The Relation of the Dopamine Transporter Gene (DAT1) to Symptoms of Internalizing Disorders in Children

The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders, Tourette's disorder, and obsessive-compulsive disorder was examined using both within- and between-family tests of association. The sample consisted of clinic-referred children and their siblings and controls and their siblings. Between-family association was examined via the association of DAT1 genotypes with disorder symptoms in the population. Symptoms of all eight disorders increased with a greater number of 10-repeat DAT1 alleles. Using a quantitative transmission disequilibrium test (QTDT), linkage and within-family association was indicated by increased symptoms in children who received 10 repeat alleles from heterozygous parents relative to children who received 9 repeat alleles. Four disorders were associated with DAT1 using the QTDT: generalized anxiety, social phobia, obsessive-compulsive, and Tourette's. The effects of comorbidity were investigated by repeating the same between- and within-family analyses on residual scores, with any effects of attention deficit hyperactivity disorder symptoms removed. Although the residuals were associated less strongly with DAT1 than were the original scores, three disorders continued to show association both between and within families: generalized anxiety, Tourette's, and social phobia.     

5-羟色胺转运体基因多态性与焦虑相关人格特质

5-羟色胺转运体（5-HTT）基因是个体间人格遗传差异和易发生多种精神障碍的一个最有前景的候选基因。该基因多态性通过影响基因转录而影响其功能,参与焦虑相关人格特质的调节。本文就 5-HTT基因与焦虑相关人格特质的关系及其研究进展作一综述。     

5-羟色胺转运体基因多态性与抑郁的关系研究进展

抑郁症作为一种复杂的情感性精神障碍,其病因及病理机制至今尚未完全阐明。5-羟色胺(5-HT)系统可能在抑郁的起病及发展中起重要作用,许多研究者在探索5-羟色胺转运体基因启动子区域连锁多态性(5-HTTLPR)与抑郁的关系上作了大量工作,已有许多研究成果出现,本文对以往的相关研究做一个综述。     

Association of Regulatory and Adaptive Status in Humans with Serotonergic Transmitter System Gene Polymorphism

Bulletin of Experimental Biology and Medicine - The regulatory and adaptive status was determined in 202 healthy subjects by the parameters of the cardiorespiratory synchronism probe. We performed...     

Gender Effects on Association of Serotonin Transporter Gene Polymorphism with Symptoms of Central Fatigue

In order to test the “serotonin” hypothesis of the genesis of central fatigue, we studied association between genotype and fatigue (3-hour mental workload consisting of information processing and logical task solution) using analysis of variance for different indices (well-being, activity, mood, mental fatigue index). It was concluded that young men with serotonin deficit (LL genotype) and girls with serotonin excess (S genotype) were less tolerant to long-lasting mental workload. Thus, we confirmed that the degree of central fatigue depends on the function of the serotonin system and revealed gender differences in adaptive capacities of carriers of different variants of serotonin transporter.     

Individual Differences in the Cardiac Response to High Intensity Auditory Stimulation

A recently reported long latency cardiac acceleration to the initial presentation of a high intensity white noise stimulus was investigated further with pure tones. In three experiments (involving 128 subjects) marked individual differences in the secondary response were uncovered. Many subjects not showing acceleration exhibited a secondary deceleration. Subjects were categorised into Accelerators, Decelerators, and a non-consistent-change group on the basis of cardiac activity in a 17-50 s poststimulus epoch. While both Accelerators and Decelerators exhibited short latency cardiac acceleration, it was of greater magnitude in the former. The long latency response is discussed with reference to a distinction between the defensive reflex and the fight/flight response. Discussion of the short latency response focuses on the startle reflex and the‘What's-to-be-done?’component of the response to a novel stimulus.     

XRCC1基因多态性影响奥沙利铂对晚期胃癌患者化疗疗效敏感性的关系

目的:研究DNA修复酶X射线损伤交叉互补蛋白1(X-ray repair cross-complementary protein 1,XRCC1)基因Arg399Gln多态性与晚期胃癌对奥沙利铂化疗敏感性的关系.方法:确诊的晚期胃癌患者68例,接受以奥沙利铂为主的化疗方案化疗.采用PCR-连接酶反应技术检测XRCC1 Arg399Gln多态性.比较不同基因型患者与化疗疗效及疾病进展时间(TTP)的关系.结果:68例胃癌患者中,38例(55.9%)携带XRCC 1 399Arg/Arg基因型,24例(35.3%)携带Arg/Gln基因型,6例(8.8%)携带Gln/Gln基因型.68例病人化疗总有效率(CR+PR)为48.5%(33/68),其中Arg/Arg基因型患者化疗有效率显著高于Arg/Gln+Gln/Gln基因型患者(60.5% vs 33.3%,χ2=4.963,P=0.026).68例患者中位TTP为8.0个月,其中Arg/Arg基因型患者为10个月,Arg/Gln+Gln/Gln基因型患者7.5个月,两者比较差异有显著性(χ2=17.383,P＜0.001).结论:XRCC1 Arg399Gln基因可以在一定程度上判断晚期胃癌患者接受奥沙利铂化疗后的预后情况.     

早老素1基因多态性与Alzheimer病的相关研究

目的探讨中国人群中早老素１（ＰＳ１）基因多态性与Ａｌｚｈｅｉｍｅｒ病（ＡＤ）的相关情况。方法应用聚合酶链式反应（ＰＣＲ）和限制性片段长度多态性（ＲＦＬＰ）方法,观察了５８例早发性ＡＤ患者、６５例迟发ＡＤ患者、１５７名正常人中的ＰＳ１多态性分布,并对ＡＤ与ＰＳ１基因的各等位基因和基因型进行关联分析。结果（１）早发ＡＤ患者中,ＰＳ１基因２／２型频率显著降低（Ｐ＜０．０５）;等位基因１频率显著升高,等位基因２频率显著降低（Ｐ＜０．０５）。迟发ＡＤ患者与正常对照之间不存在ＰＳ１等位基因和基因型分布的差异。（２）早发ＡＤ与ＰＳ１等位基因１正关联（ＲＲ＝２．２９,Ｐ＜０．０５）,与等位基因２（ＲＲ＝０．４４）和２／２基因型负关联（ＲＲ＝０．２３,Ｐ＜０．０５）;迟发ＡＤ与ＰＳ１各等位基因及等位基因型之间无明显关联。（３）ＡｐｏＥε４型、早发性及女性ＡＤ患者与ＰＳ１基因的相关性尤为显著。结论中国人群中ＰＳ１基因多态性可能仅与早发ＡＤ之间具有关联,而与迟发ＡＤ无关;这种关联具有年龄、性别差别     

Expression of Serotonin Transporter Gene and Startle Response in Rats with Genetically Determined Fear-Induced Aggression

The study was carried out on Norway rats selected through more than 60 generations for high and low fear-induced aggressiveness towards humans (Institute of Cytology and Genetics). The intensity of aggressive behavior towards man, reflex startle response, and expression of serotonin transporter (5-HTT) gene were studied. Selection for high aggression was associated with more intense startle response. The expression of 5-HTT gene in the frontal cortex was reduced significantly in rats selected for high aggression to humans in comparison with nonaggressive rats. The authors conclude that 5-HTT is involved in the regulation of genetically determined fear-induced aggression. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 147, No. 1, pp. 86-89, January, 2009     

Intraskeletal Variability of Relative Cortical Area in Humans

Histomorphometric and cross‐sectional geometric studies of bone have provided valuable information about age at death, behavioral and activity patterns, and pathological conditions for past and present human populations. While a considerable amount of exploratory and applied research has been completed using histomorphometric and cross‐sectional geometric properties, the effects of intraskeletal variability on interpreting observed histomorphometric data have not been fully explored. The purpose of this study is to quantify intraskeletal variability in the relative cortical area of long bones and ribs from modern humans. To examine intraskeletal variability, cross‐sections of the femur, tibia, fibula, humerus, radius, ulna, and rib when present, were examined within individuals from a cadaveric collection (N = 34). Relative cortical area was compared within individuals using a repeated measurements General Linear Model, which shows significant differences between bones, particularly between the rib and the remaining long bones. Complementarily, correlations between bones’ relative cortical area values suggest an important allometric component affecting this aspect of long bones, but not of the rib. This study highlights the magnitude of intraskeletal variability in relative cortical area in the human skeleton, and because the relative cortical area of any particular bone is affected by a series of confounding factors, extrapolation of relative cortical area values to infer load history for other skeletal elements can be misleading. Anat Rec, 298:1635–1643, 2015. © 2015 Wiley Periodicals, Inc.     

Association of 5-HTTLPR Serotonin Transporter Gene Polymorphism and Val66Met Brain-Derived Neurotrophic Factor Gene Polymorphism with Auditory N100 Evoked Potential Amplitude in Patients with Endogenous Psychoses

We studied the relationship between genes of serotonin transporter and brain-derived neurotrophic factor and parameters of AEP N100 wave to a non-significant stimulus in patients with endogenous mental diseases. In patients with endogenous psychoses, a significant effect of BDNF Val66Met marker on N100 wave amplitude was revealed: the mean N100 amplitude was higher in carriers of Val/Val genotype compared to Val/Met genotype carriers. The effect of the 5-HTTLPR marker on the wave amplitude was less pronounced (tendency): the SS genotype was associated with higher N100 amplitude. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 11, pp. 541–544, November, 2008     

Association of Serotonin Transporter Promoter Gene Polymorphism (5-HTTLPR) With Depression in Costa Rican Schizophrenic Patients

Abstract:

Depression and suicidal behavior are frequently observed in patients with schizophrenia. The serotonin transporter protein regulates serotonergic signaling at synapses and is encoded by a single gene (SLC6A4; Locus Link ID: 6532), located at 17q11.1-q12 with two polymorphic variants (the short and the long allele). The short allele of serotonin transporter gene has been associated with depression and suicidality in individuals who suffered negative life events and with depression in individuals with chronic psychosis.. Subjects were recruited from a genetic study of schizophrenia conducted in Costa Rica. The authors replicated their previous research, using a more narrow phenotype (only schizophrenic subjects) and a more ethnically homogenous sample (only Costa Rican schizophrenic individuals who were not included in the previous study). The authors hypothesized that subjects with at least one copy of the serotonin transporter promoter gene polymorphism (5-HTTLPR) “s” allele would have a greater history of lifetime depression and suicidability rate than those who had an “l/l” genotype. The authors analyzed 155 subjects with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia (73% male, age at interview 38.3, SD = 11.23). The genotype distribution was “ss” 58 (37%), “sl” 69 (45%), and “ll” 28 (18%). In the secondary analysis, the authors explored association of the “s” allele with lifetime history of suicide behavior in 173 subjects (18 more subjects than primary analysis because schizophrenic individuals were included regardless of history of depression). The authors found that subjects carrying at least one short allele had a significant increased lifetime risk for depressive syndromes (χ² = 5.4, df = 1, P = 0.02; odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.15–6.3). No association was found for suicidal behavior in the same sample (χ² = 0.928, P = 0.629). In conclusion, the genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of developing major depression but not suicidal behavior during the course of the schizophrenia in these patients. Due to the small sample size, these results should be followed by definitive replication.     

Baroreflex-Mediated Changes in Cardiac Output and Vascular Conductance in Response to Alterations in Carotid Sinus Pressure during Exercise in Humans

We sought to quantify the contribution of cardiac output ( Q ) and total vascular conductance (TVC) to carotid baroreflex (CBR)-mediated changes in mean arterial pressure (MAP) during mild to heavy exercise. CBR function was determined in eight subjects (25 ± 1 years) at rest and during three cycle exercise trials at heart rates (HRs) of 90, 120 and 150 beats min⁻¹ performed in random order. Acute changes in carotid sinus transmural pressure were evoked using 5 s pulses of neck pressure (NP) and neck suction (NS) from +40 to −80 Torr (+5.33 to −10.67 kPa). Beat-to-beat changes in HR and MAP were recorded throughout. In addition, stroke volume (SV) was estimated using the Modelflow method, which incorporates a non-linear, three-element model of the aortic input impedance to compute an aortic flow waveform from the arterial pressure wave. The application of NP and NS did not cause any significant changes in SV either at rest or during exercise. Thus, CBR-mediated alterations in Q were solely due to reflex changes in HR. In fact, a decrease in the carotid-HR response range from 26 ± 7 beats min⁻¹ at rest to 7 ± 1 beats min⁻¹ during heavy exercise (   P = 0.001  ) reduced the contribution of Q to the CBR-mediated change in MAP. More importantly, at the time of the peak MAP response, the contribution of TVC to the CBR-mediated change in MAP was increased from 74 ± 14 % at rest to 118 ± 6 % (   P = 0.017  ) during heavy exercise. Collectively, these findings indicate that alterations in vasomotion are the primary means by which the CBR regulates blood pressure during mild to heavy exercise.     

Functional Variability of Rev Response Element in HIV-1 Primary Isolates

We have previously studied sequence heterogeneity of HIV-1 Rev response element (RRE), and showed uneven variations in different stem–loops of both primary sequence and secondary structure. Here we studied the functional variation of RRE clones from a set of 10 primary isolates, and demonstrated a variation in the function of these RRE clones on the expression of Gag proteins from a truncated HIV-1 genome. The difference in Gag level was, in part, if not exclusively, resulted from the differential efficiency of RNA transport and enhancing of translation. These data suggested that variation of HIV-1 RRE may play a role in regulation of viral replication rate in HIV-1 primary isolates.     

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism,Anxiety and Depression

We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression. Edited by Stacey Cherny     

Genetic Polymorphism in the Serotonin Transporter Promoter Region and Ecological Success in Macaques

A well-characterised sequence length polymorphism in the serotonin transporter promoter region (5-HTTLPR) influences individual behavioural traits and cognitive abilities in humans and rhesus macaques. Macaques have been classified into four continuous grades on the basis of their behavioural attributes, ranging from highly hierarchical and nepotistic species to the most egalitarian and tolerant ones. A comparative study of several species that spanned these grades revealed only rhesus macaques to be polymorphic at the 5-HTTLPR and concluded that the polymorphism was responsible for their despotic and aggressive behaviour (Wendland et al., Behav Genet 36:163–172, 2006). We studied wild populations of three other species and found that the egalitarian and tolerant bonnet and Arunachal macaques are also polymorphic while liontailed macaques, although belonging to the same group, are monomorphic. We thus reject a role for this particular polymorphism in interspecific behavioural variability and show that polymorphic species enjoy greater ecological success possibly due to their higher intraspecific variability in individual behavioural traits.