title: The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males.
abstract: OBJECTIVE
  The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression. The aim of this study was to examine the phenotypic consequences of the risk CACNA1C and ANK3 alleles in a large homogeneous cohort of healthy young males.
  
  
  METHODS
  We recruited 703 randomly selected, healthy army conscripts (mean age 22.1 ± 3.0 years) from the first wave of the Learning on Genetics of Schizophrenia project in Heraklion, Crete. Of those recruited, 530 subjects entered and completed the study. Subjects were assessed for prepulse inhibition (PPI), startle reactivity, neuropsychology, and personality.
  
  
  RESULTS
  UNPHASED analysis revealed that the rs1006737 A-allele was associated with lower extraversion and higher harm avoidance, trait anxiety, and paranoid ideation, while the rs10994336 T-allele was associated with lower novelty seeking and behavioral activation scores (p < 0.01). Both alleles were associated with high startle reactivity (p < 0.05). There were no significant associations with any cognitive task performance or PPI.
  
  
  CONCLUSIONS
  The CACNA1C genotype was associated with proneness to anxiety and negative mood, while the ANK3 genotype was associated with proneness to anhedonia. Both risk genotypes were associated with high startle reactivity, suggesting a role of these polymorphisms in threat/stress signal processing, probably in the hippocampus and/or amygdala. None of the risk genotypes affected sensorimotor gating or behavioral performance in an extensive battery of executive function tests in this cohort of healthy males.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Crete, Heraklion, Greece. pbitsios@med.uoc.gr
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos
authors.forename: Stella G
authors.initials: SG
authors.lastname: Giakoumaki
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgakopoulos
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Robakis
authors.forename: Panos
authors.initials: P
authors.lastname: Bitsios
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D017487:Ankyrins / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece; D006801:Humans; D008297:Male; D008889:Military Personnel; D019964:Mood Disorders / Q000235:genetics*; D009483:Neuropsychological Tests; D010551:Personality / Q000235:genetics*; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics; D012307:Risk Factors; D055139:Sensory Gating / Q000235:genetics; D055815:Young Adult
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type