BACKGROUND: Anger and irritability are prominent in a subset of individuals with major depressive disorder (MDD). Phosphorylation of the transcription factor cyclic adenosine monophosphate (cAMP) Response Element Binding Protein (CREB) has been associated with aggression or reward/aversion in rodents, and markers near CREB1 have been linked to MDD. Therefore, we examined the association between CREB1 polymorphisms and anger expression in MDD. METHODS: A clinical sample of 94 Caucasian outpatients with MDD (42 male, 52 female) completed the Spielberger State-Trait Anger Expression Inventory. We examined six tagging single nucleotide polymorphisms (SNPs) spanning CREB1 and flanking regions for association with a summary measure of frequency and intensity of anger expression. We also introduced a novel statistical method to dissect the independent effect of individual SNPs and haplotypes. RESULTS: For the sample as a whole, one of six SNPs tested was significantly associated with anger expression (empirical p = .003). Among the male subsample, this association was particularly marked (empirical p = 8 x 10(-5)). A global haplotype test of the six SNPs was likewise significant (p = 3.7 x 10(-6)). No single SNP or haplotype accounted for all of the association observed. CONCLUSION: These preliminary results suggest a strong, gender-specific association between variation at the CREB1 locus and anger expression in MDD.
BACKGROUND: Anger and irritability are prominent in a subset of individuals with major depressive disorder (MDD). Phosphorylation of the transcription factor cyclic adenosine monophosphate (cAMP) Response Element Binding Protein (CREB) has been associated with aggression or reward/aversion in rodents, and markers near CREB1 have been linked to MDD. Therefore, we examined the association between CREB1 polymorphisms and anger expression in MDD. METHODS: A clinical sample of 94 Caucasian outpatients with MDD (42 male, 52 female) completed the Spielberger State-Trait Anger Expression Inventory. We examined six tagging single nucleotide polymorphisms (SNPs) spanning CREB1 and flanking regions for association with a summary measure of frequency and intensity of anger expression. We also introduced a novel statistical method to dissect the independent effect of individual SNPs and haplotypes. RESULTS: For the sample as a whole, one of six SNPs tested was significantly associated with anger expression (empirical p = .003). Among the male subsample, this association was particularly marked (empirical p = 8 x 10(-5)). A global haplotype test of the six SNPs was likewise significant (p = 3.7 x 10(-6)). No single SNP or haplotype accounted for all of the association observed. CONCLUSION: These preliminary results suggest a strong, gender-specific association between variation at the CREB1 locus and anger expression in MDD.
Authors: Roy H Perlis; Daphne J Holt; Jordan W Smoller; Anne J Blood; Sang Lee; Byoung Woo Kim; Myung Joo Lee; Mei Sun; Nikos Makris; David K Kennedy; Kathryn Rooney; Darin D Dougherty; Rick Hoge; Jerrold F Rosenbaum; Maurizio Fava; James Gusella; Gregory P Gasic; Hans C Breiter Journal: Arch Gen Psychiatry Date: 2008-08
Authors: Stephanie S Daniel; David B Goldston; Alaattin Erkanli; Joseph C Franklin; Andrew M Mayfield Journal: J Clin Child Adolesc Psychol Date: 2009-09
Authors: Brion S Maher; Hugh B Hughes; Wendy N Zubenko; George S Zubenko Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2010-01-05 Impact factor: 3.568
Authors: George S Zubenko; Michelle L Jones; Annette O Estevez; Hugh B Hughes; Miguel Estevez Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-01-05 Impact factor: 3.568
Authors: X Xiao; C Zhang; M Grigoroiu-Serbanescu; L Wang; L Li; D Zhou; T-F Yuan; C Wang; H Chang; Y Wu; Y Li; D-D Wu; Y-G Yao; M Li Journal: Mol Psychiatry Date: 2017-11-21 Impact factor: 15.992