5-羟色胺转运体基因与注意缺陷多动障碍及其相关症状的关联分析

目的　探讨5- 羟色胺转运体( 5 -HTT)基因启动子区多态性与注意缺陷多动障碍(ADHD)及其相关症状的关系。方法　抽取1 39例ADHD患儿及1 1 5名正常对照,用Achenbach儿童行为调查表(CBCL)来评定患者的临床症状;采用聚合酶链式反应(PCR)、聚丙烯酰胺凝胶电泳结合银染技术,检测ADHD患者和对照组基因型和等位基因的频率。结果　患者组5- HTT启动子区多态性( 5- HTTLPR)的基因型和等位基因的频率与对照组相比无显著性差异(P >0. 0 5) ;但发现S/S基因型个体社会退缩、躯体主诉两行为分量表评分高,S/S基因型个体与S/L +L/L基因型个体间社会退缩、躯体主诉两分量表分有显著性差异(P <0 . 0 5)。结论　本研究结果不支持5- HTTL- PR与ADHD存在关联,但ADHD的某些内化性症状与5 -HTTLPR可能存在关联。     

A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment

Although attention-deficit/hyperactivity disorder (ADHD) is highly heritable, environmental conditions play an important role in its manifestation during childhood development. Here, we report the results of an investigation on the interaction of adverse childhood environment with a functional polymorphism of the serotonin transporter promoter gene (5-HTTLPR) and its impact on ADHD psychopathology in young adult delinquents. Standardized instruments were used to assess childhood and current ADHD and adverse childhood environment in 184 male delinquents. Each subject was genotyped for 5-HTTLPR long (L) and small (S) alleles. Logistic regression analysis revealed independent effects of high childhood environmental adversity and the 5-HTTLPR LL-genotype on self-reported childhood ADHD and on persistent ADHD. In addition, a significant gene by environment interaction was found, indicating that carriers of at least one 5-HTTLPR short allele are more sensitive to childhood environment adversity than carriers of the LL-genotype. The results support prior findings of association between ADHD and 5-HTTLPR LL-genotype and adverse childhood environment, and they underline the need for further investigation of gene by environment interaction with respect to ADHD.     

Association analysis of serotonin transporter promoter gene polymorphism with ADHD and related symptomatology

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop attention deficit hyperactivity disorder. Several investigations have reported associations between ADHD and serotonin transporter promoter polymorphisms, but the results have been inconsistent. The present study did not find significant association between ADHD and serotonin transporter promoter polymorphisms, but did find an effect of serotonin transporter promoter polymorphisms on some ADHD symptomatology. Patients homozygous for the short allele showed more Withdrawn or Somatic complaint scores than subjects with the long allele.     

5-羟色胺转运体基因多态性与青少年抑郁症的关联研究

目的 探讨中国汉族青少年抑郁症与5-羟色胺转运体（5-HTY）基因的启动子区多态（5-HTTLPR）之间的关系。方法 应用聚合酶链式反应（PCR）扩增技术对84例青少年抑郁症患者和85例健康者进行基因型分析。结果 5-HTYLPR基因的3种基因型S／S,L／S和L/L在青少年抑郁症组的分布分别为57．1％,36．9％,6．0％;在对照组分别为57．6％,34．1％,8．2％,两组间差异无显著性（P〉0．05）。抑郁症组中S／S基因型患者HAMD自杀因子评分明显高于L／L和L／S型患者（P〈0.01）。结论 5-HTT基因多态性与青少年抑郁症无明显关联。抑郁症中携带S／S基因型患者的自杀风险相对比L／L型、L／S型患者高。     

The relationship between serotonin transporter gene promoter polymorphism and serum lipid levels at young age in a longitudinal population-representative study

The serotonin transporter gene promoter region polymorphism (5-HTTLPR) has been linked to psychiatric disorders, mostly anxiety and affective disorders. In elderly populations 5-HTTLPR polymorphism has also been reported to be associated with serum lipid levels. We have examined the interaction of the 5-HTTLPR polymorphism and the markers of lipid metabolism at young age in a longitudinal, population-representative cohort study. The sample of the Estonian Children Personality Behaviour and Health Study (initially cohorts of 9 and 15 year old children, complete lipid and genotype data for n = 1176) was examined throughout 10 years. Subjects were genotyped and the levels of low-density lipoproteins, high-density lipoproteins, triglycerides, and total cholesterol were measured. Children and adolescents carrying the s allele of the 5-HTTLPR polymorphism had lower levels of low-density lipoprotein and total cholesterol. At the age of 25, the s allele carriers had higher levels of high-density lipoproteins. These associations were independent of gender. Thus the 5-HTTLPR can be associated with the serum lipid levels and in particular low-density lipoproteins already in a young age.     

Serotonin transporter gene polymorphism and the phenotypic heterogeneity of adult ADHD

Summary The present study investigates possible associations between the 5-HTT control region polymorphism (5-HTTLPR) with adult ADHD, including subtypes, severity, temperament profile and comorbidities. The polymorphic site was genotyped in 312 adult patients with ADHD and 236 controls, all of them Brazilians of European descent. The interviews followed the DSM-IV criteria, using the K-SADS-E for ADHD and oppositional defiant disorder, SCID-I and MINI for comorbidities and the TCI for temperament dimensions. The 5-HTTLPR polymorphism was not associated with ADHD. Carriers of the S allele presented slightly higher inattention and novelty seeking scores, and a higher frequency of drug dependence. These differences do not persist after correction for multiple comparisons. These results suggest that the 5-HTTLPR polymorphism does not have a direct role in the predisposition to adult ADHD. There is suggestive evidence for a small effect in some behavioral phenotypes related to ADHD.     

The impact of adverse life events and the serotonin transporter gene promoter polymorphism on the development of eating disorder symptoms

Adverse life events have been shown to predict weight fluctuations and dietary restraint, as well as eating disorders during adolescence or early adulthood. Since the s-allele carriers of the 5-HTT gene-linked polymorphic region (5-HTTLPR) are biologically more reactive to stress related stimuli, we aimed to explore whether the eating disturbances are predicted by environmental stressors and moderated by the 5-HTTLPR genotype. The sample was based on the younger cohort of the Estonian Children Personality, Behaviour and Health Study and included those participating in its second and third wave. The history of stressful life events was self-reported at age 15. Data on eating behaviour and attitudes, anxiety, impulsivity and depressiveness were collected at age 18. The effect of the adverse life events on binge eating and on drive for thinness was found to be moderated by the 5-HTTLPR. Adolescent girls who at age 15 had reported a history of frequent adverse life events had elevated scores in EDI-2 Bulimia subscale at age 18 if they were carrying the s-allele. The effect of the s-allele on binge eating was even more pronounced when solely the experience of sexual abuse was considered. The interaction effect of the 5-HTTLPR and the past sexual abuse was also observed on drive for thinness. These data give further support to the idea that adverse life events in childhood may heighten susceptibility to serotonergic dysregulation following stress, and suggest that in individuals vulnerable to eating disorders this may result in disturbed eating behaviours.     

The developmental course of childhood inattention symptoms uniquely predicts educational attainment: A 16-year longitudinal study

In this 16-year longitudinal study, a new trajectory estimation approach was used to verify whether the developmental course of childhood inattention significantly predicted functional impairment. A rising childhood inattention trajectory significantly predicted graduation failure (OR: 1.76 [1.32–2.34]) independently of averaged inattention levels. Rising inattention is, in itself, important for prognosis.     

5-羟色胺转运体基因多态性与精神分裂症的相关性研究

目的：探讨中国汉族人群中5一羟色胺转运体（5-HTT）基因与精神分裂症之间的相关性。方法：189例符合中国精神障碍分类与诊断标准第3版及美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者（患者组）使用聚合酶链式反应扩增5-HTT基因的启动子区（5-HTrLPR）位点和内含子区（5-HTTVNTR）位点,以琼脂糖凝胶电泳分离法进行基因分型,并和300名正常人（正常对照组）进行对照。结果：患者组与正常对照组之间5-HTTLPR位点L／L、L／S和S／S基因型频率以及等位基因L、s频率分布上差异具有统计学意义（x2=47．882,x2=44．188;P〈0．01或P〈0．001）;5-HTTVNTR位点12／12、12／10、10／10基因型频率和等位基因10、12频率分布上差异无统计学意义（X2=0．335,X。=0．051;P均〉0．05）。结论：S／S基因型及S等位基因可能是精神分裂症患者的易感等位基因;5-HT．TVNTR位点在中国汉族人群精神分裂症发病机制中可能不起主要作用。     

Relationships between serotonin transporter promoter polymorphism, platelet serotonin transporter binding and clinical phenotype in suicidal and non-suicidal adolescent inpatients

Summary. Relationships between the serotonin transporter promoter polymorphism (5-HTTLPR), platelet serotonin transporter (SERT) binding and clinical phenotype were examined in 32 suicidal and 28 non-suicidal Ashkenazi Israeli adolescent psychiatric inpatients. The 5-HTTLPR polymorphism was not associated with transporter binding or with suicidality or other clinical phenotypes. However, in the suicidal group, a significant positive correlation between platelet SERT density and anger scores (n=32, r=.40; p=.027) and a negative correlation between platelet count and trait anxiety (n=32, r=–.42; p=.034) were observed.     

5-羟色胺基因多态性与抑郁症的相关性研究

目的：探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与抑郁症的相关性及其对抗抑郁药疗效的影响。方法：运用聚合酶链反应技术(PCR)检测51例抑郁症患者(患者组)和60名健康对照者(对照组)5-HTTLPR的分布频率；并予文拉法辛治疗，用汉密尔顿抑郁量表(HAMD)观察疗效。结果：患者组5-HTTLPR的短重复序列／短重复序列(short／short，S／S)基因型和短重复序列(short，S)等位基因频率分别为71％和81％，对照组为45％和69％差异显著。治疗4周后，长重复序列／长重复序列(long／long，L／L)基因型患者的减分率显著高于其他两型。结论：5-HTTLPR的S／S基因型可能是抑郁症的易感基因之一，L／L基因型可能和更好的选择性5-羟色胺受体阻滞剂类(SSRIs)疗效有关。     

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism.

BACKGROUND: A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS: SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS: Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS: Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.     

Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis.

BACKGROUND: There is strong evidence supporting a role for serotonin system dysfunction in the pathology of suicidal behavior. Many studies have examined the association between a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) and suicide but have yielded inconsistent results. Our goal here, by analyzing the cumulative data from primary literature, was to determine conclusively whether there is an association. METHODS: Three meta-analyses were performed. One compared the 5-HTTLPR polymorphism between suicidal subjects and normal control subjects; another compared suicide attempters with nonattempters of the same psychiatric diagnoses; the last one compared either violent or nonviolent suicidal subjects with normal control subjects. RESULTS: We found no association between 5-HTTLPR polymorphism and suicidal behavior (p =.379). When we compared subjects with the same psychiatric diagnoses, the genotypes carrying the s allele were significantly more frequent in suicide attempters than in nonattempters (p =.004). In addition, the s allele was associated with violent suicide (p =.0001) but not with nonviolent suicide (p = 1.00). CONCLUSIONS: Our results provide significant evidence supporting the association of the s allele of 5-HTTLPR polymorphism with suicidal behavior in the psychiatric population, also with violent suicide. These support a role for decreased serotonin transporter function in the vulnerability to suicide in a select population.     

A serotonin transporter gene polymorphism predicts peripartum depressive symptoms in an at-risk psychiatric cohort

Backgroud

Peripartum major depressive disorder (MDD) is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population.

Methods

Two hundred and seventy four women with a prior history of MDD were genotyped for 5-HTTLPR and serially evaluated in late pregnancy (gestational weeks 31-40), early post-partum (week 1-8) and late post-partum (week 9-24) for diagnosis of a current major depressive episode (MDE) and depressive symptom severity.

Results

5-HTTLPR S-allele carrier status predicted the occurrence of a MDE in the early post-partum period only (OR = 5.13, p = 0.017). This association persisted despite continued antidepressant treatment.

Conclusions

The 5-HTTLPR genotype may be a clinically relevant predictor of early post-partum depression in an at-risk population.

Objective

Peripartum major depressive disorder is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population.     

Influence of the serotonin transporter promoter gene polymorphism on susceptibility to posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by behavioral, physiologic, and hormonal alterations. The etiology of PTSD is unknown, although exposure to a traumatic event constitutes a necessary, but not sufficient, factor. Serotonergic dysfunction has been implicated in PTSD. The present study examined the possible association between the serotonin-transporter-linked polymorphic region (SERTPR) and PTSD. The genotype and allele frequencies of the SERTPR were analyzed in 100 PTSD patients and 197 unrelated healthy controls using a case-control design. The frequency of the s/s genotype was significantly higher in PTSD patients than in normal controls. These findings suggest that the SERTPR s/s genotype is one of the genetic factors for the susceptibility to PTSD. Further investigations are required into the influence of gene polymorphisms on the biological mechanisms of PTSD, its clinical expression, and its response to treatment.     

The serotonin transporter gene polymorphism and the effect of baseline on amygdala response to emotional faces

Previous research has found that a common polymorphism in the serotonin transporter gene (5-HTTLPR) is an important mediator of individual differences in brain responses associated with emotional behaviour. In particular, relative to individuals homozygous for the l-allele, carriers of the s-allele display heightened amygdala activation to emotional compared to non-emotional stimuli. However, there is some debate as to whether this difference is driven by increased activation to emotional stimuli, resting baseline differences between the groups, or decreased activation to neutral stimuli. We performed functional imaging during an implicit facial expression processing task in which participants viewed angry, sad and neutral faces. In addition to neutral faces, we included two further baseline conditions, houses and fixation. We found increased amygdala activation in s-allele carriers relative to l-homozygotes in response to angry faces compared to neutral faces, houses and fixation. When comparing neutral faces to houses or fixation, we found no significant difference in amygdala response between the two groups. In addition, there was no significant difference between the groups in response to fixation when compared with a houses baseline. Overall, these results suggest that the increased amygdala response observed in s-allele carriers to emotional faces is primarily driven by an increased response to emotional faces rather than a decreased response to neutral faces or an increased resting baseline. The results are discussed in relation to the tonic and phasic hypotheses of 5-HTTLPR-mediated modulation of amygdala activity.     

5-羟色胺转运体启动子区基因多态性与强迫症的关联分析

目的:探索汉族人群中的5-羟色胺转运体启动子区(5-HTTLPR)基因多态性与强迫症的发病关系.方法:对强迫症患者(强迫症组)和正常对照者(对照组)分别采用聚合酶链反应扩增片断长度多态技术测定基因型.结果:强迫症组与对照组5-HTTLPR的基因型频率无显著性差异;两组的等位基因频率有显著性差异.L等位基因与强迫症呈正关联(OR=1.929,P＜0.05).结论:5-HTTLPR基因多态性的L等位基因与强迫症相关联,是强迫症的危险因子.     

A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism

According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.     

The serotonin transporter gene: polymorphism and haplotype analysis in Russian suicide attempters

The focus on gender-specific genes associated with female suicide is justified by the possible dimorphic nature of the serotonergic system and by the greater number of suicide attempts in females. We performed analysis of the promoter (5-HTTLPR) and intron 2 (STin2 VNTR) polymorphisms and haplotypes of the serotonin transporter gene in Russian suicide attempters, separately in men and women. Our findings indicate the contribution of the SLC6A4 gene to susceptibility for suicidal behavior in women, but not in men. The L/L genotype (p = 0.013, OR = 2.09) and L10 haplotype (p = 0.04, OR = 1.77) were associated with suicide in Russian women only. Further investigations of this gene in different phenotypic groups are necessary.