Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury.
OBJECTIVE
To determine which serotonergic system-related single nucleotide polymorphisms (SNPs) predicted variation in treatment response to citalopram in depression following a traumatic brain injury (TBI).


METHODS
Ninety (50 M/40 F, aged 39.9, SD = 18.0 years) post-TBI patients with a major depressive episode (MDE) were recruited into a 6-week open-label study of citalopram (20 mg/day). Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025).


RESULTS
MTHFR and BDNF SNPs predicted greater treatment response (R(2)= 0.098, F = 4.65, p = 0.013). The 5HTTLPR predicted greater occurrence of adverse events (R(2)= 0.069, F = 5.72, p = 0.020).


CONCLUSIONS
Results suggest that polymorphisms in genes related to the serotonergic system may help predict short-term response to citalopram and tolerability to the medication in patients with MDE following a TBI.
Lanctôt
Krista L
KL
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. krista.lanctot@sunnybrook.ca
Rapoport
Mark J
MJ
Chan
Florance
F
Rajaram
Ryan D
RD
Strauss
John
J
Sicard
Tricia
T
McCullagh
Scott
S
Feinstein
Anthony
A
Kiss
Alex
A
Kennedy
James L
JL
Bassett
Anne S
AS
Herrmann
Nathan
N
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000235:genetics*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000187:drug effects / Q000235:genetics
D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)