No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.     

5—HT6受体基因多态性与阿尔茨海默病的关联分析

目的探讨中国上海地区汉族人群中5-HT6受体基因多态性与阿尔茨海默病(AD)的相互关系.方法应用聚合酶链式反应(PCR)-限制性片段长度多态性(RFLP)方法,在106例AD患者,87例血管性痴呆(VD)患者和140例正常健康人中观察了5-HT6受体基因多态性的分布,并对5-HT6受体基因多态性与阿尔茨海默病之间的关系进行探讨.结果①阿尔茨海默病与5-HT6受体基因的多态性之间无显著意义的关联(P＞0.05);②在将受试人群进行ApoE基因分型后,ApoEε4型与非ApoEε4型人群中AD与5-HT6受体基因各基因型或等位基因均无关联(P＞0.05);③将AD患者进行ApoE基因分型后,非ApoEε4型AD与5-HT6的267C/T基因型正相关(OR=2.46,95%CI5.43-1.11,P＜0.05).结论中国上海地区汉族人群中5-HT6受体基因多态性与非ApoEε4型阿尔茨海默病相关联,表现为C/T型频率的升高.     

T102C polymorphisms at the 5-HT2A receptor gene in Turkish schizophrenia patients: a possible association with prognosis

BACKGROUND: Serotonergic system abnormalities have been implicated in the pathogenesis of schizophrenia. The 5-HT2A receptor gene polymorphism has long been implicated to play a role in the pathogenesis of schizophrenia. AIM: In this study, we assessed the relationship of schizophrenia and its subgroups with 5-HT2A receptor gene polymorphism, and attempted to evaluate a possible correlation between the severity and prognosis of the illness and 5-HT2A receptor gene polymorphism. METHOD: Our study comprised 141 unrelated subjects who strictly met DSM-IV criteria for schizophrenia, and 79 healthy unrelated controls, all of Turkish origin. A clinical evaluation of all patients was accomplished applying the Brief Psychiatric Rating Scale (BPRS) test. The analysis of 5-HT2A receptor gene polymorphism was performed using the polymerase chain reaction technique. RESULTS: Regarding 5-HT2A receptor gene polymorphisms, no statistically significant difference was found between schizophrenic patients and control subjects (p > 0.05). There was no significant difference between the average of BPRS points of the patients and 5-HT2A receptor gene polymorphisms (p > 0.05). Although there was no correlation between the duration of illness and polymorphism (p > 0.05), the frequency of hospitalization was found to be higher in the patients with T/C and T/T genotypes compared with the patients with C/C genotype (p < 0.05). CONCLUSION: Our findings indicate that the T102C polymorphisms of the 5-HT2A receptor gene does not play a substantial role in schizophrenia nor help evaluate susceptibility to schizophrenia. Since the 5-HT2A receptor gene polymorphism is associated with the frequency of hospitalization of the patients, it may be an indicator of prognosis in schizophrenia or help differentiate the patients who are somewhat refractory to antipsychotic treatment.     

Association analysis for the C-1019G promoter variant of the 5-HT1A receptor gene with auditory evoked potentials in major depression

Involvement of the serotonergic system in N1 and P2 components of auditory evoked potentials (AEPs) has been implicated. Moreover, studies have indicated the presence of heritability in the genesis of AEP components. The serotonin 1A (5-HT1A) receptor gene is a strong candidate for N1 and P2 components of the AEPs because 5-HT1A receptor regulates the firing of serotonergic neurons. The present study tested the hypothesis that the 5-HT1A promoter genetic polymorphism (C-1019G) is associated with N1 and P2 components of AEPs in unmedicated major depression patients. The sample consisted of 221 Chinese patients (mean age: 44.3 years; male/female: 93/128) diagnosed with major depression. AEPs and 5-HT1A genotyping were done for each patient. Patients with the C/C genotype had a significantly shorter P2 latency when compared with C/G or G/G genotype patients (p = 0.049), and the difference in P2 latency was significant among the 5-HT1A genotype groups in male patients (p = 0.031) but not in female patients (p = 0.398). These findings suggest that this 5-HT1A polymorphism may affect AEP P2 latency in a gender-dependent manner. Further studies with other genetic polymorphisms in the serotonergic system may help to clarify the relation between serotonergic function and AEP components.     

Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer disease

BACKGROUND: Serotonin has been linked to neuropsychiatric symptoms in Alzheimer disease, mainly agitation/aggression, depression, and psychosis. Neuropsychiatric symptoms have been associated with polymorphisms of the promoter region (5-HTTPR ) and intron 2 of the serotonin transporter gene (5-HTTVNTR) or the 5-HT2A and 5-HT2C receptor genes in some but not all studies. OBJECTIVE: To examine the association of the serotonin promoter, transporter, and receptor genes with neuropsychiatric symptoms in patients with Alzheimer disease. METHODS: The sample included 96 patients with Alzheimer disease from the outpatient clinic of the University of California Los Angeles Alzheimer's Disease Research Center, Los Angeles. The Neuropsychiatric Inventory was used to measure neuropsychiatric symptoms, and blood samples were available for genetic analysis. Based on the literature, we hypothesized that the 5-HT2A and 5-HT2C receptor polymorphisms would be associated with agitation/aggression and psychosis and the 5-HTTPR or 5-HTTVNTR polymorphisms, with agitation/aggression or depression and anxiety. One-way analyses of variance were performed with age, ethnicity, sex, or education as covariates. RESULTS: The 102T genotype of the 5-HT2A receptor was significantly associated with delusions (P =.045) and agitation/aggression (P =.002). We did not replicate previous associations of the 5-HT2C receptor polymorphism with psychosis or of the 5-HTTPR polymorphism with agitation/aggression, psychosis, or depression. We did not find any associations with the 5-HTTVNTR polymorphism and agitation/aggression, depression, or anxiety. CONCLUSIONS: The 5-HT2A receptor polymorphism may contribute to the expression of psychosis and agitation/aggression in patients with Alzheimer disease. Absence of other positive associations may be due to the relatively small sample size and/or potentially small effect size of the polymorphisms and requires further study.     

5-HT1B基因A161T多态性与抑郁症的关联研究

目的探讨抑郁症患者与5-HT1B受体基因A161T多态性之间的关系。方法应用聚合酶链式反应（PCR）扩增技术及限制性片段长度多态性（arLP）分别检测365例抑郁症患者（病例组）、365名健康人（对照组）的5-HT1B受体基因A161T多态性。结果5-HT1B受体基因A161T多态性在病例组和对照组的基因型和等位基因分布频率无显著性差异；按照发病年龄（30岁为界）、有无家族史及有无自杀观念分层后，各亚组与对照组间基因型和等位基因分布也无显著性差异。经多因素分析控制年龄、性别因素后各组基因型分布仍无显著性差异。结论5-HT1B受体基因A161T多态性可能不是抑郁症及其各临床亚型发病的一个危险因素。     

T102C and -1438 G/A polymorphisms of the 5-HT2A receptor gene in Turkish patients with obsessive-compulsive disorder.

OBJECTIVE: This study aimed to investigate the possible association between T102C and -1438 G/A polymorphism in the 5-HT2A receptor gene and susceptibility to and clinical features of obsessive-compulsive disorder (OCD). METHOD: Fifty-eight patients with OCD and 83 healthy controls were included in the study. All patients were interviewed and rated by Yale-Brown Obsessive-Compulsive Scale. T102C and -1438 G/A polymorphisms of 5-HT2A receptor gene were determined by PCR technique in DNAs of peripheral leucocytes. RESULTS: OCD patients and healthy controls did not show significant differences in genotype distribution for both polymorphisms investigated. We found that frequencies of the TT genotype for T102C polymorphism and the AA genotype for -1438 G/A polymorphism were significantly higher in patients with severe OCD compared to those with moderate or moderate-severe OCD. CONCLUSION: The -1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with an increased risk of OCD. Our data suggest that the TT genotype of T102C and the AA genotype of -1438 G/A polymorphism might be a factor in clinical severity of OCD.     

Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene.

BACKGROUND: The pathophysiology of tardive dyskinesia (TD) is not completely understood.Aim. - To assess the relationship of TD with 5-HT2A receptor gene, serotonin transporter gene (5 HTT), and catechol-o-methyltransferase (COMT) gene polymorphisms. METHOD: Our study comprised 111 unrelated subjects who strictly met DSM-IV criteria for schizophrenia and 32 TD, and 79 healthy unrelated controls; all the subjects were of Turkish origin. The analyses of 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were performed using polymerase chain reaction (PCR) technique. RESULTS: The polymorphisms of these genes were not significantly different between the schizophrenic patients, TD and control subjects. CONCLUSION: Our findings indicated that 5-HT2A receptor gene, 5 HTT gene, and COMT gene polymorphisms were similar in schizophrenia with non-TD, schizophrenia with TD, and healthy controls. These polymorphisms, though, do not help to evaluate the susceptibility to TD.     

5-羟色胺2A受体基因多态性与利培酮治疗中国首发精神分裂症患者疗效关联

背景5-羟色胺2A受体基因已经证实为精神分裂症的候选易感基因,因为阐明其作为非典型抗精神病药物重要作用靶点减轻阴性症状已引起业界倍加关注.本研究试图探讨(1)5-HT2A受体基因T102C多态性在不同临床亚型之间等位基因和基因型频率的关系,(2)5-HT2A受体基因T102C在利培酮高剂量组和低剂量组之间基因型和等位基因分布频率的关系,(3)5-HT2A受体基因T102C多态性在治疗有效组与无效组之间的基因型和等位基因分布频率的关系,(4)5-羟色胺2A受体T102C基因多态性是否与中国首发精神分裂症患者利培酮疗效有关.方法对201例精神分裂症初发期患者分别进行利培酮治疗[3～5 mg/d,平均(3.2±1.3)mg/d],疗程8周.采用聚合酶链式反应扩增与限制性片段长度多态性(PCR-RFLP)技术检测5-HT2A受体基因T102C多态性.以临床亚型将精神分裂症患者划分为偏执型、瓦解型、未定型和其他型,分析不同临床亚型等位基因和基因型频率的差异;按服用利培酮剂量划分低剂量组(＜4 mg/d)和高剂量组(≥4 mg/d),经比较利培酮高剂量组和低剂量组的5-HT2A受体基因T102C基因型和等位基因分布频率差异性;同时以阴性和阳性症状量表(PANSS)总减分率＞50%有效,≤50%为无效以分析治疗有效组与无效组之间的基因型和等位基因分布频率差异有无显著性;以PANSS评定患者治疗前及治疗后2周、4周、6周和第8周末的精神症状,比较5-HT2A受体T102C各基因亚型与年龄、发病年龄、PANSS总分值、阳性症状基线分、阴性症状基线分、一般病理症状基线分、PANSS总减分率、阳性症状减分率、阴性症状减分率和一般病理症状减分率的差异.结果5-HT2A受体T102C基因型在患者组分布频率均符合H-W平衡定律(P＞0.05);不同临床诊断亚型精神分裂症患者等位基因和基因型频率无显著性差异(χ2=0.415,P=0.937;χ2=1.705,P=0.941);高剂量组与低剂量组之间的基因型和等位基因分布频率差异均无显著性(χ2=2.402,P=0.301;χ2=2.465,P=0.116);治疗有效和无效组的基因型和等位基因分布频率的差异无显著性(χ2=1.995,P=0.369;χ2=1.939,P=0.164);各基因型亚组的年龄、发病年龄及其病程差异均无显著性(P均大于0.05);但基因亚组A1/A1的治疗前PANSS总分(χ2=4.076,P=0.018)和阴性症状分(χ2=3.946,P=0.021)以及治疗结束PANSS总分减分率(χ2=4.036,P=0.019)和阴性症状减分率(χ2=3.876,P=0.022)均显著高于A1/A2及A2/A2基因型.结论(1)首发精神分裂症患者不同临床亚型5-HT2A受体基因T102C基因型和等位基因频率无显著差异.(2)利培酮高剂量组和低剂量组5-HT2A受体基因T102C基因型和等位基因分布频率没有显著性差异.(3)治疗有效组与无效组之间5-HT2A受体基因T102C基因型和等位基因分布频率也无显著性差异.(4)5-HT2A受体T102C Ai/A1基因亚型可能影响中国首发精神分裂症患者对利培酮的治疗效应.     

5-羟色胺2A受体基因多态性与抑郁症的关联

目的：探讨中国汉族人群难治性抑郁症患者与5-羟色胺2A(5-HT2A)受体基因的T102C多态性之间的关系。方法：抽取79例难治性抑郁症患者作研究，以102名正常人作对照。应用聚合酶链式反应(PCR)扩增技术及限制性片段长度多态性(RFLP)分别测定所有研究对象的5-HT2A受体基因的基因型和等位基因。结果：5-HT2A受体基因的3种基因型(A1／A1，A1／A2和A2／A2)在难治性抑郁症组的分布分别为31．6％、54．4％和13．9％，在对照组分别为29．4％、45．1％和25．5％，两组间差异无显著性。结论：5-HB。受体基因的T102C多态性与难治性抑郁症之间无显著关联。     

Involvement of an altered 5-HT -{6} receptor function in behavioral symptoms of Alzheimer's disease

We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT_{6} receptor agonist E-6801 was significantly lower (p<0.01) in AD (170.02 +/- 27.53 pmol/mg prot.) compared to controls (823.33 +/-196.67). In addition, the ratio cAMP formation after stimulation with E-6801/5-HT_{6} receptor density was significantly lower (p< 0.01) in AD (6.67 +/- 0.83) compared to controls (16.67 +/- 3.33). Splitting these results by sex, 5-HT_{6} receptor activation was significantly lower (p< 0.01) in AD females compared to males (121.67 +/- 30.02 vs. 231.67 +/- 34.17 pmol/mg prot). 5-HT_{6} density and 5-HT levels were significantly correlated (p < or = 0.01) in both controls and AD patients, although in AD, this correlation was lost in females. Psychosis factor was the best predictor of reduced 5-HT levels or adenylate cyclase activity after E-6801 stimulation, the former result being due to females. It may be suggested that psychotic symptoms may be related to a dysregulation of 5-HT_{6} activation by 5-HT in the temporal cortex. These results are discussed in terms of purported influence of sex and therapeutical approaches to psychosis in AD.     

Prefrontal executive function and D1, D3, 5-HT2A and 5-HT6 receptor gene variations in healthy adults

OBJECTIVE: The Val158Met polymorphism of the catechol-O-methyltransferase gene has been demonstrated to be associated with prefrontal executive function explaining 4% of variance in perseverative errors on the Wisconsin Card Sorting Test (WCST). Studies suggest that dopamine D(1) and D(3) and serotonin 5-HT(2A) and 5-HT(6) receptors may also be involved in prefrontal cognitive function and that genetic polymorphisms (D(1) A-48G, D(3) Ser9Gly, 5-HT(2A) T102C, and 5-HT(6) T267C) of these receptors may be associated with brain glucose metabolism or neurophysiological function. The current study's objective was to investigate whether executive function varies with these genetic variations. METHODS: A sample of 216 healthy Han Chinese adults were measured with the WCST and genotyped for the 4 genetic polymorphisms. RESULTS: Kruskal-Wallis tests showed a significant difference in WCST perseverative errors among the genotypes D(3) Ser9Gly (p = 0.009), 5-HT(2A) T102C (p = 0.038) and 5-HT(6) T267C (p = 0.010), but not in the genotype D(1) A-48G. Multiple regression analysis for the WCST natural logarithm values (i.e., for fulfilling the normal distribution requirement) showed that subjects' perseverative errors were significantly influenced by D(1) A-48G, D(3) Ser9Gly, 5-HT(2A) T102C and 5-HT(6) T267C polymorphisms after adjustment of other variables. CONCLUSION: The preliminary data suggest that D(1), D(3), 5-HT(2A) and 5-HT(6) genetic mutations may influence prefrontal executive cognition in healthy adults. Further studies in larger samples with other ethnicities or in mentally ill patients are warranted.     

精神分裂症与5—HT2A受体基因相关联

目的：探讨中国汉族人群精神分裂症与5－HT2A受体基因T102C多态性之间的关系。方法：选择精神分裂症患者286例,按病期分一般组和慢性组;以291例正常人对照,也按现年龄相应地分为一般对照组和慢性对照组,分生物学技术采用PCR扩增及MSPI内切酶酶切技术,检测各组研究对象的5－HT2A受体基因的基因型和等位基因的频率分布,结果：一般组精神分裂症患者5－HT2A受体基因A2／A2型频率及A2等位基因频率均显著高于对照组（ZA2／A2＝2．97,P＜0．05;ZA2＝2．19,P＜0．05）。经关联分析,其OR值分别为2．35（P＜0．05）和1．45（P＜0．05）。结论：提示中国汉族人群中5－HT2A受体基因多态性可能与精神分裂症呈正关联,而与慢性精神分裂症无关联。     

同胞精神分裂症与5-羟色胺2A受体基因的关联分析

目的 探讨慢性精神分裂症患者的受累同胞和散发性精神分裂症与5-羟色胺2A受体基因(5-HT2A)T102C多态性的关联。方法 先用严格的纳入标准收集共患慢性精神分裂症的同胞60对(120例)和散发性精神分裂症120例,分别与正常同胞60对(120名)和120名正常人对照,采用聚合酶链反应(PCR)扩增及MspI内切酶酶切技术,检测各组的5-HT2A受体基因的基因型和等位基因的频率分布。结果 60对共患慢性精神分裂症的受累同胞组5-HT2A受体基因A1／A1基因型频率显著高于正常同胞组(X2=5.58,P<0.05),经配对比较,患者同胞组共有A1／A1基因型也显著多于正常同胞组(X2=3.94,P<0.05),而散发性精神分裂症与正常人对照组各基因型和等位基因的构成差异均无显著性意义。结论 共患慢性精神分裂症的同胞与5-HT2A受体基因A1／A1型关联,A1／A1纯合子易患精神分裂症,散发性精神分裂症可能与5-HT2A受体基因无关联。     

Association between Serotonin-Related Polymorphisms in 5HT2A, TPH1, TPH2 Genes and Bipolar Disorder in Korean Population

Objective

The aim of the present study was to examine the association between serotonin-related gene polymorphisms and bipolar disorder in the Korean population. In addition, we sought to explore the relationship between the clinical characteristics of bipolar patients and serotonin-related gene polymorphisms.

Methods

Inpatients with bipolar disorder (n=103) and control subjects (n=86) were genotyped for 5HT2A 1438A/G, tryptophan hydroxylase 1 (TPH1) 218 A/C, and TPH2 703G/T. We divided patients with bipolar disorder into two groups according to the presence of psychotic symptoms. The severity of their symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS).

Results

There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between patients with bipolar disorder and normal controls. There were significant differences in genotype distributions and allele frequencies of the 5-HT2A -1438A/G polymorphism between the psychotic mania group and the non-psychotic mania group (genotype: χ²=7.50, p=0.024; allele: χ²=5.92, p=0.015). However, after Bonferroni correction this signifact difference disappeared. We did not find significant differences in the genotype distributions or allelic frequencies in the TPH1 218 A/C and TPH2 703G/T polymorphisms between the psychotic mania group and non-psychotic mania group.

Conclusion

We failed to found the statistically significant association between three polymorphisms and bipolar disorder. However, there was a trend towards association between 5-HT2A -1438A/G polymorphism and psychotic symptom in bipolar disorder. Future research should seek to clarify this association.     

Association of the T102C polymorphism of 5-HT2A receptor gene with aura in migraine

OBJECTIVE: To find out the significance of the 5-HT2A receptor gene polymorphism in migraine. Study design: A PCR study in which 61 migraineurs and 44 healthy controls were included. METHODS: The T102C polymorphism of the 5-HT2A receptor gene was studied. The results of the migraineurs and controls were compared. The relationship between the gene polymorphism and aura was also assessed. RESULTS: The representations of the 5-HT2A genotypes were similar in migraineurs and controls (p>0.05) as well as in the male and female migraineurs (p>0.05). The family history of migraine did not associate with 5-HT2A receptor gene polymorphism (p>0.05). There was a significant relationship between the presence of C/C genotype and migraine with aura (p=0.02) while C/T and T/T genotypes were over represented in the patients with migraine without aura (p<0.01). CONCLUSION: The T102C polymorphism of the 5-HT2A receptor gene is not directly related to the increased risk of migraine. The associations between the genotypes of this gene and aura may suggest that 5-HT2A receptor gene polymorphism may be involved in determining the subtypes of or accompanying symptoms in the migraine disease.     

Association study of the A2M and LRP1 Genes with Alzheimer disease in the Han Chinese.

BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) and alpha-2-macroglobulin (A2M) are two plausible candidate genes for Alzheimer disease (AD) based on their important biological function and positional information. To date, numerous studies have investigated their possible association with AD but the results are controversial. METHODS: To investigate the potential genetic contribution of the two genes in the Han Chinese population, we performed a case-control association study using 10 polymorphisms (4 in LRP1 and 6 in A2M) that span approximately the whole corresponding gene. RESULTS: Comparison of allele, genotype, and haplotype frequencies for polymorphisms in A2M revealed no significant differences between patients and control subjects. For the LRP1 gene, however, we found an overrepresentation of the CTCG haplotype in the control group (p = .002). The difference was still of statistical significance in the apolipoprotein E (APOE) epsilon 4 negative subjects (p(CTCG) = .003). Multiple logistic regression analysis did not show any evidence of synergism between A2M, LRP1, and APOE. CONCLUSIONS: Our results indicate that the CTCG haplotype of LRP1 may reduce the risk of late-onset AD, but A2M is not associated with this disease in the Han Chinese population.     

Reduced serotonin 5-HT1A receptor binding in the temporal cortex correlates with aggressive behavior in Alzheimer disease

Previous studies have implicated brain serotonin 5-HT(1A) receptors in several CNS functions, including cognition, mood and emotional states. In Alzheimer disease (AD), cognitive impairment and behavioral symptoms are the main clinical features. However, the biochemical basis of such changes is poorly understood. Results from recent in vivo studies suggest that 5-HT(1A) receptors may be related to aggressive traits in healthy subjects. The present study investigated the state of 5-HT(1A) receptors in the postmortem neocortex of 33 AD patients prospectively assessed for cognition and behavioral symptoms, together with 20 matched controls, by saturation [(3)H]8-OH-DPAT binding assays. 5-HT(1A) receptor binding affinity (K(D)) and density (B(max)) were unchanged in the overall AD group compared with controls. Within the AD group, 5-HT(1A) receptor B(max) in the temporal cortex inversely correlated with aggression and dementia severity. However, multiple regression analyses showed that 5-HT(1A) receptor B(max) remained the best predictor for aggression, while temporal cortical neurofibrillary tangle grading was the best predictor for dementia severity. This suggests that 5-HT(1A) receptor alteration is directly related to aggression in AD, while dementia severity is more strongly related to the neurodegenerative process. Our data indicate further study of 5-HT(1A) receptors as a pharmacological target for the treatment of behavioral symptoms in AD.     

Association analysis of the 5-HT6 receptor polymorphism C267T with depression in patients with Alzheimer's disease

A significant increase of 267C allele of the 5-HT(6) receptor gene has been reported in patients with Alzheimer's disease (AD). Because a deficit in serotonergic neurotransmission is involved in major depression, we tried to find out whether 267C allele is associated with depressive disorders in AD. A psychiatrist interviewed all AD patients and their caregivers for evidence of depression using a Chinese version of the Standard Clinical Interview for DSM-III-R. The difference in the 5-HT(6) genotype or allele distributions between the AD patients with depressive disorders (n = 25) and those without (n = 120) was not significant.     

精神分裂症与5-羟色胺受体2A多态性相关性研究

目的 探测精神分裂症与5-HT2A受体基因多态性关系。方法用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术分析90例精神分裂症患者的5-HT2A受体（T102C）基因多态性，并以90例正常人作为对照。结果 在精神分裂症组和正常对照组中，等住基因A1、A2及基因型A1／A1、A1／A2、A2／A2的差异没有显著性（P〉0．05）。结论 本组样本中5-HT2A受体（T102C）基因多态性与精神分裂症无相关性。提示5-HT2A受体基因（T102C）突变可能不是导致精神分裂症发病的主要因素。