***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: The serotonergic neurotransmitter system has been implicated in the pathogenesis of major depressive disorder ( MDD ) . Of the 14 human serotonin ( 5-HT ) receptors , the 5-HT6 receptor may be a c and i date for the study of MDD because of its relative abundance in certain limbic areas and its high affinity to several antidepressants . The present study tested the hypothesis that a 5-HT6 genetic polymorphism ( C267 T ) is associated with the clinical manifestations of , and /or antidepressant response in , MDD . The  Hamilton Depression Rating Scale  was used to assess 57 MDD patients before antidepressant treatment , with 34 patients completing the 4-week treatment and evaluation . The results of the association study provide that the 5-HT6 C267 T genetic variant does not play a major role in producing the clinical manifestations or antidepressant response for MDD patients . Further study with a functional 5-HT6 polymorphism is needed to explore the role of 5-HT6 in the pathogenesis of MDD Prediction of the response to different classes of antidepressants has been an important matter of concern in the field of psychopharmacology . The purpose of the present study was to investigate whether the G196A polymorphism of the brain-derived neurotrophic factor ( BDNF ) gene is associated with the antidepressant effect of milnacipran , a serotonin norepinephrine reuptake inhibitor , and fluvoxamine , a selective serotonin reuptake inhibitor .  The subjects of our previous study of milnacipran ( n = 80 ) and fluvoxamine ( n = 54 ) were included in the present study . Severity of depression was assessed with the Montgomery Åsberg depression rating scale ( MADRS ) . Assessment s were carried out at baseline and at 1 , 2 , 4 and 6 weeks of treatment . Polymerase chain reaction was used to determine allelic variants . In all subjects receiving milnacipran or fluvoxamine , the G/A genotype of the BDNF G196A polymorphism was associated with a significantly better therapeutic effect in the MADRS scores during this study . When milnacipran and fluvoxamine-treated subjects were analysed independently , the G/A genotype group showed greater reduction of MADRS scores than other genotype groups , irrespective of which antidepressant was administered . These results suggest that the BDNF G196A polymorphism in part determines the antidepressant effect of both milnacipran and fluvoxamine 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 Background : Variability in antidepressant response is due to genetic and environmental factors . Since SSRIs exert their activity enhancing the serotonin turnover , genes coding for proteins of the serotonin system are key c and i date s for a possible genetic influence with response to SSRIs . Therefore tryptophan hydroxylase ( TPH ) , the rate-limiting enzyme in the bio synthesis of serotonin in the raphe nuclei could be a c and i date . In the present study , we examined the possible association of the TPH1 218A/C polymorphism with response to SSRIs in a sample of Japanese patients with major depression . Methods : The  21-item Hamilton Rating Scale for Depression ( HAM-D ) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment . All patients were genotyped for the TPH1 218A/C polymorphism . Results : Repeated- measures analysis of variance of HAM-D score change over time with baseline scores and 5-HTTLPR variants included in the model as covariate showed no significant association of this SNP with treatment response to SSRIs . Furthermore , no significant association of this SNP could be observed with both responder rate at weeks 2 , 4 and 6 and intolerance to SSRIs . Conclusion : The result suggests that 218A/C variants of TPH1 can not play a major role as predictor of treatment response as well as intolerance in Japanese patients with major depression The clinical efficacy of a systemically administered drug acting on the central nervous system depends on its ability to pass the blood-brain barrier , which is regulated by transporter molecules such as ABCB1 ( MDR1 ) . Here we report that polymorphisms in the ABCB1 gene predict the response to antidepressant treatment  in those depressed patients receiving drugs that have been identified as substrates of ABCB1 using abcb1ab double-knockout mice . Our results indicate that the combined consideration of both the medication 's capacity to act as an ABCB1-transporter substrate and the patient 's ABCB1 genotype are strong predictors for achieving a remission . This finding can be viewed as a further step into personalized antidepressant treatment In the context of a long term follow-up study , we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram .  The sample consisted of 131 patients , all of Spanish origin , diagnosed according to DSM-IV criteria .  A 21-item Hamilton Depression Rating Scale ( HDRS ) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week , respectively . Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week ( χ2 = 8.7 , P = 0.013 ) . Moreover , homozygous for the allele S presented three times more risk for non reaching remission of depressive episode  after citalopram treatment than patients with any other 5-HTTLPR genotype combination ( χ2 : 7.29 , P = 0.006 ; OR = 3.23 [ 95%CI : 1.24–8.5 ] ) . In conclusion , our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment 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 The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action Several studies have demonstrated the involvement of 5-HT1A receptors in the pathogenesis of depression and in the antidepressant response to SSRIs . A functional new variant in the promoter region of the 5-HT1A gene was recently reported ( -1019 C > G ) . The aim of this study is to investigate a possible association between this 5-HT1A receptor variant and antidepressant response to fluvoxamine in a sample of 262 mood-disorder subjects ( 151 major depressed and 111 bipolars ) treated with fluvoxamine for 6 wk . The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression ( HAMD ) . 5-HT1A variants did not influence antidepressant response in the whole sample and in unipolar subjects . In bipolars , 5-HT1A*C/C genotype carriers showed a better response to fluvoxamine  ( p=0.036 ) , independently from clinical variables . The 5-HT1A polymorphism effect on antidepressant response was independent from the previously reported effect of the 5-HTTLPR polymorphism . In conclusion , 5-HT1A variants could influence the antidepressant efficacy in bipolar subjects , even if results must be verified on larger sample The occurrence of sexual side-effects from antidepressants is thought to be mediated through serotonin 2A ( 5HT2A ) receptors . It is currently 
    Output:
    
Although some heterogeneity was present across studies , our finding suggests that 5-HTTLPR , STin2 , HTR1A , HTR2A , TPH1 and BDNF may modulate antidepressant response