Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population

Background

Previous candidate gene studies of major depressive disorder (MDD) have provided inconclusive evidence of association for genes with strong biological rationale for MDD. In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population.

Methods

Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder were recruited for the study. 371 normal controls were recruited from local community. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants by polymerase chain reaction. Male and female subjects were analyzed separately.

Results

No differences were found in the frequencies of the single alleles and genotypes of the tested polymorphisms between MDD patients and normal group. The frequency of the A-A haplotype was significantly higher in female MDD compared to healthy female controls (P < 0.05). No significant association with treatment response was discovered in haplotype and single-marker analysis.

Limitations

This study lacks a placebo control and we cannot definitively exclude the possibility that some patients in the responder group responded to the placebo effect alone.

Conclusion

The result suggests that TPH2 gene may have a gender dependent effect on susceptibility to MDD but not with its treatment response in Chinese Han population. Further studies are needed to replicate the association that we observed.     

No Evidence of an Association between A218C Polymorphism of the Tryptophan Hydroxylase 1 Gene and Aggression in Schizophrenia in a Korean Population

Purpose

We investigated the association between the tryptohan hydroxylase 1 (TPH1) gene and aggression in schizophrenia in a Korean population.

Materials and Methods

The sample included 61 aggressive patients as well as 104 non-aggressive patients from psychiatric hospitals and 335 healthy volunteers in Korea. Blood samples were collected from all participants for TPH1 A218C genotyping. The patients were administered standard psychiatric interviews as well as a self-report questionnaire for anger-related traits.

Results

In the case-control phenotypic comparisons, there was no significant association between the aggressive patients and the TPH1 A218C polymorphism. There was no significant effect of the TPH1 genotype on the anger-related traits, or no significant interaction between the genotype and group (aggressive and non-aggressive patients).

Conclusion

These findings suggest that TPH1 does not play a major role in aggressive behavior via anger in schizophrenic patients.     

Association study of tryptophan hydroxylase 2 gene polymorphisms in panic disorder

Experimental studies on serotonin (5-HT) availability suggest a role for 5-HT synthesis rate in panicogenesis. Recently, it has been discovered that the tryptophan hydroxylase gene isoform 2 (TPH2), rather than TPH1, is preferentially expressed in the neuronal tissue and, therefore, is primarily responsible for the regulation of brain 5-HT synthesis. In the present case-control genetic association study we investigated whether panic disorder (PD) phenotypes are related to two single nucleotide polymorphisms (SNP) of TPH2, rs1386494 A/G and rs1386483 C/T. The study sample consisted of 213 (163 females and 50 males) PD patients with or without affective comorbidity and 303 (212 females and 91 males) matched healthy control subjects. The allelic and genotypic analyses in the total sample did not demonstrate significant association of PD with the studied SNPs, suggesting that these polymorphisms may not play a robust role in predisposition to PD. However, an association with rs1386494 SNP was observed in the subgroup of female patients with pure PD phenotype, indicating a possible gender-specific effect of TPH2 gene variants in PD.     

惊恐障碍患者血清VGF水平的对照研究

目的 探讨惊恐障碍患者血清VGF水平的变化,分析其与疾病临床症状的关系及其对惊恐障碍的辅助诊断价值。方法 选择东南大学附属中大医院心理精神科2015年4月~2016年8月住院的惊恐障碍患者30例作为研究对象,设为惊恐障碍组。另选同期东南大学附属中大医院体检中心的健康体检者30例设为对照组。采用酶联免疫吸附实验（ELISA）检测血清VGF蛋白水平,同时采用惊恐障碍严重程度量表（PDSS）、汉密尔顿焦虑量表（HARS）对所有研究对象进行评估;采用Spearman相关分析对血清VGF水平与焦虑评分、惊恐症状严重程度进行相关性分析,并使用受试者工作特征（ROC）曲线评价VGF辅助诊断惊恐障碍的价值。结果 惊恐障碍组血清VGF水平为（874.16±42.84）pg/ml,低于对照组的（1041.47±53.74）pg/ml,差异有统计学意义（P＜0.05）。相关分析未发现血清VGF水平与惊恐障碍的严重程度、HARS得分等临床变量之间存在相关性（P＞0.05）。ROC分析显示,血清VGF辅助诊断惊恐障碍的阈值（cut-off）为972.19 pg/ml,对应的ROC曲线下面积（AUC）为0.999,特异性为96.70%,敏感性达100.00%。结论 血清VGF水平在惊恐障碍患者中显著降低,具有辅助诊断惊恐障碍的价值。     

惊恐障碍的非精神科误诊调查分析

目的调查惊恐障碍患者的误诊特点。方法自制统计表对55例确诊惊恐障碍的患者的性别、年龄、疾病病程、曾误诊的疾病种类、重复就诊于非精神科次数、误诊期间诊治费用以及正确治疗后达临床治愈的疗程进行调查统计。结果 52.73%的惊恐障碍患者非精神科误诊时间长于1年;58.18%的患者就诊非精神科次数少于5次,14.55%的患者大于10次;误诊期间浪费的诊治费用有47.27%的患者超过5000元;确诊后住院治疗期90.91%的患者在2个月内惊恐发作消失。结论惊恐障碍的非精神科误诊率高,误诊时间长,医疗资源浪费严重,但确诊后经精神科治疗近期疗效较好。     

万拉法新治疗惊恐障碍疗效对比分析

目的　对比分析万拉法新治疗惊恐障碍的治疗效果。方法　随机设观察组 ( 2 2例 )和对照组 ( 2 0例 ) ,并对两组进行HAMA、CGI、TESS和国内统一 4级疗效评定和比较。结果　两组间 HAMA治疗前和治疗后 4周末均 P>0 .0 5 ;治疗后 1周末和 2周末均 P<0 .0 0 1 ;治疗后 4周末与治疗前两组 HAMA均降分明显 ,均 P<0 .0 0 1。两组间 SI、GI比较 ,均为 P>0 .0 5 ;EI比较 ,P<0 .0 5 ;TESS比较 ,P<0 .0 0 1。两组疗效构成比的比较 ,P>0 .0 5。结论　万拉法新具有快速、有效和药物副反应相对轻微的特点 ,治疗依从性较好 ,不失为治疗惊恐障碍的首选药物。     

认知行为疗法联合药物治疗惊恐障碍疗效Meta分析

目的:比较认知行为疗法(CBT)联合药物治疗与单纯药物治疗对惊恐障碍的疗效。方法:对CBT联合药物治疗与单纯药物治疗惊恐障碍的对照研究进行系统评价,使用Revman 5.2进行Meta分析。结果:共纳入6项符合标准的随机对照研究,合计样本量329人。6组数据比较了CBT联合药物治疗与单纯药物治疗惊恐障碍的有效率和显效率,结果显示,联合治疗组的有效率(OR=3.28,Z=2.75,P<0.05)与显效率(OR=2.85,Z=3.90,P<0.05)均优于单纯药物组;5组数据比较了CBT联合药物治疗与单纯药物治疗惊恐障碍的治愈率,结果显示,联合治疗组的治愈率优于单纯药物组(OR=2.08,Z=2.82,P<0.05)。结论:鉴于目前结果推测对于惊恐障碍的改善,认知行为疗法联合药物治疗优于单纯药物治疗,但仍需进一步研究证实。     

认知行为疗法并帕罗西汀治疗惊恐障碍疗效分析

目的评价认知行为疗法并帕罗西汀治疗惊恐障碍的治疗效果。方法将符合中国精神障碍分类与诊断标准的69例惊恐障碍患者随机分为研究组（n=37）和对照组（n=32）。研究组给予认知行为并帕罗西汀治疗,对照组单用帕罗西汀治疗,疗程12周,在入组前和治疗2、4、8、12周末应用临床疗效标准和汉密尔顿焦虑量表（HAMA）评定疗效。完成该研究的60名参与者的数据纳入了结果分析。结果汉密顿焦虑量表总分研究组治疗2周末较治疗前有极显著性下降（t=5.56,P〈0.01）;对照组治疗4周末较治疗前有极显著性下降（t=4.27,P〈0.01）;治疗后2、4、8、12周末研究组疗效显著优于对照组。结论认知行为疗法并帕罗西汀治疗惊恐障碍效果优于单用帕罗西汀治疗。     

1例初中生惊恐障碍的诊断与治疗

目的以1例惊恐障碍的初中生为例探讨条件性情绪干预法对惊恐障碍干预的有效性,为惊恐障碍的心理干预提供临床借鉴。方法在单个被试的情况下,采用多基线实验设计,运用条件性情绪干预法对来访者进行临床干预。同时用汉密顿焦虑量表（HAMA）、焦虑自评量表（SAS）、症状自评量表（SCL-90）对干预过程中各项指标的变化进行评估。结果干预后来访者的各项指标稳定,惊恐发作次数减少,焦虑水平降低,社会适应性增强。结论运用条件性情绪干预法可对惊恐障碍进行有效干预,降低惊恐焦虑水平,长期训练有彻底治愈的可能。     

TPH2基因单核苷酸多态性与双相情感障碍及其自杀行为的关系

目的 探讨色氨酸羟化酶2(TPH2)基因rs7305115单核苷酸多态性与双相情感障碍及自杀行为的关系.方法 提取205例双相情感障碍患者和225名健康对照者基因组DNA,采用聚合酶链反应(polymerase chain reaction PCR)扩增包括TPH2基因rs7305115位点的312bp基因组DNA片段,PCR产物直接测序.结果 在第7外显子周围未发现其它的单核苷酸多态性.双相情感障碍患者和健康对照者TPH2 rs7305115基因型和等位基因频率无统计学意义的差别(P>0.05),但患者组内有自杀行为的个体携带基因型AA的频率及等位基因A的频率均较低,两组比较差异有统计学意义(P<0.05).结论 TPH2基因rs7305115单核苷酸多态性与双相情感障碍无明显关联,与自杀行为有关联,其可能与双相情感障碍自杀行为易感性相关.

Abstract：

Objective To explore the relation among single nucleotide polymorphism of a novel tryptophan hydroxylase isoform (TPH2) gene rs7305115,bipolar disorder and suicidal behavior. Methods Specimens of peripheral blood were collected from 205 bipolar disorder and 225 controls. A novel tryptophan hydroxylase isoform (TPH2) gene rs7305115 in length 312bp was amplitied by Polvmerase chain reaction (PCR), and the product was analyzed by direct sequencing. Results We did not discover new single nucleotide polymorphism. Compared with Control Group,no significant difference of genotypes and alleles of TPH2 gene rs7305115 single nucleotide polymorphism had been found in patient group(P>0. 05). However,there existed significant differences between suicide behavior and non suicide behavior in bipolar disorder patient in genotypea of TPH2 gene rs7305115A/A. Suicide behavior of bipolar disorder patients in AA genotypes was much lower than non suicide behavior of bipolar disorder patients (P<0. 05). Con-clusion TPH2 gene rs7305115 single nucleotide polymorphism may have no association with the susceptibility of bipolar disorder, but associated with suicide behavior in bipolar disorder. A allele may be one of the risk factors for suicide behavior in bipolar disor-der.     

帕罗西汀合并认知行为疗法治疗惊恐障碍对照研究

目的观察帕罗西汀合并认知行为疗法对惊恐障碍的治疗效果。方法将符合ICD-10诊断标准的40例惊恐障碍患者分为治疗组和对照组,治疗组给予帕罗西汀30~40mg/d合并认知行为治疗,对照组只给予帕罗西汀30~40mg/d治疗,应用临床标准疗效及汉密尔顿焦虑量表（HAMA）、临床疗效总评量表（CGI-SI）及副反应量表（TESS）评定疗效和不良反应。观察12周。结果在治疗第4、8和12周末时,治疗组疗效均优于对照组,具有显著性统计学意义（P〈0.05）。两组不良反应轻微,无需处理。结论帕罗西汀合并认知行为疗法治疗惊恐障碍效果优于单纯用药物治疗。     

1例研究生惊恐障碍的元认知心理干预实验研究

目的探讨惊恐障碍的心理机制及其干预方法,为惊恐障碍的心理干预提供临床借鉴。方法采用单被试多基线实验设计,运用元认知心理干预技术对来访者进行临床干预。结果干预前来访者症状自评量表(SCL-90)所有因子均显示异常,其中抑郁3.38,焦虑3.30,敌对3.67,汉密尔顿焦虑量表(HAMA)得分为36分。干预结束后SCL-90各项因子分均达到正常水平,HAMA得分为6分,基线指标稳定,惊恐发作次数减少,焦虑水平降低,社会适应性增强。结论实验证明元认知心理干预技术是治疗惊恐障碍的有效心理干预方法,值得推广。     

河北省惊恐障碍患者的功能状况及治疗现状调查

目的了解河北省惊恐障碍患者的功能状况及接受治疗现状。方法采用多阶段、整群、分层随机抽样方法调查河北省18岁及以上人群共24000人,调查筛选工具采用改编后的一般健康问卷12项(GHQ-12),以《DSM-ⅠV-TR轴Ⅰ障碍定式临床检查》(SCⅠD-T/P)病人版为调查的诊断工具,采用功能大体评定量表(GAF)评价功能状况。结果河北省惊恐障碍患者工作能力、日常生活、精神状况、社会交往、自我料理等功能状况都受到不同程度的影响,尤其以精神状况、工作能力和日常生活方面明显,受中等程度以上影响的比例分别为90.9%、76.4%和67.3%,并且有34.5%的患者希望自己死了才好,12.7%的患者出现自杀或自伤观念。因心理或精神问题去看过病的患者只有7.3%,在未看过病的患者中只有3.6%的患者意识到看心理医生会有用或可能有用。结论惊恐障碍患者社会和生活功能明显受损,容易出现自杀观念及行为,甚至产生社会功能残疾,应引起临床医生的重视,基层医师在向他们保证其没有躯体疾病的同时,应劝其接受充分的药物和心理治疗,同时,要在普通人群中扩大宣传,普及有关知识。     

惊恐障碍患者非理性信念、应对方式及其与症状的关系

目的:探讨惊恐障碍患者非理性信念、应对方式特点及其与症状的关系。方法:采用非理性信念问卷、应对方式问卷测评40例惊恐障碍患者及40例正常对照,并对惊恐障碍患者进行惊恐障碍严重程度量表的测评。结果:①与正常对照组相比,患者的非理性信念水平明显偏高(P<0.01),在自责、求助、幻想、回避、合理化应对方式上得分较高(P<0.05);②多元逐步回归结果显示:疾病严重程度量表总分受幻想因子与求助因子影响,与幻想呈正相关(β=0.422,P<0.01),与求助呈负相关(β=-0.339,P<0.05)。结论:惊恐障碍患者具有概括化评论、低挫折耐受和绝对化要求的非理性信念,且多采用自责、求助、幻想、回避、合理化的应对策略;幻想、求助应对方式可预测惊恐障碍严重程度。     

帕罗西汀、阿普唑仑单一及早期联合使用治疗惊恐障碍的对照研究

目的比较帕罗西汀、阿普唑仑单一使用及早期联合使用治疗惊恐障碍急性期的临床疗效和安全性。方法将符合入组标准的90例惊恐障碍患者随机至为阿普唑仑组、帕罗西汀组和两药合用组各30例,为期12周。以临床判断和惊恐症状评定量表(PASS)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评定临床疗效,以副反应量表(TESS)评定药物不良反应。结果在治疗第1周末,阿普唑仑组及合用组PASS、HAMA、HAMD评分即出现明显改善,帕罗西汀组在第4周评分才开始有改善(HAMD为第3周),至治疗结束,3组间PASS总分差异无统计学意义;阿普唑仑组、帕罗西汀组及合用组有效率(%)及治愈率(%)分别为88.9,89.3,92.9,和59.3,60.7,60.7,差异无统计学意义;阿普唑仑组、帕罗西汀组不良反应发生率为51.9%和25%,而合用组仅为14.3%,明显低于前两组。结论阿普唑仑、帕罗西汀早期联合使用治疗惊恐障碍急性期快速、安全、高效,优于单一使用。     

Factors Associated with Treatment Outcomes in Mindfulness-Based Cognitive Therapy for Panic Disorder

Purpose

Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce.

Materials and Methods

Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks.

Results

Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT.

Conclusion

Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.     

62例惊恐障碍患者的功能状况和首诊情况调查

目的探讨惊恐障碍患者的功能状况及首诊情况。方法收集河北省第六人民医院门诊及住院惊恐障碍患者共62例,采用功能大体评定量表(GAF)评价功能状况,以自制一般情况调查表评定分析惊恐障碍患者的临床特征及首诊情况。结果惊恐障碍患者平均年龄39.9岁,男女之比为1∶1.58,有41例(66.1%)病前12个月有生活事件,其工作能力、日常生活、精神状况、社会交往、自我料理等功能状况都受到不同程度的影响,尤其以精神状况、工作能力、日常生活方面明显,受中等程度以上影响的比例分别为91.9%、80.6%和77.4%。62例患者均首诊于综合医院非精神科,有49例(79.0%)被诊断为心脏病,且合并诊断较多,在临床症状中,大多数患者表现心悸、头晕、呼吸急促、出汗、堵塞感、胸部不适等5个以上的急性躯体不适症状(82.3%)。结论惊恐障碍患者社会功能受损明显,多首诊于综合医院的非精神科,常常不能被识别,容易造成误诊、漏诊,并做大量辅助检查,临床医生一定要全面掌握病情,熟悉惊恐障碍的躯体症状特点,遵循生物-心理-社会医学模式,以利于疾病的早期诊断,改善患者的社会功能。     

文拉法辛缓释剂对首发惊恐障碍的疗效及安全性观察

目的观察文拉法辛缓释剂治疗首发惊恐障碍的治疗效果和安全性。方法对37例门诊首发惊恐障碍患者予以文拉法辛缓释剂治疗观察共6周,治疗前后采用汉密尔顿焦虑量表（HAMA,14项）评分观察疗效和国内统一4级疗效评定和比较,以及观察记录不良反应。结果①文拉法辛缓释剂治疗惊恐障碍的临床治愈率和总有效率分别为70.2%和91.9%。文拉法辛缓释剂治疗后的总分在第一周末就已经开始下降,并且差异有显著性（t=11.35,P〈0.05）;②37例患者治疗前后HAMA评分有明显改变,治疗过程中各时段两量表评分比较,差异均有显著性（P〈0.05）,并且文拉法辛缓释剂的疗效随治疗时间的延长而提高;③服药治疗6周后近90%患者的不良反应会自行缓解。结论文拉法辛缓释剂具有起效快,疗效好,安全性高,副作用轻微,依从性好的特点,不失为治疗首发惊恐障碍的首选药物。     

惊恐障碍患者的父母育龄与胎次效应分析

目的探讨惊恐障碍患者的父母育龄与胎次效应。方法采用Haldane和Smith的方法,对75例惊恐障碍患者的家系进行了分析。结果惊恐障碍患者的父母育龄与胎次效应显著（X=2．56,P〈0．02）,结论父母育龄越大及胎次高者易患此病。