Psychosomatic medicine · 2011
Serotonergic and BDNF genes associated with depression 1 week and 1 year after mastectomy for breast cancer.
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Kim Jae-Min, Kim Sung-Wan, Stewart Robert, Kim Seon-Young, Shin Il-Seon, Park Min-Ho, Yoon Jung-Han, Lee Ji-Shin, Park Sung-Woo, Kim Young-Hoon, Yoon Jin-Sang
Аннотация
OBJECTIVE: Polymorphisms of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) genes have been investigated as candidate genes for depression occurring in medical disorders. The serotonin 2a receptor (5-HTR2a) genes have been investigated as risk factors for depression but rarely in combination with medical conditions. This study aimed to investigate whether polymorphisms of interest in 5-HTT, 5-HTR2a, and BDNF genes are associated with depression after mastectomy for breast cancer.
METHODS: A total of 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 patients (79%) were followed up 1 year later. Depression (major and minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview and was classified into prevalent, persistent, and incident depression. Individual associations with 5-HTT gene-linked promoter region, serotonin transporter intron 2 variable number tandem repeat, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF Val66Met polymorphisms were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method.
RESULTS: At baseline, 74 patients (24%) were classified with prevalent depression, and at follow-up, 19 patients (8%) and 25 patients (10%) were classified with persistent and incident depression, respectively. The BDNF Met/Met genotype was independently associated with prevalent (odds ratio = 2.63, 95% confidence interval = 1.12-6.14) and persistent (odds ratio = 8.07, 95% confidence interval = 1.26-51.6) depression. No associations with 5-HTT and 5-HTR2a genes (all p values > .21) were found, and no significant gene-gene interactions were identified (all p values > .36).
CONCLUSIONS: Our findings support a role of BDNF, not serotonin, in the etiology of depression occurring in women with breast cancer who received a mastectomy.
METHODS: A total of 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 patients (79%) were followed up 1 year later. Depression (major and minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview and was classified into prevalent, persistent, and incident depression. Individual associations with 5-HTT gene-linked promoter region, serotonin transporter intron 2 variable number tandem repeat, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF Val66Met polymorphisms were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method.
RESULTS: At baseline, 74 patients (24%) were classified with prevalent depression, and at follow-up, 19 patients (8%) and 25 patients (10%) were classified with persistent and incident depression, respectively. The BDNF Met/Met genotype was independently associated with prevalent (odds ratio = 2.63, 95% confidence interval = 1.12-6.14) and persistent (odds ratio = 8.07, 95% confidence interval = 1.26-51.6) depression. No associations with 5-HTT and 5-HTR2a genes (all p values > .21) were found, and no significant gene-gene interactions were identified (all p values > .36).
CONCLUSIONS: Our findings support a role of BDNF, not serotonin, in the etiology of depression occurring in women with breast cancer who received a mastectomy.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAllelesAmino Acid SubstitutionBrain-Derived Neurotrophic FactorBreast NeoplasmsDepressive DisorderDiagnostic and Statistical Manual of Mental DisordersEpistasis, GeneticFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansIncidenceInterview, PsychologicalIntronsLogistic ModelsMastectomyMethionineMiddle AgedMultifactor Dimensionality ReductionPolymorphism, GeneticPrevalencePromoter Regions, GeneticRisk FactorsSerotonin Plasma Membrane Transport ProteinsTandem Repeat SequencesTime FactorsValine