole, and nucleus accumbens volumes (smallest <italic>r </italic>=<italic> </italic>0.13, <italic>P </italic>=<italic> </italic>0.043), and increased IQ (<italic>r </italic>=<italic> </italic>0.18, <italic>P </italic><<italic> </italic>0.001). <italic>CACNA1C</italic> associations with brain volumes and IQ were independent; larger fronto‐limbic volumes did not mediate increased IQ. Other candidate variants were not significantly associated with diagnoses, cognition, or fronto‐limbic volumes.</p> </sec> <sec id="brb3226-sec-0005" sec-type="section"> <title>Discussion and conclusions</title> <p> <italic>CACNA1C</italic> may be associated with biological systems altered in mood disorder. Increases in fronto‐limbic volumes and cognitive ability associated with <italic>CACNA1C</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‐imaging‐cognition‐symptom relationships.</p> </sec> </abstract>