title: Genetic variation in the calcium/calmodulin-dependent protein kinase (CaMK) pathway is associated with antidepressant response in females.
abstract: OBJECTIVE
  Antidepressant effects on monoamine neurotransmission may be influenced by genetic variation in intracellular signal transduction pathways, such as the cyclic adenosine monophosphate (cAMP)--protein kinase A (PKA) pathway, Ras-mitogen activated protein kinase (MAPK) pathway and calcium/calmodulin-dependent protein kinase (CaMK) pathway. The aims of this study were to examine the association of polymorphisms in candidate genes of these three signal transduction pathways with response to antidepressant treatment, and to determine the effects of, and interactions with, environment factors.
  
  
  METHODS
  We recruited 412 patients who met diagnosis criteria for major depressive disorder (MDD) (DSM-IV Axis I). 284 patients completed 8 weeks treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenergic reuptake inhibitors (SNRIs). Severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 8 weeks antidepressant treatment. 209 patients completed the Childhood Trauma Questionnaire, 28 item Short Form (CTQ-SF) which was used to evaluate childhood adverse events. 218 patients completed the Life Events Scale (LES) which were used to evaluate life stress before onset. 155 SNPs in 66 candidate genes were genotyping by Illumina GoldenGate, including 28 SNPs in 15 genes of cAMP-PKA pathway, 37 SNPs in 17 genes of Ras-MAPK pathway and 90 SNPs in 34 genes of CaMK pathway. The remission criterion was HDRS score equal to or less than 7. Single SNP and haplotype associations were analyzed by UNPHASED 3.3.13. Gene-environment interactions were analyzed by binary logistic regression with SPSS 11.0 software.
  
  
  RESULTS
  The rs2230372 SNP in ITPR2, rs2280272 in PRKCZ, rs17109671, and rs17109674 in PLCE1 were significant associated with remission, as were haplotypes in PRKCZ and PLCE1. All these positive associations were found in genes of the CaMK pathway, but not the cAMP-PKA or Ras-MAPK pathways. There were no significant differences in CTQ scores and LES scores between remitters and non-remitters. No significantly interactions between candidate genes and environment effects were observed.
  
  
  CONCLUSIONS
  The CaMK pathway may be important in determining antidepressant response. But recent adverse life events, childhood adversity, and interactions between candidate genes and environment factors appear not to influence short term antidepressant outcome.
authors: Department of Neurology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China.
authors: Yanyan
authors: Y
authors: Shi
authors: Yonggui
authors: Y
authors: Yuan
authors: Zhi
authors: Z
authors: Xu
authors: Mengjia
authors: M
authors: Pu
authors: Congjie
authors: C
authors: Wang
authors: Yumei
authors: Y
authors: Zhang
authors: Zhening
authors: Z
authors: Liu
authors: Chuanyue
authors: C
authors: Wang
authors: Lingjiang
authors: L
authors: Li
authors: Zhijun
authors: Z
authors: Zhang
mesh_terms: D000328:Adult; D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases