title: The effects of the CACNA1C rs1006737 A/G on affective startle modulation in healthy males.
abstract: BACKGROUND
  The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation.
  
  
  METHODS
  Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category. Baseline startle was assessed during blank screens. State mood was self-rated on arrival, pre- and post-test and the emotional valence and arousal of affective pictures at post-test.
  
  
  RESULTS
  Relative to the other genotypes, risk A allele homozygotes presented with higher anxiety/negative affect at pre-test, reduced and exaggerated physiological responses to the pleasant and negative pictures respectively, negative affect with reduced arousal at post-test and rated the affective pictures as less arousing and inconsistently to their physiological responses (all P<0.05). Sustained contextual negative mood predicted reduced baseline and affective startle reactivity in the AA group.
  
  
  CONCLUSIONS
  Healthy homozygous males for the risk A allele appear to have marked contextual sensitivity, affective reactivity akin to anxiety and depression and inefficient emotional appraisal. Our findings provide phenotypic detail of the CACNA1C AA genotype in non-symptomatic individuals, which suggest primary effects in emotional circuitry, consistent with previously documented alterations in hippocampal/amygdala processing.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Pasparakis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Koiliari
authors.affiliation: Department of Psychology, University of Crete, Rethymno, Crete, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Zouraraki
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; Aghios Charalambos Mental Health Clinic, Heraklion, Crete, Greece.
authors.forename: E-M
authors.initials: EM
authors.lastname: Tsapakis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece; Department of Psychiatry, Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; James J. Peters VA Medical Center, Mental Illness Research Education and Clinical Center (MIRECC), 130, West Kingsbridge Road, Bronx, NY 10468, USA.
authors.forename: P
authors.initials: P
authors.lastname: Roussos
authors.affiliation: Department of Psychology, University of Crete, Rethymno, Crete, Greece.
authors.forename: S G
authors.initials: SG
authors.lastname: Giakoumaki
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. Electronic address: pbitsios@med.uoc.gr.
authors.forename: P
authors.initials: P
authors.lastname: Bitsios
mesh_terms: D000328:Adult; D000483:Alleles; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000235:genetics*; D009483:Neuropsychological Tests; D010551:Personality / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type
keywords: Bipolar affective disorder; Emotional processing; Genetics; IAPS pictures; Psychosis