Serotonergic and BDNF genes associated with depression 1 week and 1 year after mastectomy for breast cancer.
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.
Department of Psychiatry, Chonnam National University Medical School, 5 Hak-dong, Dong-gu, Gwangju 501-746, Republic of Korea. jmkim@chonnam.ac.kr
Jae-Min
JM
Kim
Sung-Wan
SW
Kim
Robert
R
Stewart
Seon-Young
SY
Kim
Il-Seon
IS
Shin
Min-Ho
MH
Park
Jung-Han
JH
Yoon
Ji-Shin
JS
Lee
Sung-Woo
SW
Park
Young-Hoon
YH
Kim
Jin-Sang
JS
Yoon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000523:psychology / Q000601:surgery*; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015994:Incidence; D007406:Interview, Psychological; D007438:Introns; D016015:Logistic Models; D008408:Mastectomy / Q000009:adverse effects* / Q000523:psychology; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020080:Tandem Repeat Sequences; D013997:Time Factors; D014633:Valine / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008715:Methionine; D014633:Valine