Does 5HTTLPR long allele prevent hospitalization? Test of Hardy-Weinberg equilibrium
ABSTRACT Many studies suggest an association of the serotonin transporter gene polymorphism (5HTTLPR) long allele with better antidepressant treatment response than the short allele. However, there is controversy over these findings. We hypothesized that if the long allele is associated with a better outcome, we would find fewer inpatients with the long allele compared with the short allele. Chart review identified 925 depressed inpatients and 201 outpatients genotyped for 5HTTLPR. The sample was primarily White (>90%). We tested potential departures from Hardy-Weinberg equilibrium for each sample. We analyzed three independent sets of inpatient samples separately and combined, a White subgroup of 791 patients of the total 925 inpatients, and 201 outpatients. There was no departure from Hardy-Weinberg equilibrium with any of these samples. We also compared 5HTTLPR genotype prevalence between 925 inpatients and 201 outpatients, which showed no statistically significant difference.
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ABSTRACT: The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been proposed as a predictor of antidepressant response. Insertion or deletion of a 44-base pair-long region gives rise to short "S" and long "L" forms of the promoter region, the "S" form being associated with reduced serotonin transporter expression. A systematic review and meta-analysis was performed to clarify the effect of 5-HTTLPR on antidepressant response and remission rates. Data were obtained from 28 studies with 5408 participants. Three genotype comparisons were tested-SS versus (SL or LL), (SS or SL) versus LL, and SS versus LL. There was no statistically significant effect on antidepressant response. Compared with L carriers, there was an apparent effect of the SS genotype on remission rate (relative risk: .88; 95% confidence interval: .79-.98; p = .02). However, after trim and fill correction for missing data, the effect disappeared (relative risk: .92; 95% confidence interval: .81-1.05; p = .23), indicating that the initial significant effect was likely the result of publication bias. No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL. Substantial unexplained heterogeneity of effect sizes was observed between studies, pointing to additional interacting factors contributing to an association in some cases. The 5-HTTLPR biallelic short/long polymorphism by itself does not seem to usefully predict antidepressant response.Biological psychiatry 09/2010; 68(6):536-43. DOI:10.1016/j.biopsych.2010.04.034 · 9.47 Impact Factor
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ABSTRACT: The short form of the indel promoter polymorphism (5HTTLPR) of the serotonin transporter gene (SLC6A4) and a history of child abuse have been reported to be associated with an increased risk for the development of depression. A child abuse history has also been associated with more rapid heart rate reactions. A retrospective chart review identified 282 patients with major depression who had been hospitalized and genotyped for the 5HTTLPR polymorphism. A subgroup of 185 females of European ancestry was also identified and analyzed. While hospitalized, heart rate was measured. Child abuse history was documented during the diagnostic evaluation. Analyses of the relationship between 5HTTLPR genotype, history of child abuse, and admission heart rate were conducted. No main effect on heart rate from the 5HTTLPR genotype or a child abuse history was demonstrated for the entire sample or the subgroup of female patients. However, a genotype-by-abuse interaction was associated with resting heart rate on admission to the hospital (P<.05). Depressed patients, who were homozygous for the long allele and who had been abused, had a heart rate on hospital admission, which was statistically higher than patients with the same genotype but who had not been abused. These findings were consistent both for the 282 patients (7.2 bpm higher) as well as for the subgroup of 185 female patients of European ancestry (9.6 bpm higher). CONCLUSIONs: A 5HTTLPR genotype interaction of elevated heart rate with a history of child abuse was demonstrated in depressed psychiatric inpatients.Depression and Anxiety 03/2011; 28(3):227-33. DOI:10.1002/da.20779 · 4.29 Impact Factor
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ABSTRACT: The author explored depression management outcomes in an outpatient psychosomatic medicine (PM) practice to identify factors associated with treatment response. Medical records of 251 patients seen in the Mayo Clinic Rochester outpatient PM clinic who had patient health questionnaire-9 (PHQ-9) scores at the time of initial consultation and after consultation were reviewed. Comparisons of differences in pre- and post-consultation PHQ-9 scores were evaluated to identify patients with treatment response (score decreased > 50%). A total of 112 (44.6%) patients had initial PHQ-9 scores ≥ 5. Univariate comparisons revealed higher likelihood of response (25.9%) with lower average number of past antidepressant and antipsychotic trials, and reported good friend and family social support. After controlling for average number of medication trials, reported good friend support remained predictive of response (OR 3.4225, χ2 4.6743, P = 0.31); there was a trend for reported good family support to remain predictive (OR 2.7956; χ2 2.5933, P= 0.097). Though exploratory and underpowered to adequately assess all potential contributors, retrospective examination of factors associated with depression treatment-response in this outpatient PM practice emphasizes the relevance of perception of social support as markers of prognosis and outcome.Psychosomatics 02/2012; 53(4):387-91. DOI:10.1016/j.psym.2011.04.004 · 1.67 Impact Factor