5-羟色胺转运体启动子区域基因多态性位点与双相障碍的关联研究

目的:探讨5-羟色胺转运体蛋白基因启动子区域(5-HTTLPR)位点多态性与双相障碍之间的遗传学联系。方法:以中国西北地区汉族人群中51例双相障碍患者(患者组)的核心家系(父母组102名)共153人为研究对象;取每个成员血液样本DNA,应用聚合酶链反应技术扩增5-HTTLPR位点,以琼脂糖凝胶电泳法进行基因分型,对5-HTTLPR位点多态性与双相障碍之间分子遗传学联系进行以家系为基础的连锁不平衡分析。结果:无论5-HTTLPR位点各种基因型(L/L、L/LG、S/L、S/S、S/LG)还是等位基因(L、LG、S)频率在患者组和父母组比较差异无统计学意义(χ2=3.732,P0.05;χ2=0.633,P0.05)。基于基因型的单倍体相对风险分析(GHRR)以及传递不平衡分析(TDT)也未发现5-HTTLPR与双相障碍存在连锁不平衡(GHRR:P0.05;TDT:χ2=2.418,P0.05)。结论:5-HTTLPR多态性位点在中国西北地区汉族人群双相障碍发病机制中不起主要作用,但不能排除微效作用的存在。     

5-羟色胺转运体基因多态性与氟西汀疗效及副反应的关系

目的探讨重性抑郁障碍(MDD)氟西汀疗效及不良反应与5-羟色胺转运体启动子区基因多态性(5-HTTLPR)的关系。方法选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)重性抑郁障碍诊断标准的89例患者为研究对象。给予氟西汀治疗6周。利用聚合酶链反应(PCR)多态性技术检测5-HTTLPR多态性。结果不同基因型患者组之间治疗后HAMD总分减分率的差异有统计学意义(P<0.005),L/L基因型组的减分率高于另两种基因型组;有效组和无效组之间、有无恶心不良反应组之间的5-HTTL-PR的基因型和等位基因频率的差异均有统计学意义(P<0.05),L/L基因型组的疗效和恶心发生率高于另2组。结论5-HTTLPR基因多态性可能与氟西汀抗抑郁疗效及其恶心不良反应相关。     

5-羟色胺转运体基因功能性多态与强迫症的关联研究

目的 探讨中国汉族人群中5-羟色胺转运体基因启动子区域多态(5-HTTLPR)功能性3等位基因L_A、L_G和S与强迫症(OCD)的关系.方法 采用聚合酶链反应-限制性片段长度多态技术测定138例OCD患者(OCD组)和199名健康人(对照组)的5-HTTLPR功能性3等位基因多态性.结果 OCD组5-HTTLPR功能性基因型及等位基因频率与对照组间的差异有统计学意义(χ~2=8.396,P＜0.05;χ~2=8.483,P＜0.01);L_A/L_A因型和L_A等位基因与OCD存在显著正关联[比值比分别为3.361(P＜0.05)和1.771(P＜0.01)].结论在中国汉族人群中5-HTTLPR功能性3等位基因可能与OCD存在遗传关联,L_A/L_A基因型和等位基因L_A可能是OCD的风险因子.     

Association of serotonin transporter gene polymorphisms and major depressive disorder in Chinese Han population

BACKGROUND： Serotonin transporter （5-HTT） polymorphisms comprise 5-HTT gene-linked polymorphism region （5-HTTLPR） and variable number of tandem repeats （VNTR）. Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the ＂S＂ allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE： To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING： Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS： A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale （24 items） ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS： Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES： 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS： No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls （P 〉 0.05）. However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected （P 〈 0.01 ）. The Stin2.10 allele and 10/10 genotype associated with major depressive disorder （OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01）. CONCLUSION： Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.     

双相障碍患者5-HTTLPR基因多态性与认知诱发电位的相关性

目的 探讨双相障碍患者的5-羟色胺转运体基因启动子区（5-HTTLPR）基因多态性分布 特征和认知功能损害的特点。方法 运用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）技术 测定100 例双相障碍患者（研究组）和100 名健康对照者（对照组）的5-HTTLPR基因多态性。运用事件 相关电位对所有被试者进行认知功能评定。运用HAMD（24 项版本）、Bech-Rafaelsen 躁狂量表（BRMS） 分别评定双相障碍患者抑郁相、躁狂相的严重程度。结果 两组5-HTTLPR 基因型频率和等位基因 频率差异均无统计学意义（P＞ 0.05）；双相障碍患者躁狂相BRMS 评分与事件相关电位P3 潜伏期呈正 相关（r=0.321，P＜ 0.01），而抑郁相HAMD 评分与事件相关电位N1、P2、N2、P3 潜伏期及波幅呈正相关 （r=0.637、0.379、0.472、0.572、0.433，P＜ 0.05）；双相障碍患者中携带LL基因型较SS 基因型更容易患躁 狂相（OR=2.471，P＜ 0.05）；无序多分类Logistic 回归模型综合分析，只有躁狂相P3 波幅进入回归方程 （P=0.033），余变量均未进入。结论 5-HTTLPR 基因多态性与双相障碍的发病及事件相关电位无相关 性，双相障碍患者均存在认知功能损害，其中抑郁相认知功能损害较为显著，双相障碍患者中携带LL 基因型较SS 基因型可能更容易患躁狂相。     

伴发睡眠障碍首发抑郁症认知功能损害及影响因素分析

目的探讨伴发睡眠障碍首发抑郁症患者的认知功能损害特点及其影响因素。方法纳入318例首发抑郁症患者,根据睡眠情况分为伴发睡眠障碍组(202例)和不伴发睡眠障碍组(116例),并纳入243名正常对照。采用重复性成套神经心理状态测验(repeatable battery for the assessment of neuropsychological status,RBANS)评估所有被试的认知功能(即刻记忆、视觉广度、言语功能、注意、延迟记忆),并采用17项汉密尔顿抑郁量表(Hamilton depression rating scale,HAMD-17)评估患者的抑郁症状。结果伴发睡眠障碍组即刻记忆、视觉广度、言语功能、延时记忆得分及量表总分均比不伴发睡眠障碍组及对照组差(均P<0.05);而不伴发睡眠障碍组的即刻记忆、言语功能、延时记忆得分及量表总分比对照组差(均P<0.05)。多因素线性回归分析示,伴发睡眠障碍组中,RBANS量表总分与HAMD认知障碍因子相关联(β=6.29,P=0.04),即刻记忆得分与年龄相关联(β=-0.24,P=0.04),视觉广度得分与HAMD睡眠变化因子相关联(β=2.33,P=0.01),言语功能得分与婚姻(β=-5.74,P=0.01)及HAMD阻滞因子(β=-1.20,P=0.03)相关联;不伴发睡眠障碍组中,RBANS的言语功能得分与年龄相关联(β=-0.32,P=0.04),注意得分与HAMD阻滞因子相关联(β=2.52,P=0.01)。结论伴发睡眠障碍组患者存在多方面的认知功能损害,抑郁相关症状(睡眠变化、认知障碍、阻滞等)、年龄及婚姻状况可能是伴发睡眠障碍抑郁患者认知功能损害的影响因素。     

原发性失眠的5-羟色胺转运体基因遗传多态性研究

目的　探讨原发性失眠与羟色胺转运体( 5 -HTT)基因遗传多态性的关系。方法　对85例病例组和54名对照组提取外周血基因组DNA ,进行PCR扩增,分析相应的基因型,并比较两组不同基因型患者的焦虑和抑郁评分有无差异。结果　两组的5 -HTTLPR和5 -HTTVNTR的基因型、等位基因频率及不同基因型频率的两两比较均无显著性差异(P >0 .0 5) ;病例组5- HTTLPR的S/S(S组)和S/L +L/L(L组)两组之间及5- HTTVNTR的1 0 / 1 0 + 1 0 / 1 2 ( 1 0组)和1 2 / 1 2 ( 1 2组)两组之间的焦虑、抑郁量表评分比较均无显著性差异(P >0 . 0 5)。结论　5- HTTLPR和5 -HTTVNTR两种基因遗传多态性与原发性失眠的关系尚需进一步探讨。     

5-羟色胺转运体基因多态性与脑卒中后抑郁的关系

目的 探讨5-羟色胺转运体基因启动子区域多态性(5-HTTLPR)与中国汉族人群脑卒中后抑郁(PSD)的关系.方法 应用PCR技术,比较96例PSD、97例脑卒中后非PSD及60名健康对照组上述位点基因型及等位基因频率.结果 PSD组5-HTTLPR多态的S/S基因型频率和S等位基因频率显著高于脑卒中非PSD组和健康对照组(均P＜0.05),S等位基因与PSD呈正关联(比值比OR=1.76,P＜0.01,95％CI:1.15～2.69).结论 5-HTTLPR S/S基因型和S等位基因可能为脑卒中后抑郁的易患因素.     

5-羟色胺转运体基因多态性与自杀未遂的关联研究

目的探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与自杀未遂的关系。方法运用聚合酶链反应技术(PCR)检测71例自杀未遂患者和80名健康对照5-HTTLPR基因型。结果自杀未遂组与对照组5-HTTLPR的基因型及等位基因(S/L)频率差异无统计学意义(P>0.05);进一步分析显示,有精神疾病自杀未遂组(37例)的短重复序列S等位基因频率为85.1%,与正常对照组(72.5%)及无精神疾病自杀未遂组(69.1%)的差异均具有统计学意义(X2=4.49,P=0.04;X2=5.21,P=0.03)。结论5-HTTLPR的S等位基因和精神病自杀未遂存在关联。     

同型半胱氨酸及其代谢关键酶MTHFR基因C677T多态性与重性抑郁症的相关研究

目的 探讨血浆同型半胱氰酸(Hcy)水平及5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性与重性抑郁症(MDD)的关系.方法 纳入符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)MDD诊断标准的患者77例和正常对照85名,采用荧光偏振免疫法测定Hcy浓度,运用聚合酶链反应-限制性内切酶片段长度多态性分析技术(PCR-RFLP)检测MTHFR基因C677T多态性.入组时对MDD忠者进行汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评定.结果 患者组血浆Hcy水平明显高于对照组,差异有统计学意义(P<0.05).患者组与对照组基因型频率和等位基因频率分布差异有统计学意义(P<0.05).患者组和对照组TT基因型Hcy浓度均较CT型、CC型高.且患者组TT型HAMD评分也比后两者高(P<0.05).多元线性同归分析结果显示,MDD患者血浆Hcy水平与年龄、HAMD评分和TT基因型有关(P<0.001).结论 MTHFR基因C677T多态性可能是MDD的遗传易感因素,其可能通过影响血清Hcy水平而参与了MDD的发病及临床表现.     

抑郁症还是双相障碍？

1 病史简介 患者,男,34岁,工人,已婚。因反复烦躁不安、情绪低落发作19年,于2011年5月26日第1次住我院。患者于1992年读初中二年级时与同学打架后,对老师的处理方式不满,渐出现不愿意读书,眠差,情绪不稳定,烦躁,之后出现情绪低落,注意力不易集中,记忆力下降,兴趣减退,自1992年起休学。     

双相障碍与强迫症的共病

概述

在双相障碍患者中强迫症状是常见的。因为双相障碍和强迫症的共病状态会令这两种障碍的临床治疗复杂化，所以确定这些共病的患者是很重要的。我们讨论了强迫症和双相障碍的共病，介绍了可能导致这种常见共病状态的发病机制，也讨论了该领域最新的研究进展，并提出一些管理这些患者的临床原则。

中文全文

本文全文中文版从2015年10月26日起在http://dx.doi.org/10.11919/j.issn.1002-0829.215009可供免费阅览下载 Previous studies have documented high rates of comorbidity of other psychiatric conditions among individuals with bipolar disorders (BD).[1] One study estimated that obsessive-compulsive disorders (OCD) accounted for 21% of all comorbidities in BD.[2] There is continuing debate about whether (a) these are two independent conditions that can co-occur or (b) OCD is a specific subtype of BD. Regardless of the interrelationship of the two conditions, the comorbid occurrence of these two types of symptoms can cause a clinical dilemma because selective serotonin reuptake inhibitors (SSRIs)-which are quite commonly used to treat OCD-increases the risk of precipitating manic symptoms.[3,4,5,6] The OCD symptoms that occur in individuals with BD often occur during the depressive episodes or during the intervals between episodes of depressive or manic symptoms.[7,8] This timing of OCD symptoms during BD is consistent with the cyclic nature of BD and suggests shared biological mechanisms between the two disorders. In support of this hypothesis, a study using Positron Emission Tomography (PET) found that in untreated persons with BD the serotonin-transporter binding potential in the insular and dorsal cingulate cortex was higher among BD patients with pathological obsessions and compulsions than among BD patients without such symptoms.[9] Moreover, a linkage study found that compared to OCD patients without comorbid BD, patients with comorbid OCD and BD were more likely to have a family history of mood disorders but less likely to have a family history of OCD.[10] However, another study found no significant difference in the rates of a positive family history of OCD between patients with OCD alone and those with comorbid OCD and BD.[11] Further support for the hypothesized common etiology comes from a preliminary molecular genetic study which found that hyperpolarization activated cyclic nucleotide-gated channel 4 (HCN4) is a common susceptible locus for both mood disorders and OCD, but further studies with larger sample sizes are needed to replicate this finding.[12] The presence of OCD in BD complicates the clinical presentation. Compared to patients with BD without comorbid OCD, those that have comorbid BD and OCD often have a more severe form of BD, have more prolonged episodes, are less adherent to medication, and are less responsive to medication. Recent studies about comorbid BD and OCD have reported the following: (a) Temporal relationship. Some studies suggest that OCD is an antecedent of BD,[10] but others report concurrent onset of OCD and BD.[13,14] (b) Course of disease. In 44% of patients with comorbid BD and OCD the episodes are cyclic.[15] The course of disease is more chronic among BD patients with OCD compared to those without comorbid OCD.[16,17] OCD is more commonly observed in patients with Type II BD, among whom the prevalence of OCD has been reported to be as high as 75%.[18] (c) Compulsive behaviors. The most commonly reported compulsions among patients with comorbid OCD and BD are compulsive sorting,[14,19,20,21] controlling or checking, [20] repeating behaviors,[13,22] excessive washing,[20] and counting.[19] Obsessive reassurance-seeking is also commonly reported in these patients.[23] In children and adolescents with BD, compulsive hoarding, impulsiveness,[24] and sorting[25] are more common. (d) Substance and alcohol abuse. A study found a higher prevalence of sedative, nicotine, alcohol, and caffeine use among individuals with comorbid OCD and BD compared to those with BD without OCD.[14] Similarly, compared to OCD patients without comorbid mood disorders, those with a comorbid mood disorder were more likely to have a substance abuse diagnosis (OR=3.18, 95%CI=1.81-5.58) or alcohol abuse diagnosis (OR=2.21, 95%CI=1.34-3.65).[11,13,26,27,28] (e) Suicidal behaviors. Compared to BD patients without OCD, a greater proportion of patients with both disorders had a lifetime history of suicidal ideation and suicide attempts.[2,11,13,29,30] The clinical management of comorbid OCD and BD requires first focusing on stabilizing the patient’s mood, which requires the combined use of multiple medications such as the use of lithium with anticonvulsants or atypical antipsychotic medications such as quetiapine;[31,32,33] adjunctive treatment with aripiprazole may be effective for the comorbid OCD symptoms.[4] In the case of OCD comorbid with type II BD, after full treatment of the mood symptoms with mood stabilizers the clinician can, while monitoring for potential drug interactions, cautiously try adjunctive treatment with antidepressants that are effective for both depressive symptoms and OCD symptoms and that have a low risk of inducing a full manic episode, including the selective serotonin reuptake inhibitors (SSRIs): fluoxetine, fluvoxamine, paroxetine, and sertraline.[32,35] In summary, BD comorbid with OCD may be etiologically distinct from either of the disorders. Clinicians should pay attention to its complex clinical manifestations and carefully consider the treatment principles outlined above.     

Posttraumatic stress disorder and substance use disorder in adolescent bipolar disorder

Objective: Anxiety disorders such as posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are increasingly recognized as comorbid disorders in children with bipolar disorder (BPD). This study explores the relationship between BPD, PTSD, and SUD in a cohort of BPD and non‐BPD adolescents. Methods: We studied 105 adolescents with BPD and 98 non‐mood‐disordered adolescent controls. Psychiatric assessments were made using the Kiddie Schedule for Affective Disorders and Schizophrenia–Epidemiologic Version (KSADS‐E), or Structured Clinical Interview for DSM‐IV (SCID) if 18 years or older. SUD was assessed by KSADS Substance Use module for subjects under 18 years, or SCID module for SUD if age 18 or older. Results: Nine (8%) BPD subjects endorsed PTSD and nine (8%) BPD subjects endorsed subthreshold PTSD compared to one (1%) control subject endorsing full PTSD and two (2%) controls endorsing subthreshold PTSD. Within BPD subjects endorsing PTSD, seven (39%) met criteria for SUD. Significantly more SUD was reported with full PTSD than with subthreshold PTSD (χ² = 5.58, p = 0.02) or no PTSD (χ² = 6.45, p = 0.01). Within SUD, the order of onset was BPD, PTSD, and SUD in three cases, while in two cases the order was PTSD, BPD, SUD. The remaining two cases experienced coincident onset of BPD and SUD, which then led to trauma, after which they developed PTSD and worsening SUD. Conclusion: An increased rate of PTSD was found in adolescents with BPD. Subjects with both PTSD and BPD developed significantly more subsequent SUD, with BPD, PTSD, then SUD being the most common order of onset. Follow‐up studies need to be conducted to elucidate the course and causal relationship of BPD, PTSD and SUD.     

Substance use disorder and personality disorder

Personality disorders (PDs) and substance use disorders (SUDs) frequently co-occur in both the general population and in clinical settings. Literature is reviewed documenting high comorbidity between these two classes of disorders, possible mechanisms of comorbidity, and the clinical implications of this comorbidity. Special emphasis is given to antisocial personality disorder (ASPD) and borderline personality disorder (BPD) as these disorders not only co-occur frequently with SUDs in the clinical populations and present clinical challenges, but also because recent research points to etiologic processes that are common to these specific PDs and SUDs. Although most attention on comorbidity between PDs and SUDs has focused on ASPD and BPD, it is also clear that other PDs (in particular, avoidant PD and paranoid PD) are prevalent among those suffering from SUDs.     

Thought disorder in attention-deficit hyperactivity disorder

OBJECTIVE: This study compared thought disorder and associated cognitive variables in attention-deficit hyperactivity disorder (ADHD) and schizophrenia. METHOD: Speech samples of 115 ADHD, 88 schizophrenic, and 190 normal children, aged 8 to 15 years, were coded for thought disorder. A structured psychiatric interview, the WISC-R, the Continuous Performance Test, and the Span of Apprehension task were administered to each child. RESULTS: The ADHD and schizophrenic groups had thought disorder compared with the normal children. However, the subjects with ADHD had a narrower range of less severe thought disorder than did the schizophrenic subjects. The younger children with ADHD and schizophrenia had significantly more thought disorder than did the older children with these diagnoses. IQ, attention, and working memory were associated with thought disorder in the ADHD but not the schizophrenic group. CONCLUSIONS: Thought disorder in childhood is not specific to schizophrenia and reflects impaired development of children's communication skills.