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.     

The genetic studies of obsessive-compulsive disorder and its future directions

Obsessive-compulsive disorder (OCD) is characterized by recurrent and persistent thoughts (obsessions), and repetitive behaviors or mental acts (compulsions). In Korea, an epidemiological study reported that the lifetime prevalence of OCD in the population was greater than two percent. The exact cause of OCD is still unknown. Evidence from familial, twin and segregation studies supports the role of a genetic component in the etiology of OCD. In addition, there is growing evidence that OCD has a specific neurochemical and neuroanatomical basis. According to this evidence, researchers have selected various candidate genes which have been implicated in the neurophysiology of OCD, and differences of allelic variants in OCD patients and controls have been analyzed. In this review we will introduce the results of previous genetic studies of OCD which have been performed in other populations, including twin studies, family studies, segregation analyses, linkage analyses, and association studies. In addition to these studies, we will present the results of our genetic studies of OCD performed in Korea.     

Comparative cognitive profiles of obsessive-compulsive disorder and schizophrenia

A body of neuropsychological research revealed cognitive impairments in patients suffering from obsessive-compulsive disorder (OCD). Only few investigations addressed the question of how specific these impairments are. The present study compared the performances of 19 subjects with OCD to 19 subjects with schizophrenia and 19 healthy controls on neuropsychological tasks across the main cognitive domains (memory, attention, visual spatial and executive functioning). For purposes of data-reduction, single test measures of the test battery applied were aggregated into eight cognitive domain scores. Contrary to our expectation we found comparable performance profiles of obsessive-compulsive (OC) and schizophrenia subjects across domains with impairments primarily affecting simple attentional skills and memory skills. However, deficits of subjects with schizophrenia were greater in magnitude than those of subjects with OCD on all domains assessed. Elevated depression scores exerted a relevant impact on performance deficits in the OC but not in the schizophrenia sample.     

The somatic marker affecting decisional processes in obsessive-compulsive disorder

Introduction. Patients with obsessive-compulsive disorder (OCD) demonstrate impairment in decisional processes in which both cognition and emotion play a crucial role.

Methods. We investigated the connection between decision-making performances and choice-related skin conductance responses (SCRs), to identify a somatic marker impairment affecting decisional processes in these patients. We explored SCRs during the Iowa Gambling Task in 20 OCD and 18 control, measuring anticipatory and posticipatory psychophysiological reactions according to card choices and to the outcomes of each selection.

Results. Most patients exhibited weaker SCRs compared to HC, although there weren't substantial differences in magnitude between the two groups. In contrast with HC, patients with OCD showed no significant differences of SCRs activation according to card selections; they chose cards from neither favourable nor unfavourable decks.

Conclusions. The main finding of the study were the evidence of a dysfunctional biological marker in OCD subjects, affecting decision-making process. Dysfunctional patterns of SCRs could partially explain OCDs’ impairment in this ability. Decision-making deficits in OCDs could be influenced in part by the lack of somatic differences in discriminating between advantageous and disadvantageous behaviour. These findings could lead to a more complete understanding of OCD.     

A meta-analysis of the relation of intolerance of uncertainty to symptoms of generalized anxiety disorder, major depressive disorder, and obsessive-compulsive disorder

Intolerance of uncertainty (IU) has been suggested to reflect a specific risk factor for generalized anxiety disorder (GAD), but there have been no systematic attempts to evaluate the specificity of IU to GAD. This meta-analysis examined the cross-sectional association of IU with symptoms of GAD, major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). Random effects analyses were conducted for two common definitions of IU, one that has predominated in studies of GAD (56 effect sizes) and another that has been favored in studies of OCD (29 effect sizes). Using the definition of IU developed for GAD, IU shared a mean correlation of .57 with GAD, .53 with MDD, and .50 with OCD. Using the alternate definition developed for OCD, IU shared a mean correlation of .46 with MDD and .42 with OCD, with no studies available for GAD. Post-hoc significance tests revealed that IU was more strongly related to GAD than to OCD when the GAD-specific definition of IU was used. No other differences were found in the magnitude of associations between IU and the three syndromes. We discuss implications of these findings for models of shared and specific features of emotional disorders and for future research efforts.     

Characteristics of open- and closed-loop smooth pursuit responses among obsessive-compulsive disorder, schizophrenia, and nonpsychiatric individuals

Twenty obsessive-compulsive disorder patients and comparison samples of 20 schizophrenia and 20 nonpsychiatric individuals were presented with (a) a step-ramp task designed to measure smooth pursuit initiation and (b) a regular ramp task designed to measure steady-stale tracking performance. Obsessive-compulsive disorder and non-psychiatric individuals had statistically similar pursuit reaction time and average eye accelerations during the open-loop interval. They also had similar closed-loop performance. Schizophrenia patients, however, had delayed pursuit reaction times and reduced eye acceleration during the last 60 ms of the open-loop interval. These findings suggest that brain regions supporting smooth pursuit performance are unimpaired among obsessive-compulsive disorder patients. Furthermore, the deficits found in the schizophrenia patients replicate and extend the results of previous smooth pursuit studies.     

Power spectral EEG analysis and EEG variability in obsessive-compulsive disorder

Spectral EEG characteristics of thirteen patients with severe Obsessive-Compulsive Disorder (OCD) were investigated topographically. The finding of predominantly left posterior frontal to mid-temporal theta-2 is discussed in light of previous EEG studies and recent neuroradiologic findings.     

Functional connectivity in fronto-subcortical circuitry during the resting state in obsessive-compulsive disorder

Obsessions and compulsions mediated by cognitive inflexibility might be associated with abnormal resting state functional connectivity in the default mode network (DMN) that represents intrinsically generated neuronal activity. It was hypothesized that decreased functional connectivity in the DMN would occur in components of fronto-subcortical circuits in patients with obsessive-compulsive disorder (OCD). Twenty-two unmedicated OCD patients and 22 age- and sex-matched healthy controls received resting state functional scanning runs. The posterior cingulate cortex (PCC) region was chosen as the seed region for the connectivity analysis. Correlations between temporal connectivity with the seed region and scores on clinical measures and obsessive-compulsive symptom dimensions were also assessed. OCD patients demonstrated less functional connectivity within the DMN in the anterior cingulate cortex, middle frontal gyrus, and putamen compared to controls. The functional connectivity to the PCC seed region in OCD patients was in the direction opposite to that in the prefrontal areas with regard to scores on cleaning and obsessions/checking dimensions of OCD. These data provide evidence for fronto-subcortical dysfunction in OCD. Results from this study also support the notion that OCD is a heterogeneous disorder mediated by distinct circuits.     

Performance monitoring and error significance in patients with obsessive-compulsive disorder

Performance monitoring has been consistently found to be overactive in obsessive-compulsive disorder (OCD). The present study examines whether performance monitoring in OCD is adjusted with error significance. Therefore, errors in a flanker task were followed by neutral (standard condition) or punishment feedbacks (punishment condition). In the standard condition patients had significantly larger error-related negativity (ERN) and correct-related negativity (CRN) ampliudes than controls. But, in the punishment condition groups did not differ in ERN and CRN amplitudes. While healthy controls showed an amplitude enhancement between standard and punishment condition, OCD patients showed no variation. In contrast, group differences were not found for the error positivity (Pe): both groups had larger Pe amplitudes in the punishment condition. Results confirm earlier findings of overactive error monitoring in OCD. The absence of a variation with error significance might indicate that OCD patients are unable to down-regulate their monitoring activity according to external requirements.     

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.     

Risk factors for early treatment discontinuation in patients with obsessive-compulsive disorder

INTRODUCTION:

In obsessive-compulsive disorder, early treatment discontinuation can hamper the effectiveness of first-line treatments.

OBJECTIVE:

This study aimed to investigate the clinical correlates of early treatment discontinuation among obsessive-compulsive disorder patients.

METHODS:

A group of patients who stopped taking selective serotonin reuptake inhibitors (SSRIs) or stopped participating in cognitive behavioral therapy before completion of the first twelve weeks (total n = 41; n = 16 for cognitive behavioral therapy and n = 25 for SSRIs) were compared with a paired sample of compliant patients (n = 41). Demographic and clinical characteristics were obtained at baseline using structured clinical interviews. Chi-square and Mann-Whitney tests were used when indicated. Variables presenting a p value <0.15 for the difference between groups were selected for inclusion in a logistic regression analysis that used an interaction model with treatment dropout as the response variable.

RESULTS:

Agoraphobia was only present in one (2.4%) patient who completed the twelve-week therapy, whereas it was present in six (15.0%) patients who dropped out (p = 0.044). Social phobia was present in eight (19.5%) patients who completed the twelve-week therapy and eighteen (45%) patients who dropped out (p = 0.014). Generalized anxiety disorder was present in eight (19.5%) patients who completed the twelve-week therapy and twenty (50%) dropouts (p = 0.004), and somatization disorder was not present in any of the patients who completed the twelve-week therapy; however, it was present in six (15%) dropouts (p = 0.010). According to the logistic regression model, treatment modality (p = 0.05), agoraphobia, the Brown Assessment of Beliefs Scale scores (p = 0.03) and the Beck Anxiety Inventory (p = 0.02) scores were significantly associated with the probability of treatment discontinuation irrespective of interactions with other variables.

DISCUSSION AND CONCLUSION:

Early treatment discontinuation is a common phenomenon in obsessive-compulsive disorder patients from our therapeutic setting. Psychiatric comorbidities were associated with discontinuation rates of specific treatments. Future studies might use this information to improve management for increased compliance and treatment effectiveness.     

Early versus late onset obsessive-compulsive disorder: evidence for distinct subtypes

The distinction between early versus late onset is important for understanding many different kinds of disorders. In an effort to identify etiologically homogeneous subtypes of obsessive-compulsive disorder (OCD), numerous studies have investigated whether early onset OCD (EO) can be reliably distinguished from a comparatively later onset form of the disorder (LO). The present article presents a systematic review and evaluation of this subtyping scheme, including meta-analyses and re-analyses of raw data. Regarding the latter, latent class analyses of nine datasets, including clinical and community samples, consistently indicated that age-of-onset is not a unimodal phenomena. Evidence suggests that there are two distinguishable groups; EO (mean onset 11 years) and LO (mean onset 23 years). Approximately three-quarters of cases of OCD (76%) were classified as EO. Meta-analyses indicated that EO, compared to LO, is (a) more likely to occur in males, (b) associated with greater OCD global severity and higher prevalence of most types of OC symptoms, (c) more likely to be comorbid with tics and possibly with other putative obsessive-compulsive spectrum disorders, and (d) associated with a greater prevalence of OCD in first-degree relatives. EO and LO were also distinguishable on other psychosocial and biological variables. Overall, results support the view that EO and LO are distinct subtypes of OCD. Comparisons with other, potentially overlapping OCD subtyping schemes are discussed, implications for DSM-V are considered, and important directions for future investigation are proposed.     

人大脑内囊的影像解剖

目的 探讨正常汉族成人内囊的影像解剖。方法 选择健康汉族成人1000名(2000侧),按年龄18~30、31~40、41~50、51~60、61~80岁分为5组,每组男、女各100名。所有受试者均行三维（3D）磁化强度预备梯度回波序列T1WI,应用3D分析软件（Midobl）手工勾画出各个解剖值,软件自动计算出其解剖参数值。
结果 左、右侧内囊前肢前后径测量值为（16.93±1.67）mm和（16.60±1.72）mm,左、右侧内囊后肢前后径测量值为（28.42±1.92）mm和（27.68±1.81）mm。 左、右侧内囊前肢左右径测量值分别为（11.25±1.52）mm及（11.10±1.53）mm,左、右侧内囊后肢左右径测量值分别为（20.10±2.33）mm及（19.44±2.17）mm。 标准轴面上,左、右侧内囊前后肢之间夹角分别为（125.66±2.38）°及（126.01±34.11）°。 结论 高分辨率MRI能提供较为精确的内囊图像及测量数据,本实验提供了中国汉族正常成人内囊的参考值范围。     

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。     

Prestimulus top-down reflection of obsessive-compulsive disorder in EEG frontal theta and occipital alpha oscillations

It has recently been reported that prestimulus electroencephalogram (EEG) frontal theta and occipital alpha oscillations of healthy controls were modulated by the type of upcoming tasks, reflecting prestimulus top-down preparation. The present study explored the differences in dynamics of frontal theta and occipital alpha activities between obsessive-compulsive disorder (OCD) patients and healthy participants in terms of reflection of prestimulus top-down regulation. EEGs were recorded from 16 OCD patients and 16 healthy controls using a color and a shape discrimination task. The power and time course of oscillatory activity were calculated by convolving the EEG signals with Morlet wavelets. Although OCD patients yielded significantly lower total alpha and total theta power results than the normal controls, they demonstrated that significantly higher total alpha and total theta power preceded the difficult task (shape-task) as compared to the easy task (color-task). Furthermore, the frontal region, where OCD patients usually revealed abnormalities, showed significant differences in the prestimulus total theta power between the normal and OCD groups. Taken together, frontal theta and occipital alpha oscillations seem to be potent electrophysiological correlates reflecting impairment in the prestimulus top-down processing of OCD patients.     

Brain event-related potential correlates of overfocused attention in obsessive-compulsive disorder

A hypothesis of overfocused attention in obsessive-compulsive disorder was investigated by measuring auditory event-related potentials (ERPs) during a selective attention task. Unmedicated patients (n= 18) with this disorder showed significantly larger attention-related processing negativity (PN), with earlier onset and longer duration, than did normal controls (n= 15). In the N200 region (160–250 ms), PN was larger in patients with fewer nonspecific neurological soft signs. This task, however, did not yield any group differences in mismatch negativity (N2a) or classical N200 (N2b). P300 amplitudes for attended targets were smaller for patient than normal groups, but the reverse was true for P300 and positive slow wave amplitudes for unattended nontargets. Collectively, these ERP abnormalities suggest a misallocation of cognitive resources. Because of the importance of the frontal lobe in the control of selective attention, PN enhancement in patients with obsessive-compulsive disorder may reflect hyperactivation of this region. This conceptualization is consistent with recent functional neuroimaging findings.     

Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: A preliminary voxel-based morphometry study

Neuroimaging studies have identified alterations in frontostriatal circuitry in obsessive-compulsive disorder (OCD). Voxel-based morphometry (VBM) allows for the assessment of differences in gray matter density across the whole brain. VBM has not previously been used to examine regional gray matter density in pediatric OCD patients and the siblings of pediatric OCD patients. Volumetric magnetic resonance imaging (MRI) studies were conducted in 10 psychotropic naïve pediatric patients with OCD, 10 unaffected siblings of pediatric patients with OCD, and 10 healthy controls. VBM analysis was conducted using SPM2. Statistical comparisons were performed with the general linear model, implementing small volume random field corrections for a priori regions of interest (anterior cingulate cortex or ACC, striatum and thalamus). VBM analysis revealed significantly lower gray matter density in OCD patients compared to healthy in the left ACC and bilateral medial superior frontal gyrus (SFG). Furthermore, a small volume correction was used to identify a significantly greater gray matter density in the right putamen in OCD patients as compared to unaffected siblings of OCD patients. These findings in patients, siblings, and healthy controls, although preliminary, suggest the presence of gray matter structural differences between affected subjects and healthy controls as well as between affected subjects and individuals at risk for OCD.     

构建大鼠内囊电毁损痉挛模型

目的：构建一种新的痉挛动物模型以期最大程度地模拟痉挛后的病理生理改变。方法：应用脑立体定位仪，精确地进行深部内囊的损伤定位，采用电毁损内囊的方式制造大鼠痉挛模型。结果：造模后痉挛组大鼠右上肢伸直的幅度与造模前痉挛组、造模前后空白组和假手术组比较明显降低，有统计学意义（P〈0.01）。结论：电毁损内囊可作为大鼠痉挛性瘫痪的一种优选方案。     

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.     

Metacognitive beliefs in obsessive-compulsive patients: A comparison with healthy and schizophrenia participants

Introduction. Distorted metacognitive beliefs are increasingly considered in theoretical models of obsessive-compulsive disorder (OCD). However, so far no consensus has emerged regarding the specific metacognitive profile of OCD.

Methods. Participants with OCD (n=55), schizophrenia (n=39), and nonclinical controls (n=49) were assessed with the Metacognitions Questionnaire (MCQ-30).

Results. Except for positive beliefs about worry, both patient samples exceeded nonclinical controls on all MCQ subscales. The MCQ “need to control thoughts” and “negative beliefs about uncontrollability and danger” subscales showed strong correlations with obsessions, and scores in the former scale were elevated in hallucinators. In contrast to several prior studies, “cognitive confidence” was related neither to core OCD nor to schizophrenia symptomatology.

Conclusions. Notwithstanding large pathogenetic differences between OCD and schizophrenia, findings suggest that obsessions and hallucinations may share a common metacognitive pathway. Need to control thoughts and dysfunctional beliefs about the malleability of worries may represent critical prerequisites for the two phenomena to emerge.