Genetic predictors of response to treatment with citalopram in depression secondary to traumatic brain injury.

OBJECTIVES: 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). CONCLUSION: 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.

A randomized controlled trial of antidepressant continuation for major depression following traumatic brain injury.

OBJECTIVE: This study examines whether continuation therapy with citalopram can prevent a relapse following remission of major depression due to traumatic brain injury. METHOD: After 65 subjects with DSM-IV-diagnosed major depression following traumatic brain injury were treated with open-label citalopram (20 mg to 50 mg/d), 25 subjects (38.5%) met criteria for remission. Of those, 21 (84.0%) were randomly assigned to either same-dose citalopram or placebo and followed monthly over 40 weeks. Remission was defined as a Hamilton Depression Rating Scale (HDRS) score of ≤ 7 or a Clinical Global Impressions-Improvement rating of "much improved" or better. The main outcome variable was the presence of relapse, as defined by meeting criteria for major depressive episode according to the DSM-IV and an HDRS score ≥ 16. Data were collected from February 16, 2005, to May 5, 2008. RESULTS: Ten subjects were randomly assigned to citalopram and 11 to placebo. There were 3 dropouts, including 1 for adverse drug effects (diarrhea). Relapse occurred in 11 subjects (52.4%), with a mean ± SD time to relapse of 23.52 ± 16.6 weeks. The groups did not differ in relapse rates (drug: 50.0% [5/10] vs placebo: 54.5% [6/11], Fisher exact test, P = .835) or time to relapse (log rank test χ² = 0.148, P = .700). CONCLUSIONS: The present study suggests important limitations of continuation pharmacotherapy in the prevention of relapse of major depression following traumatic brain injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00162916.

Factor analysis of the Rivermead Post-Concussion Symptoms Questionnaire in mild-to-moderate traumatic brain injury patients.

Posttraumatic brain injury patients with depressive symptoms were compared with nondepressed mild and moderate traumatic brain injury (TBI) patients based on their scores on the Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ). A factor analysis demonstrated that the items of the RPCSQ loaded into three factors: mood and cognition, general somatic, and visual somatic symptom groups. Factor scores based on this model were calculated for each group and it was found that depressed subjects reported a greater severity of all three symptom groups compared to nondepressed patients. These results suggest that depression post-TBI may influence patient perception of postconcussion symptoms.

The serotonin transporter polymorphisms and major depression following traumatic brain injury.

OBJECTIVE: The purpose of this study was to examine the role of the serotonin transporter gene polymorphisms on the risk of major depression following traumatic brain injury (TBI). METHODS: Seventy-five patients who had sustained a TBI and who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for mood disorder due to TBI were compared to 99 controls with TBI but no mood disorder. The severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) for the depressed patients. All patients were genotyped for the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with the assay for the rs25531 allelic variant. RESULTS: The distribution of genotype frequencies was not different between the depressed and control groups (chi(2) = 1.43, df = 2, p = 0.488) and for the depressed patients there was no association between HAMD scores and the polymorphisms (t-test = 1.71, df = 68, p = 0.092). CONCLUSION: There was no evidence of association between the serotonin transporter gene polymorphisms and depression post-TBI. Future research is indicated into the possible role of other candidate genes as risk factors for depression in this population.