Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder.

BACKGROUND: Family-based evidence for association at serotonin system genes SLC6A4, HTR1B, HTR2A, and brain-derived neurotrophic factor (BDNF) has been previously reported in obsessive-compulsive disorder (OCD). Early-onset OCD is a more familial form of the disorder. METHODS: We used the transmission-disequilibrium test of association at common polymorphisms in each of these genes in 54 parent-child trios ascertained through probands with early-onset OCD. RESULTS: No evidence for association was detected at any of the polymorphisms in the entire set of subjects. Nominally significant association was found at the HTR2A rs6311 polymorphism in subjects with tic disorder and OCD (p = .05), replicating a previous finding in Tourette syndrome and OCD. Nominally significant association was also found for the SLC6A4 HT transporter gene-linked polymorphic region (5-HTTLPR) polymorphism for female subjects (p = .03). Neither association would remain significant after statistical correction for multiple testing. Despite no individual study reporting replication, a pooled analysis of five replication studies of the SLC6A4 5-HTTLPR polymorphism supports association (p = .02). CONCLUSIONS: Low power across individual association studies in OCD may lead to a false acceptance of the null hypothesis. Accumulation of evidence from multiple studies will be necessary to evaluate the potential role for these genes in contributing to susceptibility to OCD.     

HPA axis disturbance in obsessive-compulsive disorder

Twenty nondepressed outpatients with DSM-III obsessive-compulsive disorder entered a 10-week placebo-controlled study of clomipramine and underwent a 1-mg dexamethasone suppression test (DST) at baseline; 11 had a repeat DST at the end of treatment. Nonsuppression was rare. When compared to 82 previously described outpatients with panic disorder studied in a similar fashion, OCD patients had postdexamethasone cortisol values that were substantially lower and more stable over time. Results within the OCD group closely resembled those from a group of never-ill controls.     

难治性与非难治性强迫症患者生活质量比较研究

目的:比较难治性与非难治性强迫症患者生活质量差异。方法:采用汤旦林(TDL)生活质量量表评估51例难治性强迫症患者和59例非难治性强迫症患者的生活质量。结果:难治性强迫症的社会方面、尽职的能力、自我健康较非难治性强迫症差(t=2.230,P<0.05;t=2.328,P<0.05;t=2.177,P<0.05),而两组身体方面、心理方面及TDL量表总分差异均无统计学意义(t=0.937,P>0.05;t=0.917,P>0.05;t=1.649,P>0.05)。结论:难治性强迫症患者生活质量较非难治性强迫症差。     

Response to high doses of citalopram in treatment-resistant obsessive-compulsive disorder

We report a severe case of obsessive-compulsive disorder (OCD) that responded to very high doses of citalopram (160mg/day) after a poor response to clomipramine 250 mg/day for several years, alone or in combination with buspirone 30 mg/day or flupenthixol 4 mg/day. The patient had previously been submitted for capsulotomy which was declined, probably due to the magical content of her obsessions, which resembled delusions.     

The clinical features of Tourette's disorder with obsessive-compulsive symptoms

Twenty-three patients with Tourette's disorder (13 with obsessive-compulsive symptoms [OCS] and 10 without) were comparatively investigated. In contrast to OCS-free Tourette's disorder patients, those with OCS were found to be characterized by (i) a higher incidence of volatile temper, (ii) a higher incidence of compulsive tics, (iii) a higher incidence of perinatal disorders and brain wave abnormalities, (iv) a higher severity as rated using the Seventy Scale, and (v) a higher prevalence of complications, especially of developmental disorders. Of the subjects with OCS-accompanied Tourette's disorder, approximately half had developed OCS by the onset of tics. These findings suggest the likelihood that OCS-accompanied Tourette's disorder is more strongly associated with organic cerebral disorders, independently of sites of tic disorders, than is OCS-free Tourette's disorder.     

Use of the selective serotonin reuptake inhibitor citalopram in a possible animal analogue of obsessive-compulsive disorder

Canine acral lick dermatitis (ALD) has been suggested as an animal analogue of obsessive-compulsive disorder (OCD). A series of dogs with ALD or similar conditions were treated with citalopram, the most selective of the selective serotonin reuptake inhibitors. Six of nine (66.7%) dogs showed significant improvement. Given the apparent efficacy of citalopram in the treatment of OCD and related disorders, these data provide further evidence that ALD is a useful animal analogue of OCD. Depression and Anxiety 8:39–42, 1998. © 1998 Wiley-Liss, Inc.     

奎硫平治疗强迫症的辅助作用

目的：探讨奎硫平辅助治疗强迫症的临床疗效和安全性。方法：对48例强迫症患者,在服用原抗抑郁药的基础上随机分为奎硫平组和安慰剂组,分别给予合用奎硫平和安慰剂。疗程12周。采用Yale-Brown强迫症量表（Y-BOCS）和治疗中出现的症状量表（TESS）评定疗效和不良反应。结果：奎硫平组Y-BOCS评分治疗后有显著下降,安慰剂组则无差异;治疗后Y-BOCS评分以奎硫平组显著较低。两组TESS评分相仿。结论：抗抑郁药合用奎硫平治疗强迫症有一定辅助作用。     

Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder

The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.     

Comorbidity in obsessive-compulsive disorder: focus on depression

The authors investigated the comorbidity between obsessive-compulsive disorder (OCD) and other psychiatric disorders in a group of 154 outpatients. The influence of an associate major depressive disorder (MDD) on the outcome of treatment with clomipramine was examined in a subgroup of 52 patients. The results showed that MDD was the most frequent disorder associated with OCD (almost 20% of the patients), followed by generalized anxiety and panic disorder. The co-presence of depression delayed the effect of clomipramine.     

青少年期起病的双相障碍与强迫症共病研究

目的：探讨青少年期起病的双相障碍与强迫症共病患者的临床特征。方法：选择双相障碍和强迫症共病患者（共病组）36例及强迫症患者（OCD组）31例,完成自编调查问卷、强迫症量表（Y-BOCS）测评。结果：OCD组的男性比例高于共病组;共病组的强迫症病程、平均治疗时间长于OCD组。结论：双相障碍与强迫症共病是常见的临床现象,共病对患者的病程及疗效均有影响。     

The rates of co-occurring behavioural addictions in treatment-seeking individuals with obsessive-compulsive disorder: a preliminary report

Abstract

Objectives: To assess the rates of co-occurring putative ‘behavioural addictions’ in patients with obsessive-compulsive disorder (OCD).

Methods: Twenty-three international centres specialising in the treatment of OCD were invited to participate in a survey of the rates of behavioural addictions and other relevant comorbidity within their samples.

Results: Sixteen of 23 (69.6%) invited centres from 13 countries had sufficient data to participate in the survey. The use of validated diagnostic tools was discrepant, with most centres relying on a ‘clinical diagnosis’ to diagnose behavioural addictions. The final sample comprised of 6916 patients with a primary diagnosis of OCD. The reported rates of behavioural addictions were as follows: 8.7% for problematic internet use, 6.8% for compulsive sexual behaviour disorder, 6.4% for compulsive buying, 4.1% for gambling disorder and 3.4% for internet gaming disorder.

Conclusions: Behavioural addictions should be better assessed for patients with OCD. The absence of diagnostic scales developed specifically for behavioural addictions and overlapping obsessive-compulsive phenomena such as compulsive checking of information on the internet may explain the relatively high rate of problematic internet use in this sample. The study encourages better efforts to assess and to conceptualise the relatedness of behavioural addictions to obsessive-compulsive ‘spectrum’ disorders.     

The cost of obsessive-compulsive disorder (OCD) in China: a multi-center cross-sectional survey based on hospitals

BackgroundObsessive-compulsive disorder (OCD) is considered a very debilitating disorder with severe loss of quality of life and income.AimsThis study estimates the quality of life and economic consequences of OCD in China.MethodsThe research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China. The direct method was used to get the direct cost of OCD. Indirect costs associated with OCD were estimated using the human capital approach. Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost. Sensitivity analysis was used to analyse the uncertainty of total cost.ResultsThe mean quality of life score for OCD was 52.78 (20.46). The annual total cost of OCD per capita was 24 503.78 (95% CI: 22 621.53 to 26 386.03) renminbi (RMB) (US$3465.88 (95% CI: US$3199.65 to US$3732.11)). The annual cost of OCD in China was estimated to be 37.74 billion (95% CI: 34.95 billion to 40.53 billion) RMB (equal to US$5.34 billion (95% CI: US$4.94 billion to US$5.73 billion)). Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB (US$3.27 billion) and 370.00 billion RMB (US$52.33 billion). Worse social function status, more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale (Y-BOCS) score were associated with worse quality of life. The numbers of clinic visits and hospitalisations, socioeconomic status, education, Y-BOCS scores and age were found to be significantly associated with total cost.ConclusionsOCD is associated with low quality of life and high costs in China. The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis, the provision of evidence-based treatments and relapse prevention strategies.     

中国汉族人群5-羟色胺2C受体基因rs518147位点多态性与强迫症的关联性

目的:探讨中国汉族群体5-羟色胺2C受体基因(5-HTR2C)启动区相关单核苷酸多态(SNP)位点rs518147多态性的分布状况及其与强迫症之间的关系。方法:采用直接测序法分析中国汉族群体符合中国精神障碍分类与诊断标准第3版或国际疾病分类第10版强迫症诊断标准的患者308例(强迫症组:男123例,女185例)和410名健康对照(对照组:男175名,女235名)5-HTR2Crs518147位点半合子(男性)或基因型(女性)分布频率,并分析半合子(男性)或基因型(女性)分布频率与强迫症发病的遗传易感性的关系。结果:强迫症组中5-HTR2C启动区rs518147位点男性患者携带G半合子与女性患者携带G+(GG与GC)基因型的比率均显著高于对照组(男性:χ2=4.973,P=0.026;女性:χ2=5.243,P=0.022),G等位基因的频率明显高于对照组(χ2=4.611,P=0.032)。结论:中国汉族群体中5-HTR2C启动区rs518147位点多态性可能与强迫症遗传易感性相关。     

米氮平治疗强迫症对照研究

目的:比较米氮平与氟西汀治疗强迫症的疗效和不良反应.方法:分别用米氮平和氟西汀治疗强迫症各27例,疗程8周.应用Yale-Brown强迫症量表(Y-BOCS)、汉密尔顿抑郁量表(HAMD)及汉密尔顿焦虑量表(HAMA)评定疗效.结果:治疗后米氮平组与氟西汀组Y-BOCS、HAMD、HAMA分值均显著下降,两组间疗效差异无显著性.米氮平组不良反应明显少于氟西汀组.结论:米氮平治疗强迫症疗效与氟西汀相仿,不良反应少,可在临床使用.     

A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder.

BACKGROUND: One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor. METHODS: The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject). RESULTS: Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine. CONCLUSIONS: These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.     

Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study

Obsessive-compulsive disorder (OCD) is a common anxiety disorder, which often causes significant impairment of the affected individual's social, occupational or interpersonal functioning. Previous reports suggest that the disorder may be treated with the tricyclic antidepressant clomipramine, and also with the more recently introduced selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, fluvoxamine, sertraline and paroxetine. The present 24-week open pilot study was designed to examine the efficacy, appropriate dose range, side-effects and clinical usefulness of citalopram in OCD. A total of 29 OCD patients were included in the study, of whom 76% showed alleviation of symptoms as evaluated by various self-and observer-rated scales, such as the Yale-Brown Obsessive Compulsive Scale. In most cases the citalopram doses used were in most cases 40 or 60 mg daily, and the treatment was well tolerated. The most commonly experienced adverse events during the study were nausea, vomiting, increased dreaming and decreased sleep. Diminished sexual desire and orgasmic dysfunction were also reported. Despite having the limitations of an open study, our results suggest that citalopram may be effective in the treatment of obsessive-compulsive disorder.     

Dimensional approach to obsessive-compulsive disorder in childhood and adolescence

Based on a review of the charts of child and adolescent psychiatric patients, a group of patients with obsessive-compulsive symptoms and a control group were identified. Obsessive-compulsive symptoms described in the charts were classified according to form using the checklist of Khanna et al. By use of latent trait models, a 6-item obsessive-compulsive rating scale was established revealing a dimensional rather than a categorical distribution of obsessive-compulsive symptoms. The correlation with other clinical features was investigated.     

强迫症患者的注意偏向

目的:探讨强迫症(OCD)患者的注意偏向情况。方法:将32例OCD患者与30例正常人作为研究对象,完成用于评估注意偏向的中国情绪词Stroop任务。结果:在情绪词测验中,OCD组的中性词、负性词和厌恶词反应时长于对照组,差异具有统计学意义(t=-3.101,P=0.003;t=-3.243,P=0.003;t=-3.107,P=0.004);OCD组负性词的注意偏向和厌恶词的注意偏向比较差异无统计学意义(F=0.061,P=0.846)。结论:OCD患者情绪加工存在损害。     

Plasma nitrate values in patients with obsessive-compulsive disorder

Recently there has been increasing evidence that free oxygen species may play an important role in the pathophysiology of various neuropsychiatric disorders. The present study was performed to assess the changes in plasma nitric oxide (NO) levels in patients with obsessive-compulsive disorder (OCD) compared to age- and sex-matched normal controls. Twenty-three patients with OCD and 23 healthy volunteers were included in the study. NO values were determined in the plasma of normal healthy controls and the OCD patients. Plasma nitrate levels in OCD patients were significantly higher than those in controls and were significantly and positively correlated with Yale-Brown Obsession Compulsion Scale scores but not related to age or to the duration of illness. These findings indicated a possible role of increased NO may be relevant to the pathophysiology of OCD.