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 CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptConclusion-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. KeywordsTraumatic brain injury; serotonin receptors; serotonin transporter; brain derived neurotrophic factor (BDNF); methylenetetrahydrofolate reductase (MTHFR); tryptophan hydroxylase (TPH)

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.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti-depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of < or =7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.