***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background As compared with the long variant ( L ) , the short variant ( S ) of the functional polymorphic region of the serotonin transporter gene ( 5-HTTLPR ) has been associated with a lower antidepressant efficacy in major depression , but some replication studies have evidence d contradictory results . Sex differences may explain these contradictory results . Methods One hundred and three in patients ( 74 women and 29 men ) with a major depressive episode were assessed prospect ively for antidepressant efficacy after 4 weeks of treatment with selective serotonin reuptake inhibitors ( SSRI ) and non-SSRI drugs . Results As compared with LL/LS , the SS genotype of the 5-HTTLPR was associated with a lower antidepressant efficacy in depressed women ( 79 vs. 50 % responders , P = 0.035 ) . This result was shown with both SSRI and non-SSRI antidepressants . The logistic regression performed in women showed that response to treatment was related to genotype ( odds ratio=0.15 ; 95 % confidence interval=0.03–0.85 ; P = 0.03 ) and not to other variables . No effect of 5-HTTLPR was found in depressed men . Conclusion Despite a low power , this study suggests a significant effect of 5-HTTLPR genotype on antidepressant efficacy in depressed women but not in men , with both SSRI and non-SSRI drugs . Further research is needed to confirm this result and investigate its underlying mechanisms Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors ( SSRIs ) . The serotonin transporter ( 5-HTT ) is a prime target for SSRIs . A functional polymorphism within the promoter region of the 5-HTT gene , leading to different transcriptional efficiency , was recently reported . We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and /or augmentation with pindolol ( a serotonin autoreceptors antagonist ) which has been suggested as an augmentation therapy for nonresponders . One hundred and two in patients with major depression with psychotic features were r and omly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks . Depression severity was assessed once a week using the Hamilton Depression Rating Scale . Allelic variation in each subject was determined using a PCR-based method . Data were analyzed with a three-way repeated measures analysis of variance . Both homozygotes for the long variant ( l/l ) of the 5-HTT promoter and heterozygotes ( l/s ) showed a better response to fluvoxamine than homozygotes for the short variant ( s/s ) . In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone .  Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene . Even though other factors may be implicated , genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression Genome-wide association studies ( GWASs ) have identified several susceptibility loci for bipolar disorder ( BD ) and shown that the genetic architecture of BD can be explained by polygenicity , with numerous variants contributing to BD . In the present GWAS ( Phase I/II ) , which included 2964 BD and 61 887 control subjects from the Japanese population , we detected a novel susceptibility locus at 11q12.2 ( rs28456 , P=6.4 × 10−9 ) , a region known to contain regulatory genes for plasma lipid levels ( FADS1/2/3 ) . A subsequent meta- analysis of Phase I/II and the Psychiatric GWAS Consortium for BD ( PGC-BD ) identified another novel BD gene , NFIX ( Pbest=5.8 × 10−10 ) , and supported three regions previously implicated in BD susceptibility : MAD1L1 ( Pbest=1.9 × 10−9 ) , TRANK1 ( Pbest=2.1 × 10−9 ) and ODZ4 ( Pbest=3.3 × 10−9 ) . Polygenicity of BD within Japanese and trans-European-Japanese population s was assessed with risk profile score analysis . We detected higher scores in BD cases both within ( Phase I/II ) and across population s ( Phase I/II and PGC-BD ) . These were defined by ( 1 ) Phase II as discovery and Phase I as target , or vice versa ( for ‘ within Japanese comparisons ’ , Pbest~10−29 , R2~2 % ) , and ( 2 ) European PGC-BD as discovery and Japanese BD ( Phase I/II ) as target ( for ‘ trans-European-Japanese comparison , ’ Pbest~10−13 , R2~0.27 % ) . This ‘ trans population ’ effect was supported by estimation of the genetic correlation using the effect size based on each population ( liability estimates~0.7 ) . These results indicate that ( 1 ) two novel and three previously implicated loci are significantly associated with BD and that ( 2 ) BD ‘ risk ’ effect are shared between Japanese and European population The aim of the present study was to test a possible effect of the A218C tryptophan hydroxylase ( TPH ) gene variant on the antidepressant activity of fluvoxamine in a sample of major and bipolar depressives , with or without psychotic features . Two hundred and seventeen in patients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double blind design for 6 weeks . The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression . TPH allelic variants were determined in each subject by using a PCR-based technique . No significant finding was observed in the overall sample as well as in the pindolol group , while TPH*A/A was associated with a slower response to fluvoxamine treatment in subjects not taking pindolol ( P = 0.001 ) . This effect was independent from the previously reported influence of 5-HTTLPR polymorphism . If confirmed , these results may shed further light on the genetically determined component of the response to pharmacological treatments , thus helping the clinician to individualize each patient 's therapy according to their genetic pattern We examined allelic polymorphisms of the serotonin transporter ( 5-HTT ) gene and antidepressant response to 6 weeks ' treatment with the selective serotonin reuptake inhibitor ( SSRI ) drugs fluoxetine or paroxetine . We genotyped 120 patients and 252 normal controls , using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene . Diagnosis of depression was not associated with 5-HTT polymorphisms . Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others ( p < 0.0001 , p = 0.0074 , respectively ) . Lack of the I/I allele form in intron 2 most powerfully predicted non-response ( 83.3 % ) . Response to SSRI drugs  is related to allelic variation in the 5-HTT gene in depressed Korean patients BACKGROUND To date almost 200 genes were found to be associated with major depressive disorder ( MDD ) or suicide attempts ( SA ) , but very few genes were reported for their molecular mechanisms . This study aim ed to find out whether there were common or rare variants in three c and i date genes altering the risk for MDD and SA in Chinese . METHODS Three c and i date genes ( HOMER1 , SLC6A4 and TEF ) were chosen for resequencing analysis and association studies as they were reported to be involved in the etiology of MDD and SA . Following that , bioinformatics analyses were applied on those variants of interest . RESULTS After resequencing analysis and alignment for the amplicons , a total of 34 common or rare variants were found in the r and omly selected 36 Hong Kong Chinese patients with both MDD and SA . Among those , seven variants show potentially deleterious features . Rs60029191 and a rare variant located in regulatory region of the HOMER1 gene may affect the promoter activities through interacting with predicted transcription factors . Two missense mutations existed in the SLC6A4 coding regions were firstly reported in Hong Kong Chinese MDD and SA patients , and both of them could affect the transport efficiency of SLC6A4 to serotonin . Moreover , a common variant rs6354 located in the untranslated region of this gene may affect the expression level or exonic splicing of serotonin transporter . In addition , both of a most studied polymorphism rs738499 and a low-frequency variant in the promoter region of the TEF gene were found to be located in potential transcription factor binding sites , which may let the two variants be able to influence the promoter activities of the gene . CONCLUSIONS This study eluci date d the potentially molecular mechanisms of the three c and i date genes altering the risk for MDD and SA . These findings implied that not only common variants but rare variants could make contributions to the genetic susceptibility to MDD and SA in Chinese Serotonin transporter promoter length polymorphism ( 5-HTTLPR ) has been implicated in the pathogenesis of mood disorders and in the therapeutic response to serotonergic drugs . In this study , the 5-HTTLPR was estimated in 67 patients with bipolar mood disorder , receiving lithium carbonate for prophylactic purpose s for the period of more than 5 years ( mean 15 years ) . The patients were divided into excellent responders ( n = 18 ) , partial responders ( n = 35 ) and poor responders ( n = 14 ) . In lithium non-responders , the genotype s/s and the allele s was significantly more frequent than in excellent and partial responders . The obtained results are discussed in view of other studies showing an association of S genotype with worse response to serotonergic drugs .  A supposition is made that prophylactic management of bipolar illness can be optimized by defining 5-HTTLPR genotype The aim of our study was to investigate gene variants in the long-term outcome of mood disorders . We retrospectively studied a sample of in patients affected by recurrent and rapid cycling mood disorders . The serotonin transporter gene-linked functional polymorphic region ( 5-HTTLPR ) and the A218C tryptophan hydroxylase ( TPH ) gene variant were determined using a PCR-based technique . For 5-HTTLPR polymorphism we genotyped 435 in patients affected by major depressive ( n=153 ) , bipolar ( n=213 ) and rapid cycling ( n=69 ) mood disorders and 456 controls ; for TPH we genotyped 399 in patients ( MD , n=132 ; BP , n=203 ; rapid cycling n=64 ) and 259 controls . R and om Regression Model analysis was used to investigate the longitudinal time course of the illness . 5-HTTLPR and TPH polymorphisms were not associated with mood disorders time course . However we observed an excess of 5-HTTLPR*long alleles among rapid cycling subjects compared to both controls ( P=0.018 ) and remitting mood disorders ( P=0.006 ) . TPH frequencies did not differ between mood disorders subtypes . Our results suggest that 5-HTTLPR variants may confer a susceptibility toward rapid cycling mood disorders Methods of sample size and power calculations are review ed for the most common study design s. The sample size and power equations for these design s are shown to be special cases of two generic formulae for sample size and power calculations . A computer program is available that can be used for studies with dichotomous , continuous , or survival response measures . The alternative hypotheses of interest may be specified either in terms of differing response rates , means , or survival times , or in terms of relative risks or odds ratios . Studies with dichotomous or continuous outcomes may involve either a matched or independent study design . The program can determine the sample size needed to detect a specified alternative hypothesis with the required power , the power with which a specific alternative hypothesis can be detected with a given sample size , or the specific alternative hypotheses that can be detected with a given power and sample size . The program can generate help messages on request that facilitate the use of this software . It writes a log file of all calculated estimates and can produce an output file for plotting power curves . It is written in FORTRAN-77 and is in the public domain BACKGROUND It has been recently reported that the short variant of the serotonin transporter ( 5-HTT ) gene-linked functional polymorphic region ( 5-HTTLPR ) influences the antidepressant response to certain selective serotonin reuptake inhibitors . The aim of the present study was to test this finding in a sample of major and bipolar depressives , with or without psychotic features . METHODS One hundred fifty-five in patients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks . The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression . Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique . RESULTS 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment , independently from the recorded clinical variables . More specifically , the diagnosis , the presence of psychotic features , and the severity of depressive symptomatology did not influence this association . Conversely ,  pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects , thus reducing the difference in the response rate among the genotype variants . CONCLUSIONS If confirmed , these results may improve patient care by helping the clinician to individualize treatment according to the patient 's genetic 5-HTTL 
    Output:
    
Conclusions : The present study supported the presence of a marginal but detectable effect of the 5‐HTTLPR on susceptibility to BPD .
Besides , the 5‐HTTLPR was identified as a useful predictor for anti‐depressive remission but not for anti‐depressive or anti‐manic response .
HIGHLIGHTSThis study not only assessed association of the 5‐HTTLPR with BPD , but also evaluated effect of the 5‐HTTLPR on treatment response .
The 5‐HTTLPR was identified as a useful predictor for anti‐depressive remission ( p=.006 ) but not for anti‐depressive or anti‐manic response