强迫症患者大脑灰质体积变化——基于体素的形态学分析

目的探讨强迫症(OCD)患者大脑灰质体积的变化,并分析其在发病过程中可能存在的相关机制。方法选择31例年龄17～47岁重度强迫症患者和31例正常对照被试者,获取脑结构磁共振T1图像,使用基于体素的形态学测量(VBM)方法,比较强迫症组和对照组大脑灰质体积的差异,并将患者灰质体积差异区与其临床评分进行相关分析。结果与对照组相比,OCD患者在左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回处体积显著减小。左侧壳核和岛叶的体积与患者贝克焦虑量表(BAI)评分成显著负相关。结论左侧壳核、岛叶、运动前区、顶上小叶以及右侧角回的灰质体积变化影响了该脑区功能,从而导致了OCD患者的部分症状。其中左侧壳核以及岛叶的损伤与患者焦虑情绪的异常密切相关。     

Voxel-based morphometry study of gray matter abnormalities in obsessive-compulsive disorder

To examine regional abnormalities in the brains of patients with obsessive-compulsive disorder (OCD), we assessed the gray matter (GM) density using voxel-based morphometry (VBM). We compared magnetic resonance images (MRIs) acquired from 71 OCD patients and 71 age- and gender-matched normal controls and examined the relationship between GM density and various clinical variables in OCD patients. We also investigated whether GM density differs among the subtypes of OCD compared to healthy controls. We detected significant reduction of GM in the inferior frontal gyrus, the medial frontal gyrus, the insula, the cingulate gyrus, and the superior temporal gyrus of OCD patients. A significant increase in GM density was observed in the postcentral gyrus, the thalamus, and the putamen. Some of these regions, including the insular and postcentral gyrus, were also associated with the severity of obsessive- compulsive symptoms. These findings indicate that the frontal-subcortical circuitry is dysfunctional in OCD, and suggest that the parietal cortex may play a role in the pathophysiology of this disease.     

Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder

Probands affected with eating disorders (ED) present a higher number of relatives affected with obsessive-compulsive disorders/tic disorders than a comparison population. Therefore, we hypothesized that ED and obsessive-compulsive disorder (OCD) might share the same biological liability, and that a single major gene might account for that liability. We tested this hypothesis by applying a complex segregation analysis to 141 families of probands affected with ED (89 with anorexia nervosa, restricting and binge-eating types, 52 with bulimia nervosa). Given the hypothesized relationship between OCD and genetic spectrum disorders, we considered these diagnoses as affected phenotype in relatives. In Italian ED families, ED and OCD followed a Mendelian dominant model of transmission. When probands were divided according to co-diagnosis of OCD, best fit in the subgroup of families of 114 probands without OCD co-diagnosis was for a Mendelian dominant model of transmission whereas a Mendelian additive model of transmission represented best fit in the subgroup of families of 27 probands with an OCD co-diagnosis. Genetic transmission was not shown in those families where the only affected phenotype was ED. The existence of a Mendelian mode of genetic transmission within ED families supports the hypothesis that a common genetic liability could account for both ED and OCD.     

Medial frontal and dorsal cortical morphometric abnormalities are related to obsessive-compulsive disorder

Whole-brain voxel-based morphometry (VBM) studies provide support for orbitofrontal, medial frontal as well as for dorsal cortical volumetric alteration in obsessive-compulsive disorder (OCD). However, there is still a need to replicate a priori unpredicted findings and to elucidate white matter volumetric abnormalities and relationships between grey (GM) and white (WM) matter volume and clinical characteristics of OCD. We compared GM and WM volume in a group of 14 patients with OCD and 15 healthy controls using a 3 T MRI scanner and an optimized VBM protocol. Regression analysis was used to examine relationships between GM and WM volume and clinical variables. In OCD we have found total WM volume reduction and marked mediofrontal, right temporo-parieto-occipital, right precentral, left middle temporal, left cerebellar and bilateral pons and mesencephalon GM volume reduction in the voxel-based analysis (p ≤ 0.05, FDR corrected, extent threshold 100 voxels). Regression analysis indicated a positive relationship between left orbitofrontal GM volume and severity of obsessive-compulsive symptoms and a negative relationship between symptom severity and GM volume in supramarginal gyri. Earlier age of OCD onset and longer illness duration were associated with smaller left occipital GM and right parietal WM and with greater left medial frontal GM and left frontal WM (p ≤ 0.001, uncorrected, extent threshold 50 voxels). Our results confirm volumetric abnormalities in the medial frontal and dorsal cortical areas in OCD. The relationships between OCD and clinical variables provide further evidence that frontal, parietal and occipital structures play a role in the disorder.     

Saccadic instabilities in albinism without nystagmus

Albinism effects a surprising manipulation of the visual pathway in which some of the normally uncrossed axons of the temporal retina instead cross at the chiasm. An expected consequence of this misrouting is that subjects with albinism will have difficulty in specifying the targets of saccades. Usually albinos have nystagmus so the stability of their saccadic eye movements is not readily accessible, but some albinos do not have nystagmus. In these subjects it was found that they had frequent saccadic intrusions, the sizes of which were correlated with velocities of steady drifts in fixations (r = 0.802, P < 0.05). An explanation for the correlation between the amplitudes of the intrusions and the velocities of the drifts is that it is due to a common failure in the development of a saccadic system which is responsible for converting a given retinal displacement into a matching eye movement, with the extent of the failure reflecting the severity of the misrouting.     

Gender in obsessive-compulsive disorder and obsessive-compulsive spectrum disorders

Summary Background: There is increasing recognition that obsessive-compulsive disorder (OCD) and putative OCD spectrum disorders (OCSDs) are not homogenous entities. Gender may provide an important window onto the heterogeneity of these various disorders. Methods: A MEDLINE review of gender issues in OCD and putative OCD spectrum disorders (excluding eating disorders) was undertaken (1965–2000). These included demographic variables, clinical phenomenology, etiological factors, and treatment implications. Results: OCD differs from other anxiety disorders in having an approximately equal male:female gender ratio. OCSDs (e.g. body dysmorphic disorder) may have an equal gender ratio, may be more common in women (e.g. trichotillomania, hypochondriasis) or may be more common in men (e.g. Tourette's disorder). Etiological factors may differ across gender; an association between perinatal or early brain injury and OCD or Tourette's appears particularly important in males, while OCD and trichotillomania may also begin during pregnancy or shortly after childbirth with exacerbation of symptoms during menstruation. It is not clear that anti-androgens are effective in OCD, nor that gender predicts response to serotonin reuptake inhibitors in this disorder. Conclusion: There is a relative scarcity of literature addressing gender issues in OCD and putative OCSDs. That literature which does exist is not entirely conclusive, but raises a number of interesting questions for future research.     

Thought disorder in patients with obsessive-compulsive disorder

We examined the presence of disordered thinking/perception in patients with obsessive-compulsive disorder (OCD). Recently, an obsession model has been proposed, which classifies obsessions into two different subtypes: autogenous obsessions and reactive obsessions (Lee & Kwon, 2003). Based on this model, we hypothesized that OCD patients primarily displaying autogenous obsessions as opposed to reactive obsessions would display more severely disordered thinking/perception. We compared 15 OCD patients primarily displaying autogenous obsessions (AOs), 14 OCD patients primarily displaying reactive obsessions (ROs), 32 patients with schizophrenia (SPRs), and 28 patients with other anxiety disorders (OADs) with respect to thought disorders as assessed by the Comprehensive System of the Rorschach Inkblot Test. Results indicated that both AOs and SPRs displayed more severe thought disorders compared to ROs or OADs. Theoretical and clinical implications are discussed.     

Premenstrual dysphoric disorder and psychiatric co-morbidity

Summary Premenstrual dysphoric disorder (PMDD) can occur co-morbidly with other axis I disorders, particularly mood and anxiety disorders. The data supporting this diagnostic dilemma are reviewed in terms of methodological comparisons between studies. The point prevalence of the co-occurrence of PMDD and other psychiatric disorders is discussed as well as implications for treatment and further study.     

单一认知行为治疗对强迫障碍患者的疗效

目的:验证操作手册指导下的认知行为治疗(CBT)对未服药强迫障碍患者的疗效和可接受性.方法:纳入符合美国精神障碍诊断和统计手册第4版(DSM-IV)强迫障碍诊断标准的门诊患者17例,在自行编制强迫障碍CBT操作手册指导下进行12周个别治疗.应用耶鲁-布朗强迫量表(Y-BOCS)、汉密顿抑郁量表(HAMD)和汉密顿焦虑量表(HAMA)分别于基线和12周治疗结束时进行临床症状评估.研究期间不服用任何精神药物.结果:17例强迫障碍患者中有14例完成了12次治疗(脱落率为17.6％).12周治疗结束时,Y-BOCS总分由(22.4±5.9)下降至(9.7±6.0)分,HAMD分由(9.2±4.2)下降至(4.6±3.7),HAMA分由(14.1±4.7)下降至(5.9±4.6),均P＜0.01.按照意向性治疗的统计方法,CBT对强迫障碍的有效率为70.6％ (12/17),缓解率为52.9％ (9/17).结论:手册指导下的单一认知行为治疗能显著改善强迫障碍患者的强迫症状、焦虑和抑郁情绪,且患者对该疗法的接受度较高,治疗依从性较好.     

Saccadic inhibition among schizotypal personality disorder subjects

Schizotypal personality disorder (SPD) is theoretically part of the schizophrenia spectrum both clinically and neurobiologically. A liability for developing schizophrenia may be associated with dysfunction of dorsolateral prefrontal cortex (DLPFC) and its cortical and/or subcortical circuitry. If so, abnormalities on tasks associated with DLPFC functioning among SPD subjects would support the thesis that SPD is neurobiologically related to schizophrenia. Antisaccade and ocular motor delayed response performance, both of which are ostensibly supported by DLPFC circuitry, were assessed among 29 SPD, 17 schizophrenia, and 25 normal subjects. Generally, the SPD subjects' performance was more similar to normal than to schizophrenia groups. There was evidence, however, for inhibition abnormalities in a subgroup of SPD subjects. Antisaccade performance identified more SPD subjects as "abnormal" than delayed response measures.     

Pharmacotherapy for obsessive-compulsive disorder

Pharmacotherapeutic options for obsessive-compulsive disorder (OCD) have expanded over the past half-century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first-line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment-refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device-based approaches for treatment-refractory OCD are reviewed.     

Obsessive-compulsive disorder and separation anxiety co-morbidity in early onset panic disorder.

BACKGROUND: This study was undertaken to examine the relationship between anxiety co-morbidity and age of onset of panic disorder. METHODS: Age of onset of panic disorder and co-morbid anxiety disorders were assessed among 201 panic disorder probands with childhood separation anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, social phobia and specific phobia as part of a clinician-administered lifetime diagnostic interview. A generalized linear model was used to test the association between each anxiety co-morbidity and age of panic disorder onset while simultaneously controlling for the potential confounding effects of sociodemographic characteristics and other psychiatric co-morbidity. RESULTS: Earlier onset of panic disorder was found in patients with co-morbid obsessive-compulsive disorder, obsessive-compulsive symptoms and separation anxiety disorder, but not simple phobia or social phobia. Patients with both childhood separation anxiety disorder and obsessive-compulsive disorder had an even earlier panic onset than those with either childhood separation anxiety disorder or obsessive-compulsive disorder. CONCLUSIONS: The association between anxiety co-morbidity and earlier onset of panic disorder is specific to obsessive-compulsive disorder and childhood separation anxiety disorder.     

Depression in comorbid obsessive-compulsive disorder and posttraumatic stress disorder

Previous findings suggested a unique role that depression symptoms might play in the comorbid relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). However, the nature of this role remains unclear. Thus, the current study examined ways in which OCD and PTSD symptoms vary as a function of depression, as well as the mediating role of depression in the OCD-PTSD relationship, in 104 individuals seeking treatment for refractory OCD. Findings revealed that depressed individuals in the treatment-refractory OCD sample report higher levels of overall obsessing and greater severity of PTSD. In addition, depression appeared to mediate the relation between OCD and PTSD. Implications of findings are discussed.     

Drug treatment of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) traditionally has been considered a rare, treatment refractory disorder of psychological origin. However, OCD appears to be much more common than was previously believed. Moreover, in recent years controlled studies demonstrated that clomipramine is more effective than placebo and than other tricyclics for reducing obsessive-compulsive symptoms. Although it has been suggested that clomipramine was effective in treating obsessive-compulsive symptoms by an antidepressant mechanism, the majority of the controlled studies found that its antiobsessional effects occurred whether the patient was depressed or not. The apparent specificity of clomipramine, and, to some extent, newer serotonin selective antidepressants, suggests a serotonergic role in the psychobiology of OCD.     

Impairment of olfactory identification in obsessive-compulsive disorder

BACKGROUND: Olfactory identification ability has been associated with processing in the orbitofrontal cortex (OFC), an area that has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Although olfactory sensitivity is normal in patients with OCD, no study has investigated olfactory identification in this disorder. METHODS: A group of 20 subjects with OCD and 23 age- and education-matched controls performed a standardized test of olfactory identification. They also performed computerized tests of spatial memory span, spatial working memory and spatial recognition memory that have been shown previously to be sensitive to cognitive deficits in patients with OCD. RESULTS: Performance on the olfactory identification task, spatial recognition task and spatial span task was significantly worse in the OCD group than controls. CONCLUSIONS: While impairment in spatial cognition is consistent with previous studies of OCD, its significance for brain-behaviour models of OCD is unclear. However, the finding of abnormal olfactory identification in patients with OCD is consistent with the hypothesis that there is a disruption to processing at the level of the OFC in the disorder.     

Family accommodation in pediatric obsessive-compulsive disorder.

Despite the importance of the family in the treatment of pediatric obsessive-compulsive disorder (OCD), relatively little empirical attention has been directed to family accommodation of symptoms. This study examined the relations among family accommodation, OCD symptom severity, functional impairment, and internalizing and externalizing behavior problems in a sample of 57 clinic-referred youth 7 to 17 years old (M = 12.99 +/- 2.54) with OCD. Family accommodation was a frequent event across families. Family accommodation was positively related to symptom severity, parent-rated functional impairment (but not child-rated impairment), and externalizing and internalizing behavior problems. Family accommodation mediated the relation between symptom severity and parent-rated functional impairment.     

Strategy implementation in obsessive-compulsive disorder and trichotillomania

BACKGROUND: The use of strategies to aid performance when undertaking neuropsychological tasks is dependent on intact fronto-striatal circuitry, and growing evidence suggests impaired spontaneous use of strategies in patients with obsessive-compulsive disorder (OCD). However, studies to date have not examined the effects of strategy training on task performance in OCD or in trichotillomania (compulsive hair-pulling, a condition that has been argued to share overlap with OCD in terms of phenomenology and co-morbidity). METHOD: The ability to generate novel visuospatial sequences using a computer interface was examined before and after undertaking optimal strategy training in 20 OCD patients, 17 trichotillomania patients, and 20 controls (matched for age, education, and IQ). RESULTS: OCD patients failed to improve ability to generate novel sequences above baseline despite successfully completing strategy training to the same extent as other groups. In contrast, performance of trichotillomania patients improved significantly after training to the same extent as controls. Groups did not differ on memory span, trial-by-trial action monitoring, or ability to generate novel visuospatial sequences prior to strategy training. CONCLUSIONS: Strategy implementation deficits, suggestive of cognitive inflexibility and fronto-striatal dysfunction, appear integral to the neurocognitive profile of OCD but not trichotillomania. Future research should investigate cognitive flexibility in obsessive-compulsive spectrum disorders using a variety of paradigms, and clarify the contribution of specific neural structures and transmitter systems to deficits reported.