Serotonergic and BDNF genes and risk of depression after stroke.
BACKGROUND
Polymorphisms of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) have been investigated as candidate genes for post-stroke depression (PSD). Serotonin 2a receptor (5-HTR2a) genes have not been yet investigated in PSD. This study aimed to investigate whether the 5-HTT, 5-HTR2a, and BDNF genes are associated with PSD independently and/or interactively in a Korean sample with high prevalence of risk alleles.


METHODS
In 276 stroke cases, depression was diagnosed using DSM-IV at 2 weeks after stroke, further classified to major PSD (N=29), all (major plus minor) PSD (N=77), and control (N=199) groups. Associations between PSD and 5-HTTLPR, STin2 VNTR, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF val66met genotypes were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method.


RESULTS
5-HTR2a 1438 A/A genotype was associated with major PSD, while 5-HTTLPR s/s and BDNF met/met genotypes were associated with all PSD. There was a significant interaction between 5-HTR2a 1438A/G and BDNF val66met polymorphisms for major PSD and a borderline significant interaction between 5-HTTLPR and BDNF val66met polymorphisms for all PSD.


CONCLUSIONS
In a large cohort, we found evidence for serotonin and BDNF polymorphisms as susceptibility factors and gene-gene interactions between these systems for depression at 2 weeks post-stroke.
Department of Psychiatry, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea. jmkim@chonnam.ac.kr
Jae-Min
JM
Kim
Robert
R
Stewart
Kyung-Yeol
KY
Bae
Sung-Wan
SW
Kim
Hee-Ju
HJ
Kang
Il-Seon
IS
Shin
Joon-Tae
JT
Kim
Man-Seok
MS
Park
Myung-Kyu
MK
Kim
Sung-Woo
SW
Park
Young-Hoon
YH
Kim
Jong-Keun
JK
Kim
Ki-Hyun
KH
Cho
Jin-Sang
JS
Yoon
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003866:Depressive Disorder / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D020521:Stroke / Q000150:complications / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins