title: Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer.
abstract: BACKGROUND
  Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms.
  
  
  METHODS
  Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions.
  
  
  RESULTS
  There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001).
  
  
  CONCLUSIONS
  The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment.
  
  
  CONCLUSIONS
  BDNF genotype is an indirect measure of BDNF protein levels.
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States. Electronic address: ldooley@psych.ucla.edu.
authors.forename: Larissa N
authors.initials: LN
authors.lastname: Dooley
authors.affiliation: Department of Health Policy & Management, UCLA Fielding School of Public Health, Los Angeles, CA, United States; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, United States.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Cousins Center of Psychoneuroimmunology, Semel Institute for Neuroscience, Los Angeles, CA, United States.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Cole
authors.affiliation: Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, CA, United States.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Crespi
authors.affiliation: Department of Psychology, University of California, Los Angeles, United States; Division of Cancer Prevention and Control Research, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, United States; Cousins Center of Psychoneuroimmunology, Semel Institute for Neuroscience, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
authors.forename: Julienne E
authors.initials: JE
authors.lastname: Bower
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000523:psychology; D002097:C-Reactive Protein / Q000032:analysis; D003863:Depression / Q000097:blood / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000523:psychology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D002097:C-Reactive Protein
keywords: BDNF; Beck Depression inventory-II; Breast cancer; CRP; Depression; Inflammation