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- Title
Candidate gene associations with mood disorder, cognitive vulnerability, and fronto-limbic volumes.
- Authors
Frazier, Thomas W.; Youngstrom, Eric A.; Frankel, Brian A.; Zunta‐Soares, Giovana B.; Sanches, Marsal; Escamilla, Michael; Nielsen, David A.; Soares, Jair C.
- Abstract
Background Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function: ANK3 (rs10994336), BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191). Aims The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto-limbic regions implicated in affect regulation. Methods and materials 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®). 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. Results Carriers of the minor BDNF and ANK3 alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients ( P = 0.047). CACNA1 C minor allele carriers had larger bilateral caudate, insula, globus pallidus, frontal pole, and nucleus accumbens volumes (smallest r = 0.13, P = 0.043), and increased IQ ( r = 0.18, P < 0.001). CACNA1 C 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. Discussion and conclusions CACNA1 C may be associated with biological systems altered in mood disorder. Increases in fronto-limbic volumes and cognitive ability associated with CACNA1 C 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.
- Subjects
AFFECTIVE disorders; MENTAL depression; COGNITIVE ability; COGNITION; GLOBUS pallidus; NEUROPSYCHIATRY
- Publication
Brain & Behavior, 2014, Vol 4, Issue 3, p418
- ISSN
2162-3279
- Publication type
Article
- DOI
10.1002/brb3.226