Serotonin transporter polymorphism and long-term effect of antidepressant treatment

Serotonin transporter polymorphism and long-term effect of antidepressant treatment

P.1. Affectiue disorders and antidepressants diagnoses of pediatric bipolar disorder. The goal of this study was to conduct a meta analysis of these s...

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P.1. Affectiue disorders and antidepressants diagnoses of pediatric bipolar disorder. The goal of this study was to conduct a meta analysis of these studies to assess the degree of agreement over the features and correlates of pediatric bipolar disorder. Methods: The literature was searched and all studies identified that collected data from the CBCL in samples of children with bipolar disorder were included in this analysis. The CBCL records, in standardized format, the behavioral problems and competencies of children aged 4 to 18, as reported by their parents or parentsurrogates. The CBCL produces two factors: a) Internalizing, composed of subscales Anxious/Depressed, Withdrawn, Somatic Complaints; and b) Externalizing, consisting of subscales Aggressive and Delinquent in addition to Attention and Social Problems. Random effects models were used to calculate a combined estimate of each of these clinical subscales in bipolar samples. Random effects models in meta-analyses estimate the between study variance and test for heterogeneity in effect sizes across all studies. The Q statistic was used to determine if there was significant heterogeneity between the effect sizes of each study. Results: Publications from four research institutions were found in the extant literature with three cites in the United States (Boston, St. Louis, and Long Island New York) and one site in Newcastle Australia. In each study subjects were administered both structured diagnostic interviews and the CBCL. However, no two groups used the same structured diagnostic interview and each interview was selected because it putatively addressed different components of bipolar illness in children. For none of the subscales, of the CBCL was there any evidence heterogeneity or publication bias (all p-values >0.05). The combined estimates of the Anxiety/depression (69±3.0), Social Problems (69.9±3.5), Attention Problems (72.8± 4.2), Delinquency (69.2±2.8) and Aggression (77.6±4.8) subscales of the CBCL were elevated to within a clinical range. Each of the scales, with the exception of the Attention Problems scales, were found to be significantly greater than subjects with ADHD, bit not bipolar disorder. Conclusion: Despite controversy over the definition and assessment of pediatric bipolar disorder, there was considerable agreement between research sites when standardized parent questionnaires are used. Considering the different focus and method of interview in each of the contributing studies, it is remarkable that heterogeneity was found in none of the estimates from this analysis. Furthermore, the consensus estimates from these studies corroborates previous research indicating the bipolar children are highly aggressive, mixed with depression, and comorbid with ADHD. These findings could be used to foster communication in research and clinical settings and provide a framework to be followed in design a screening instrument for bipolar disorder in children.

Serotonin transporter polymorphism and long-term effect of antidepressant treatment

M.S. Lee, H.Y. Lee. Korea University Hospital, Department of Psychiatry, Seoul, Republic of Korea

Background: Since serotonin neurotrasnmission has an important role on the pathophysiology of depression, the drug that acts on serotonin transporter is a effective antidepressant. The aim of this study is to investigate the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment.


Method: The 175 depressive patients, who met DSM-IV criteria for Major depressive disorder or Dysthymic disorder were enrolled into 3rd year study. The genotypes of the patients were investigated by Polymerase chain reaction of genomic DNA with promoter regions of the serotonin transporter gene. Clinical Global impression was checked six times, at the 1st visit and 8th week, 16th week, 1st year, 2nd, 3rd year after the antidepressant treatment. Result: The genotypes of 138 patients were investigated and 127 of them finished this 1 year study and 107, 97 of them finished this 2, 3 year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(1/l) of long variant showed a better antidepressant therapeutic response than heterozygote(l/s). The heterozygote(l/s) showed a better response than the subset with homozygote(s/s) of short variant at 1st, 2nd and 3rd year after the antidepressant treatment in CGI-global improvement score. Conclusion: This result shows that the serotonin transporter polymorphism may be related to the long-term effect of antidepressant treatment and there may be also ethnic difference.

~ T h e impact of G-2694A and C734A polymorphism of CYPIA2 on the metabolism of clomipramine in Japanese depressive patients G. Hirokane, M. Ueda, S. Morita, A. Yokono, M. Okawa, K. Shimoda. Shiga University of Medical Science, Department of

Psychiatry, Otsu, Japan Recently, it has been reported that G-2694A and C734A polymorphisms of CYP1A2 are related to high inducibility/activity of CYP1A2 assessed by the caffeine metabolic ratio in non smokers as well as smokersl). In this study, we investigated the impact of these two polymorphisms of CYP1A2 on the metabolism of clomipramine (C) in Japanese depressive patients. Forty-eight unrelated patients (18 men and 30 women) receiving C hydrochloride orally participated in this study. Written informed consent was obtained from each subject after the experimental procedure was fully explained. Seven men and two women were regular smokers. The ages of our subjects ranged from 17 to 73 years (mean±SD, 47.64-14.2 years). They were administered 10 to 250 mg/day (91.2+48.7 mg/day) or 0.14 to 4.82 mg/kg body weight (1.76-t-1.02 mg/kg body weight) of C and maintained at the same daily dosage for at least two weeks to obtain the steady-state concentrations. Plasma levels of C and its metabolites N-desmethyl clomipramine (DC) were determined by highperformance liquid chromatography. A point mutation from C to A in intron 1 at position 734 and a point mutation from G to A at position -2964 in the 5'-flanking region of CYP1A2 were identified by polymerase chain reaction-restricted fragment length polymorphism method2,3). The Ethics Committee of Shiga University of Medical Science Hospital approved this study. The allele frequencies of A at -2964 and A at 734 in our subjects were 0.27 and 0.61, respectively. The plasma concentrations of C was 75.6±39.2 ng/ml/(mg/kg body weight) in the G/G at -2964 A/A at 734 genotype (n=5), 56.8±14.5 ng/ml/(mg/kg body weight) in the G/A at -2964 A/A at 734 genotype (n=l 1), 67.9+63.48 ng/ml/(mg/kg body weight) in the A/A at -2964 A/A at 734 genotype (n=3), 108.4-4-83.7 ng/ml/(mg/kg body weight) in the G/G at -2964 A/C at 734 genotype (n=12), 56.4-4-31.0 ng/ml/(mg/kg body weight) in the G/A at -2964 A/C at 734