***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 hypothesis implicating the serotonergic system in the pathophysiology of obsessive-compulsive disorder ( OCD ) is supported by the therapeutic efficacy of selective serotonin reuptake inhibitors ( SSRIs ) . Since SSRIs act on the serotonin transporter ( 5-HTT ) , it has been suggested that the 5-HTT gene ( SCL6A4 ) could be a good c and i date for OCD . The SCL6A4 gene has a 44-bp insertion/deletion polymorphism in its promoter region ( 5-HTTLPR ) . Previous studies have revealed an association between OCD and the l allele . We analysed the  5-HTTLPR polymorphic system  in 115 Mexican OCD patients and 136 controls . No significant association was found between l allele and OCD ( chi2 = 1.54 , d.f . = 1 , p = 0.21 ) . Furthermore , we assessed alternative methods that employ family-based design s in a sample of 43 trios .  Haplotype-based haplotype relative risk and transmission disequilibrium analysis did not show a preferential transmission of l allele to OCD prob and s. Our results indicate the need to analyse larger sample s using family-based methods Results from family studies have suggested that obsessive‐compulsive disorder ( OCD ) is a genetically heterogeneous disorder and have emphasized the importance of identifying valid subgroups of patients . The current study focused on early‐onset OCD prob and s and examined the recurrence risks of OCD and tics among first‐degree family members . One hundred six children and adolescents with OCD were recruited from a specialty clinic for OCD and 44 control individuals without OCD were identified by r and om‐digit dialing . These 150 prob and s and their 465 first‐degree relatives were assessed by trained interviewers , using st and ardized semi‐structured interviews . Diagnoses were assigned according to DSM‐IV criteria by two experts blind to the prob and 's diagnosis , through the best‐estimate process . These data were analyzed using χ2 tests , t‐tests , logistic regression , and generalized estimating equations ( GEE ) . Case prob and s had a mean age of onset of OC symptoms of 6.7 years ( SD = 2.8 ) , and high comorbid rates with Tourette syndrome ( 33 % ) and chronic tics ( 13.2 % ) . Compared to control relatives , case relatives had higher age‐corrected recurrence risks of OCD ( 22.7 % vs. 0.9 % , odds ratio ( OR ) = 32.5 , 95 % confidence interval ( CI ) = 4.5–230.8 , P = 0.0005 ) , and chronic tics ( 11.6 % vs. 1.7 % , OR = 7.9 , 95 % CI = 1.9–33.1 , P = 0.005 ) . A comorbid diagnosis of tics in the relatives was the best predictor of their diagnosis of OCD ( OR = 7.35 , 95 % CI = 3.79–14.25 , P < 0.0001 ) . There was a significant correlation between the ages of onset of OCD in prob and s and their affected relatives . Childhood onset OCD is a highly familial disorder . Some early‐onset cases may represent a valid subgroup , with higher genetic loading and shared vulnerability with chronic tic disorders . © 2005 Wiley‐Liss , We analyzed the putative functional promoter polymorphism of the serotonin transporter ( 5-HTTLPR ) in two large autism spectrum disorder sample s and a control sample . A Hardy-Weinberg disequilibrium was detected for 5-HTTLPR in the unaffected founders of both autism spectrum disorder sample s and control sample s. When we lowered the total magnesium concentration in the polymerase chain reaction below levels reported in previously published studies , we observed a shift in relative allele frequencies and restoration of the Hardy-Weinberg equilibrium . Our data suggest that higher magnesium concentrations caused allele-dependent , non-r and om genotyping errors . Genotyping data obtained from the 2 mM magnesium protocol increased the significance of linkage and gave suggestive ( P=0.06 ) association with  autism spectrum disorder , whereas the corrected genotypes of 5-HTTLPR provide no linkage information beyond the results we have previously published and no evidence of association with autism spectrum disorder . We present details regarding appropriate polymerase chain reaction conditions for the accurate genotyping of this polymorphism UNLABELLED Previous studies of serotonin transporter protein ( 5HTPR ) indexed in platelets by 3H-imipramine demonstrate reduction in children with comorbid obsessive-compulsive disorder ( OCD ) and Tourette 's syndrome ( TS ) . OBJECTIVE To use the 5HTPR selective lig and 3H-paroxetine and homogeneous diagnostic groups to reevaluate these findings . METHOD Platelet Kinetic binding parameters were evaluated using st and ard techniques from medication-free child and adolescent patients with OCD ( n = 18 ) , with TS ( n = 10 ) , and normal controls ( n = 19 ) . RESULTS Baseline binding capacity ( Bmax ) was significantly reduced in patients with OCD ( 1,342 + /- 952 fmol/mg ; protein p < .01 ) compared with normal controls ( 2,486 + /- 1309 fmol/mg ) and TS patients ( 2,420 + /- 1,069 fmol/mg ; p < .05 ) . Among OCD patients who were subsequently treated on an open-label basis with selective serotonin reuptake inhibitor ( SSRI ) , Bmax values at baseline differentiated between responders ( 1,718 + /- 1,041 fmol/mg ) and nonresponders ( 802 + /- 713 fmol/mg protein ; p < .05 ) . Response to SSRI was greatest in patients with a positive family history of OCD . Among responders ( n = 10 ) , baseline Yale-Brown Obsessive Compulsive Scale and Bmax were positively correlated ( r = .76 , p = .01 ) , as was Clinical Global Impression ( r = .67 , p = .03 ) . CONCLUSIONS Platelet 5HTPR capacity ( Bmax ) is reduced in children and adolescents with OCD , but not in those with TS . 5HTPR may be an indirect measure of basal serotonergic tone Peripheral measures of serotonergic and noradrenergic function were obtained in 29 obsessive-compulsive adolescents and 31 age- and sex-matched controls , as well as in a sub sample of 22 patients after five weeks of treatment with clomipramine hydrochloride ( 134 + /- 33 mg/d ) ( mean + /- SD ) given in a double-blind placebo-controlled trial . Drug-free obsessive-compulsive subjects did not differ from controls on measures of platelet serotonin and monoamine oxidase ( MAO ) activity , nor on plasma epinephrine or norepinephrine concentrations at rest and after a st and ard orthostatic challenge procedure . Compared with placebo , treatment with clomipramine was clinical ly effective and produced a marked decrease in platelet serotonin concentration , a trend toward a reduction in platelet MAO activity , and a rise in st and ing plasma norepinephrine . Clinical improvement during drug therapy was closely correlated with pretreatment platelet serotonin concentration and MAO activity , as well as with the decrease in both measures during clomipramine administration . This suggests that the effects of clomipramine on serotonin uptake may be essential to the antiobsessional action observed Family and twin studies have supported a strong genetic factor in the etiology of obsessive‐compulsive disorder ( OCD ) , although the precise mechanism of inheritance is unclear . Clinical and pharmacological studies have implicated the serotonergic and dopaminergic systems in disease pathogenesis . In this cross‐sectional study , we have examined the allelic and genotypic frequencies of a Val‐158‐Met substitution in the COMT gene , a 44‐base pair ( bp ) length variation in the regulatory region of the serotonin transporter gene ( 5‐HTTLPR ) and the T102C and C516 T variants in the serotonin receptor type 2A ( 5HT2A ) gene in 79 OCD patients and 202 control subjects . There were no observed differences in the frequencies of allele and genotype between patients and control groups for the COMT , the 5HTTLPR and the T102C 5HT2A gene polymorphisms . In contrast , a statistically significant difference between OCD patients and controls was observed on the genotypic distribution ( χ2 = 16.7 , 2df , P = 0.0002 ) and on the allelic frequencies ( χ2 = 15.8 , 1df , P = 0.00007 ) for the C516 T 5HT2A gene polymorphism . The results suggest that the C516 T variant of the 5HT2A gene may be one of the genetic risk factors for OCD in our sample . However , further studies using larger sample s and family based methods are recommended to confirm these findings 
    Output:
    
In the overall meta- analysis we found no evidence of association between genetic variation at the 5-HTTLPR locus and OCD .
In the stratified meta-analyses , we demonstrated a significant association between the l-allele and OCD in family-based association studies and in studies involving children and Caucasians .
Our meta- analysis suggests the possibility that the l-allele may be associated with OCD in specific OCD subgroups such as childhood-onset OCD and in Caucasians .
Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset , gender and the presence of comorbid illness ( e.g. , tics ) moderates the relationship between 5-HTTLPR and OCD